WO2014093626A1 - Compositions and methods for herbicide resistance - Google Patents

Abstract

The present disclosure provides compositions and methods for making and using carboxyl methyltransferase proteins capable of conferring plants with resistance to one or more auxin-like herbicides, such as dicamba, 2,4-dichlorophenoxyacetic acid (2,4-D), or both.

Description

COMPOSITIONS AND METHODS FOR HERBICIDE RESISTANCE

STATEMENT REGARDING SEQUENCE LISTING

The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is

200206_406WO_SEQUENCE_LISTING.txt. The text file is 229 KB, was created on December 9, 2013 and is being submitted electronically via EFS-Web.

BACKGROUND Technical Field

The present disclosure relates to compositions and methods for producing herbicide resistant plants and, more particularly, to altered nucleic acid molecules encoding methyltransferase proteins capable of conferring to plants resistance to one or more auxinic herbicides, such as dicamba, 2,4-dichlorophenoxyacetic acid, or both.

Description of the Related Art

Auxins are plant hormones involved in phototropism, geotropism,

hydrotropisim, and other developmental changes. In addition, auxins have a role in wound response, root growth and development, apical dominance, fruit growth and development, flowering and floral scent, and ethylene biosynthesis. On the molecular level, auxins include an aromatic ring and a carboxylic acid group, with the most prominent native member being indole-3 -acetic acid (IAA). Auxins are most active in broad leaf plants (dicots) as compared to narrow leaf plants (monocots). But, it was discovered that large concentrations of auxins are toxic to plants, so synthetic auxins have been developed as herbicides for weed control.

Herbicides are universally applied in modern agriculture to control weed growth in crop fields. The strategy for application of herbicides to kill weeds without harming crop plants is dependent on selective tolerance to a given herbicide by certain crop plants. In other words, the goal is to have crop plants survive application of the herbicide without significant ill effect, while weed plants do not. Another strategy is to develop crop plants having herbicide tolerance, which can be conferred by transgenic or mutagenic selection methods. For example, glyphosate, a broad-spectrum herbicide that inhibits aromatic amino acid synthesis, is now a very popular herbicide because several genetically engineered crops (including corn, soybean, canola, and cotton) have been developed to be resistant to glyphosate. Unfortunately, glyphosate resistant weeds are now developing along with an observed shift to weeds less sensitive to glyphosate.

One interesting aspect of synthetic auxin herbicide use is that no significant field resistance has developed, even though these auxin-like herbicides have been used for decades. One reason may be that synthetic auxin herbicides, like dicamba and

2,4-dichlorophenoxyacetic acid (2,4-D), do not persist in soil due to rapid plant uptake, volatilization, and microbial breakdown. For example, Pseudomonas maltophila was found to express a dicamba O-demethylase enzyme that rapidly converts dicamba into the non-herbicidal, non-toxic compound 3,6-dichlorosalicylic acid (DCS A) (see Wang et al., Appl. Enviro. Microbiol. 63:1623, 1997; Herman et al., J. Biol. Chem.

280:24759, 2005).

Nonetheless, as noted above, synthetic auxins tend to be more active against dicots than monocots, so several dicot crop plants (e.g., soybean, cotton, potatoes, tomatoes, fruit trees) are sensitive to the most common auxin herbicides (e.g., 2,4-D). Accordingly, this sensitivity limits the utility of auxin herbicides for controlling weeds in the cultivation of many dicot crop plants. Thus, there is a need for auxin herbicide tolerant crop plants.

BRIEF SUMMARY

In one aspect, the present disclosure provides altered nucleic acid molecules encoding carboxyl methyltransferase proteins specific for auxin- like herbicides. In another aspect, the present disclosure provides transgenic plants resistant to auxin-like herbicides having nucleic acid molecules encoding polypeptides having carboxyl methyltransferases with activity on synthetic auxin-like herbicides, such as dicamba, 2,4-D, or both.

In certain embodiments, provided herein is an isolated nucleic acid molecule encoding a polypeptide having carboxyl methyltransferase activity on auxin-like herbicides, wherein (a) the nucleic acid molecule comprises a polynucleotide sequence as set forth in SEQ ID NO:22 having at least one mutation that results in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (b) the nucleic acid molecule comprises at least 90% sequence identity with the polynucleotide sequence of (a); (c) the nucleic acid molecule encodes a polypeptide having carboxyl

methyltransferase activity and an amino acid sequence as set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (d) the nucleic acid molecule encodes a polypeptide comprising an amino acid sequence having carboxyl methyltransferase activity and at least 90% sequence identity with the polypeptide sequence set forth in SEQ ID NO:70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; or (e) a nucleic acid molecule that hybridizes under at least high stringency conditions with (i) a full length polynucleotide of any one or more of (a) through (d) or (ii) a full length complementary strand of (i).

These and other aspects of the present disclosure will become apparent upon reference to the following detailed description and attached drawings. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.

BRIEF DESCRIPTION OF THE DRAWINGS

Figures 1A - 1Y show exemplary nucleic acid molecules (SEQ ID NOS.: l-24 and 84) that encode various methyltransferase polypeptides, which can be modified to encode polypeptides having carboxyl methyltransferase activity against auxin-like herbicides.

Figures 2A - 2Y show the polypeptides (SEQ ID NOS.:49-72 and 83) encoded by the nucleic acid molecules of Figures 1A - 1Y.

Figures 3 A - 3X show the exemplary nucleic acid molecules of Figures 1A - IX having modified polynucleotide sequences to optimize expression in Agrobacterium (SEQ ID NOS.:25-48).

Figures 4A - 4X show the exemplary nucleic acid molecules of Figures 1A - IX having modified polynucleotide sequences to optimize expression in E.coli (SEQ ID NOS.:88-l l l). DETAILED DESCRIPTION

In one aspect, the present disclosure provides compositions and methods for generating a recombinant herbicide tolerant or resistant plant. A library of recombinant nucleic acid molecules encoding mutated Oryza sativa (rice) carboxyl methyltransferase polypeptides with altered enzymatic activity against at least one or more synthetic auxins {e.g., dicamba, 2,4-dichlorophenoxyacetic acid) are used to identify carboxyl methyltransferase polypeptides with desired characteristics. In certain embodiments, provided are nucleic acid molecules encoding carboxyl methyltransferase polypeptides having activity against a plurality of synthetic herbicides {e.g. , two to five herbicides) while having little or no activity on natural plant hormones {e.g., auxins, such as indole- 3 -acetic acid, indole-3 -butyric acid, 4-chloroindole-3 -acetic acid, 2-phenylacetic acid). Such nucleic acid molecules encoding polypeptides having carboxyl methyltransferase activity against synthetic auxin-like herbicides can be used to generate transgenic plants resistant to auxin-like herbicides, such as dicamba, 2,4-D, or both.

By way of background, synthetic auxin- like herbicides generally mimic auxin, a plant growth hormone. Synthetic auxins are sometimes referred to as growth regulators because they upset the natural hormone balance in plants, so they are used primarily to control broadleaf weeds in grass crops, pastures, and turf. Moreover, synthetic auxin herbicides cause injury because plants cannot readily control the concentration of synthetic auxins applied in relatively high doses like they can control natural auxin levels.

These herbicides are used in growing turfgrass to suppress difficult to manage perennial broadleaves, in forest management for controlling woody plants, to control certain aquatic weeds, and on non-cropland sites. For example, herbicides 2,4-D and 2-methyl-4-chlorophenoxyacetic acid (MCPA) were developed in 1942 in the United States and United Kingdom, respectively. These herbicides revolutionized weed control when they were introduced shortly after World War II and provided momentum for the development of the pesticide industry. Foliar application is the primary form of treatment since most synthetic auxins are readily absorbed through roots and foliage and are translocated in both the xylem and phloem. Death may not occur for several weeks, but injury symptoms show up on young growth almost immediately after application. Injury symptoms include stem and petiole twisting (epinasty), leaf malformations (parallel venation, leaf strapping, and cupping), undifferentiated cell masses and adventitous root formation on stems, and stunted root growth in broadleaf species, while grass plants exhibit rolled leaves (onion leafing), fused brace roots, leaning stems, and stalk brittleness.

The compositions and methods of this disclosure allow a person of skill in the art to generate, for example, commercially relevant herbicide resistant crop plants that can be grown in the presence of the most commonly used herbicides. Furthermore, this approach provides several advantages, including avoiding accumulation of volatile modified products, minimizing off-target effects since ester modifications are reversible in vivo, and use of modification rather than degradation of herbicides to avoid production of toxic side products {e.g., formic acid) harmful to the plant.

Prior to setting forth this disclosure in more detail, it may be helpful to an understanding thereof to provide definitions of certain terms to be used herein.

Additional definitions are set forth throughout this disclosure. In the present description, the terms "about" and "consisting essentially of mean ± 20% of the indicated range, value, or structure, unless otherwise indicated. In addition, any numerical ranges recited herein are to be understood to include any integer within that range and, where applicable (e.g., concentrations), fractions thereof, such as one tenth and one hundredth of an integer (unless otherwise indicated). It should be understood that the terms "a" and "an" as used herein refer to "one or more" of the enumerated components. The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. As used herein, the terms "include," "have" and "comprise" are used synonymously, which terms and variants thereof are intended to be construed as non- limiting.

As used herein, "nucleic acid" or "nucleic acid molecule" refers to any of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), oligonucleotides, fragments generated by the polymerase chain reaction (PCR), and fragments generated by any of ligation, scission, endonuclease action, and exonuclease action. In certain

embodiments, the nucleic acids of the present disclosure are produced by PCR. Nucleic acids may be composed of monomers that are naturally occurring nucleotides (such as deoxyribonucleotides and ribonucleotides), analogs of naturally occurring nucleotides (e.g., a-enantiomeric forms of naturally-occurring nucleotides), or a combination of both. Modified nucleotides can have modifications in sugar moieties or in pyrimidine or purine base moieties. Sugar modifications include, for example, replacement of one or more hydroxyl groups with halogens, alkyl groups, amines, and azido groups, or sugars can be functionalized as ethers or esters. Moreover, the entire sugar moiety may be replaced with sterically and electronically similar structures, such as aza-sugars and carbocyclic sugar analogs. Examples of modifications in a base moiety include alkylated purines and pyrimidines, acylated purines or pyrimidines, or other well- known heterocyclic substitutes. Nucleic acid monomers can be linked by

phosphodiester bonds or analogs of such linkages. Analogs of phosphodiester linkages include phosphorothioate, phosphorodithioate, phosphoroselenoate,

phosphorodiselenoate, phosphoroanilothioate, phosphoranilidate, phosphoramidate, and the like. The term "nucleic acid molecule" also includes so-called "peptide nucleic acids" (PNAs), which comprise naturally occurring or modified nucleic acid bases attached to a polyamide backbone. Nucleic acid molecules can be either single stranded or double stranded.

Further, an "isolated nucleic acid molecule" refers to a polynucleotide molecule in the form of a separate fragment or as a component of a larger nucleic acid construct, which has been separated from its source cell (including the chromosome it normally resides in) at least once in a substantially pure form. For example, a DNA molecule that encodes a recombinant polypeptide, peptide, or variant thereof, which has been separated from a cell or from the genomic DNA of a cell, is an isolated nucleic acid molecule. Another example of an isolated nucleic acid molecule is a bacteriophage promoter (e.g., T5 or T7), or nucleic acid expression control sequence, which can be cloned into a vector capable of replication in a suitable host cell. Still another example of an isolated nucleic acid molecule is a chemically synthesized or PCR synthesized nucleic acid molecule.

As used herein, "mutation" refers to a change in the sequence of a nucleic acid molecule or polypeptide molecule as compared to a reference or wild-type nucleic acid molecule or polypeptide molecule, respectively. A mutation can result in several different types of change in sequence, including substitution, insertion or deletion of nucleotide(s) or amino acid(s). In certain embodiments, a mutation is a deletion of one or more nucleotides or residues. In other embodiments, a mutation is an insertion or substitution of one or more nucleotides or residues. A nucleic acid molecule mutation may also include rearrangements of large segments of nucleotides, such as

chromosomal translocations, inversions, or duplications.

As used herein, a "nucleic acid molecule library" refers to a collection of nucleic acid molecule sequences or fragments that are incorporated into a vector, which may be transformed or transfected into an appropriate host cell. The target nucleic acid molecules of this disclosure may be introduced into a variety of different vector backbones (such as plasmids, cosmids, viral vectors, or the like) so that recombinant production of a nucleic acid molecule library can be maintained in a host cell of choice (such as bacteria, yeast, mammalian cells, plant cells, or the like). The nucleic acid molecules that are incorporated into a vector may be from natural samples (e.g., a genome), or the nucleic acid molecules may be synthetic samples (e.g., PCR product), recombinant samples, or a combination thereof. Prior to insertion into a vector, a plurality of nucleic acid molecules may undergo additional reactions for optimal cloning, such as mechanical shearing, specific cleavage with restriction endonucleases, or addition of short nucleotide sequences to introduce, for example, a restriction endonuclease site.

For example, a collection of nucleic acid molecules representing an entire genome is called a genomic library. Methods for construction of nucleic acid molecule libraries are well known in the art (see, e.g., Ausubel et al., Short Protocols in

Molecular Biology, 5th ed., Wiley & Sons, 2002; Sambrook et al., Molecular Cloning: A Laboratory Manual, Third Edition, Cold Spring Harbor, N.Y., 2001; Gubler, Methods in Enzymology, Vol. 152, Guide to Molecular Cloning Techniques, Berger and Kimmel,

Eds., San Diego: Academic Press, Inc., 1987).

As used herein, the term "polypeptide library" refers to a collection of different polypeptides that are different to one another although some level of redundancy may be present. A library may contain a plurality of different polypeptide members, wherein the term "plurality" refers to at least 2, at least 5, at least 10, at least 50, at least

10, at least 100, at least 200, at least 500, at least 1,000 or more, up to 1,000 or more.

The members of a library may be interspersed with one another, in which case they may form a mixture. In other cases, the different members of a library may be spatially separated from one another, e.g., in different vessels such as in different wells of a multi-well plate. For example, polypeptides of a library may be made be expressed from a nucleic acid molecule library.

As used herein, a "nucleic acid molecule primer" or "primer" and variants thereof refers to short nucleic acid sequences that a DNA polymerase can use to begin synthesizing a complementary DNA strand of the molecule bound by the primer. A primer sequence can vary in length from 5 nucleotides to about 50 nucleotides in length, from about 10 nucleotides to about 35 nucleotides, and preferably are about 15,

16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35

nucleotides in length. In certain embodiments, a nucleic acid molecule primer that is complementary to a target nucleic acid of interest can be used to initiate an

amplification reaction, a sequencing reaction, or both.

The term "construct" refers to any polynucleotide that contains a recombinant nucleic acid. A construct may be present in a vector {e.g., a bacterial vector, a viral vector) or may be integrated in a genome, for example. A "vector" is a nucleic acid molecule that is capable of transporting another nucleic acid. Vectors may be, for example, plasmids, cosmids, viruses, or phage.

The term "operably-linked" refers to the association of nucleic acid sequences on a single nucleic acid fragment so that the function of one is affected by the other.

For example, a promoter is operably-linked with a coding sequence when it is capable of affecting the expression of that coding sequence (i.e., the coding sequence is under the transcriptional control of the promoter). "Unlinked" means that the associated genetic elements are not closely associated with one another and the function of one does not affect the other.

As used herein, "expression vector" refers to a DNA construct containing a nucleic acid molecule that is operably-linked to a suitable control sequence capable of effecting the expression of the nucleic acid molecule in a suitable host. Such control sequences include a promoter to effect transcription, an optional operator sequence to control such transcription, a sequence encoding suitable mR A ribosome binding sites, and sequences which control termination of transcription and translation. The vector may be a plasmid, a phage particle, or simply a potential genomic insert. Once transformed into a suitable host, the vector may replicate and function independently of the host genome, or may, in some instances, integrate into the genome itself. In the present specification, "plasmid," "expression plasmid," and "vector" are often used interchangeably as the plasmid is the most commonly used form of vector at present. However, this disclosure is intended to include such other forms of expression vectors that serve equivalent functions and which are, or become, known in the art.

The term "expression", as used herein, refers to the process by which a polypeptide is produced based on the nucleic acid sequence of a gene. The process includes both transcription and translation.

The term "introduced" in the context of inserting a nucleic acid sequence into a cell, means "transfection", or 'transformation" or "transduction" and includes reference to the incorporation of a nucleic acid sequence into a eukaryotic or prokaryotic cell wherein the nucleic acid sequence may be incorporated into the genome of the cell (e.g., chromosome, plasmid, plastid, or mitochondrial DNA), converted into an autonomous replicon, or transiently expressed (e.g., transfected mRNA).

The term "selective marker" refers to a protein capable of expression in a host that allows for ease of selection of those hosts containing and expressing an introduced nucleic acid molecule or vector. Examples of selectable markers include proteins that confer resistance to antimicrobial agents (e.g., hygromycin, kanamycin, bleomycin, or chloramphenicol), proteins that confer a metabolic advantage, such as a nutritional advantage on the host cell, as well as proteins that confer a functional or phenotypic advantage (e.g., cell division) on a cell.

The term "contacting" means to bring or put together. As such, a first item is contacted with a second item when the two items are brought or put together, e.g., by touching them to each other or combining them in the same solution.

As used herein, "wild-type", "native" or "naturally-occurring" refers to proteins are those found in nature. The term "wild-type sequence" or "reference sequence" is used herein to refer to a sequence that is native or naturally occurring in a host cell. The term "non-naturally occurring" or "mutant" refers to proteins that are not found in nature.

As used herein, the term "isolated" refers to a substance that has been removed from the source in which it naturally occurs. A substance need not be purified in order to be isolated. For example, a protein produced in a host cell is considered isolated when it is removed or released from the cell. A protein contained within a crude cell lysate fraction is considered "isolated" for purposes of the present disclosure. Further, an "isolated nucleic acid molecule" refers to a polynucleotide molecule in the form of a separate fragment or as a component of a larger nucleic acid construct, which has been separated from its source cell, including the chromosome it normally resides in, at least once. For example, a DNA molecule that encodes a recombinant polypeptide, peptide, or variant thereof, which has been separated from the genomic DNA of a cell, is an isolated DNA molecule.

As used herein, the term "purified" refers to a substance that has been rendered at least partially free of contaminants and other materials that typically accompany it. Substances can be purified to varying degrees. A substance is "substantially pure" when a preparation or composition of the substance contains less than about 1% contaminants. A substance is "essentially pure" when a preparation or composition of the substance contains less than about 5% contaminants. A substance is "pure" when a preparation or composition of the substance contains less than about 2% contaminants. For substances that are "purified to homogeneity," contaminants cannot be detected with conventional analytical methods.

The term "recombinant" refers to a polynucleotide or polypeptide that does not naturally occur in a host cell. A recombinant molecule may contain two or more naturally-occurring sequences that are linked together in a way that does not occur naturally. A recombinant cell contains a recombinant polynucleotide or polypeptide.

The term "heterologous" refers to elements that are not normally associated with each other. For example, if a host cell produces a heterologous protein, then that protein that is not normally produced in that host cell is heterologous. Likewise, a promoter that is operably-linked to a heterologous coding sequence is a promoter that is operably-linked to a coding sequence that it is not usually operably-linked to in a wild- type host cell. The term "endogenous," with reference to a polynucleotide or protein, refers to a polynucleotide or protein that occurs naturally in a host cell.

As used herein, the terms "percent sequence identity," "percent identity," and

"% identity" refer to comparisons between polynucleotide sequences or polypeptide sequences, and are determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence in order to effect optimal alignment. Percent identity is calculated by dividing the number of matched portions in the comparison window by the total number of positions in the comparison window, and multiplying by 100. The number of matched positions in the comparison window is the sum of the number of positions of the comparison polynucleotide or polypeptide in the window that are identical in sequence to the reference polynucleotide or polypeptide and the number of positions of the reference polynucleotide or polypeptide in the comparison window that align with a gap in the comparison polynucleotide or polypeptide. Determination of optimal alignment and percent sequence identity is performed using the BLAST and BLAST 2.0 algorithms (see, e.g., Altschul et al., J. Mol. Biol. 275:403, 1990; Altschul et al., Nucleic Acids Res. 25:3389, 1997). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information website.

Briefly, the BLAST analyses involve first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., 1990, supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score.

Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11 , an expectation (E) of 10, M=5, N=-4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength (W) of 3, an

expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff, Proc. Nat'l Acad. Sci. USA SM0915, 1989). In a preferred embodiment, BLAST algorithm parameters set a default parameters are used to identify percent identity of a target nucleic acid molecule or a target polypeptide molecule as compared to a reference nucleic acid molecule or a reference polypeptide molecule, respectively.

Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman, Adv. Appl. Math. 2:482, 1981; by the homology alignment algorithm of Needleman and Wunsch, J. Mol. Biol. 48:443, 1970; by the search for similarity method of Pearson and Lipman, Proc. Nat'l Acad. Sci. USA 85:2444, 1988; by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the GCG Wisconsin Software Package); or by visual inspection (see, generally, Current Protocols in Molecular Biology, F. M.

Ausubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., 1995 Supplement).

As used herein, the term "reference sequence" refers to a specified sequence to which another sequence is compared. A reference sequence may be a subset of a larger sequence, for example, a segment of a full-length gene or polypeptide sequence.

Generally, a reference sequence is at least 20 nucleotide or amino acid residues in length, at least 25 residues in length, at least 50 residues in length, or the full length of the nucleic acid or polypeptide. Since two polynucleotides or polypeptides may each (1) comprise a sequence (i.e., a portion of the complete sequence) that is similar between the two sequences, and (2) may further comprise a sequence that is divergent between the two sequences, sequence comparisons between two (or more)

polynucleotides or polypeptide are typically performed by comparing sequences of the two polynucleotides over a comparison window to identify and compare local regions of sequence similarity. The term "reference sequence" is not intended to be limited to wild-type sequences, and can include engineered, variant, or altered sequences.

As used herein, the phrase "amino acid substitution" or "substitution mutation" refers to the replacement of a first amino acid with any other amino acid. In certain embodiments, a "conservative amino acid substitution" refers to the replacement of a first amino acid with a second amino acid having the same properties as the first amino acid. Such groupings of amino acids are defined herein.

For example, a "hydrophilic amino acid residue" is an amino acid having a side chain exhibiting a hydrophobicity of less than zero according to the normalized consensus hydrophobicity scale of Eisenberg et al., J. Mol. Biol. 179:125, 1984.

Genetically encoded hydrophilic amino acids include Thr (T), Ser (S), His (H), Glu (E), Asn (N), Gin (Q), Asp (D), Lys (K) and Arg (R). A "hydrophobic amino acid residue" is an amino acid having a side chain exhibiting a hydrophobicity of greater than zero according to the normalized consensus hydrophobicity scale of Eisenberg et al., J. Mol. Biol. 179:125, 1984. Genetically encoded hydrophobic amino acids include Pro (P), He (I), Phe (F), Val (V), Leu (L), Trp (W), Met (M), Ala (A) and Tyr (Y). An "aromatic amino acid residue" is a hydrophilic or hydrophobic amino acid having a side chain that includes at least one aromatic or heteroaromatic ring. Genetically encoded aromatic amino acids include Phe (F), Tyr (Y) and Trp (W). Owing to the pKa of its

heteroaromatic ring nitrogen, His (H) is classified herein as a hydrophobic or basic residue. It is additionally classified as an aromatic residue due to its heteroaromatic side chain. An "aliphatic amino acid residue" is a hydrophobic amino acid or residue having an aliphatic hydrocarbon side chain. Genetically encoded aliphatic amino acids include Ala (A), Val (V), Leu (L) and lie (I).

An "acidic amino acid residue" is a hydrophilic amino acid having a side chain exhibiting a pKa value of less than about 6 when the amino acid is included in a peptide or polypeptide. Acidic amino acids typically have negatively charged side chains at physiological pH due to loss of a hydrogen ion. Genetically encoded acidic amino acids include Glu (E) and Asp (D). A "basic amino acid residue" is a hydrophilic amino acid or residue having a side chain exhibiting a pKa value of greater than about 6 when the amino acid is included in a peptide or polypeptide. Basic amino acids typically have positively charged side chains at physiological pH due to association with hydronium ion. Genetically encoded basic amino acids include Arg (R), His (H) and Lys (K).

A "polar amino acid residue" is a hydrophilic amino acid having a side chain that is uncharged at physiological pH, but which has at least one bond in which the pair of electrons shared in common by two atoms is held more closely by one of the atoms. Genetically encoded polar amino acids include Asn (N), Gin (Q), Ser (S) and Thr (T). A "non-polar amino acid residue" is a hydrophobic amino acid having a side chain that is uncharged at physiological pH and which has bonds in which the pair of electrons shared in common by two atoms is generally held equally by each of the two atoms (i.e., the side chain is not polar). Genetically encoded non-polar amino acids include Gly (G), Leu (L), Val (V), lie (I), Met (M) and Ala (A).

A cysteine is unusual in that it can form disulfide bridges with other Cys residues or other sulfanyl- or sulfhydryl-containing amino acids. "Cysteine-like residues" include cysteine and other amino acids that contain sulfhydryl moieties that are available for formation of disulfide bridges. The ability of Cys (and other amino acids with -SH containing side chains) to exist in a polypeptide in either the reduced free -SH or oxidized disulfide-bridged form affects whether it contributes net hydrophobic or hydrophilic character to the polypeptide. While Cys exhibits a hydrophobicity of 0.29 according to the normalized consensus scale of Eisenberg (Eisenberg et al., 1984, supra), it is to be understood that for purposes of the present disclosure, Cys is categorized into its own unique group. A "small amino acid residue" is an amino acid having a side chain that is composed of a total of three or fewer carbon or heteroatoms (excluding the . alpha. - carbon and hydrogens). The small amino acids or residues may be further categorized as aliphatic, non-polar, polar or acidic small amino acids or residues, in accordance with the above definitions. Genetically-encoded small amino acids include Ala (A), Val (V), Cys (C), Asn (N), Ser (S), Thr (T) and Asp (D).

A "hydroxyl-containing amino acid residue" is an amino acid containing a hydroxyl (-OH) moiety. Genetically-encoded hydroxyl-containing amino acids include Ser (S) Thr (T) and Tyr (Y).

As used herein, the term "herbicide" refers to a compound that controls (kills or slows the growth of) one or more plants, e.g., a weed. Generally, an herbicide is lethal to a susceptible plant. Herbicides can be selective in that they control the growth of one plant {e.g., a weed) while simultaneously allowing the growth of another {e.g., a crop), or broad spectrum where they control the growth of a wide variety of plants. The term "auxin- like herbicide" refers to compounds that have an aromatic ring and a carboxylic acid group that are generally synthetic, but do not correspond to one of the naturally occurring auxins of indole-3 -acetic acid, indole-3 -butyric acid, 4-chloroindole-3 -acetic acid, and 2-phenylacetic acid. "Natural plant hormones" are chemicals produced in small quantities by plants that affect or regulate plant growth, which include many low molecular weight metabolites, such as indole-3 -acetic acid (IAA), gibberellic acid

(GA), salicylic acid (SA), jasmonic acid (JA), or other auxins. Furthermore, plants may have enzymes that chemically modify such metabolites {e.g., methyltransferases) and such changes may drastically alter their biological or ecological functions (or may possibly function differently from the parent compound).

As used herein, the term "herbicide tolerance" or "herbicide resistance" refers to the ability of a plant to survive and reproduce following exposure to a dose of herbicide that would normally be lethal to the wild-type plant.

Libraries and Screening Assays

As noted herein, a library of variant carboxyl methyltransferase (MT) proteins is provided. In certain embodiments, a library comprises at least 10 different MT proteins, e.g., at least 15, at least 20, at least 40, at least 80, at least 100, at least 200, at least 500 or at least 1,000 or more different MT proteins. In particular embodiments, a library may have a limited number of members, e.g., up to 96, 192 or 384 members, although larger libraries are also envisioned. Each MT protein of a library is a polypeptide that is at least 90% identical {e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to a reference or parental wild-type MT protein. In certain embodiments, members of the library also contain at least one amino acid substitution (e.g., 1 , 2, 3, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15 or more or up to about 20, about 25, about 30, about 35 or about 40 substitutions) at a pre-determined position or positions relative to a reference or parental wild-type MT protein, provided that the variant retains carboxyl methyltransferase activity or at least one carboxyl methyltransferase antigenic epitope. In particular embodiments, altered MT polypeptides have at least one to about 10, about 1 1 , about 12, about 13, about 14, or about 15 amino acid substitutions at predetermined positions, as shown in Table 1.

Table 1. Exemplary MT Amino Acid Substitution Positions

As used herein, the term "pre-determined position" refers to a position that is defined beforehand. In the context of a variant polypeptide that has an amino acid substitution at a pre-determined position relative to a reference or parent protein, the variant protein contains an amino acid residue at a position that was identified in the parent protein before the substitution was made. For example, site-directed

mutagenesis may be performed at predetermined positions by substituting an amino acid for a different amino acid, wherein the different amino acid may be selected from any of the plurality of amino acids provided in this disclosure or known in the art (e.g. , a conservative substitution, each of the natural amino acids, non-natural amino acids). In certain embodiments, site-directed mutations may be incorporated by synthesizing a mutated nucleic acid molecule with one more mutations at pre-determined positions, such as at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22.

For clarity and unless otherwise indicated, all enumerated amino acid positions in this disclosure (e.g., those in Tables 1-4) are with reference to SEQ ID NO:70, a 375 amino acid MT polypeptide sequence (from rice Oryza sativa subspecies indica;

GenBank Accession No. EAY92873.1). In certain embodiments, a polypeptide as set forth in SEQ ID NO:70 is encoded by a nucleic acid molecule having a polynucleotide sequence as set forth in SEQ ID NO:22. Similarly, all enumerated nucleotide positions of nucleic acid molecules in this disclosure are with reference to SEQ ID NO:22 (from rice O. sativa subsp. indica, located at cl607620-1607546, cl607227-1606811, cl606704-1606441, cl605687-1605316 on chromosome 4, whole genome shotgun sequence; from GenBank Accession No. CM000129.1 for chromosome 4), a 1,125 polynucleotide sequence that encodes for a (wild-type or reference) MT polypeptide of this disclosure.

Equivalent amino acid positions found in similar MT sequences, including homologs, orthologs, paralogs, or the like, can be identified by sequence alignment with SEQ ID NO:70, as described herein. If a carboxyl methyltransferase polypeptide of this disclosure is indicated as having a substitution selected from one or more Tables, e.g., Table 2 (as may be indicated by the phrase "amino acid substitutions are selected from those listed in Table 2" or a grammatical equivalent thereof), the protein has one or more substitutions at the positions that correspond to the positions identified in the Table(s). For example, if a protein is described as having the following amino acid substitutions "G245A / M160H" (see Table 4), the protein will have an alanine residue at the position that corresponds to position 245 in SEQ ID NO:70 and a histidine at the position that corresponds to position 160 in SEQ ID NO: 70. If a protein is described as having a conservative amino acid substitution of a substitution of G245A / M160H, then the protein may have, for example, a valine or leucine at the position that corresponds to position 245 in SEQ ID NO: 70 and an arginine or lysine at the position that corresponds to position 160 in SEQ ID NO:70.

In certain embodiments, altered MT proteins of the present disclosure have at least one amino acid substitution at a predetermined position as shown by underline and bold in Table 1. In still further embodiments, each substitution may be present in more than one MT protein of a library. For example, if a library contains up to 96 members, any one substitution may be present in more than one member (e.g., in 2, 3, 4, 5, or 6 or up to 10 or more members). In particular embodiments, substitutions may be distributed throughout a library, such that each member of a library contains multiple substitutions, wherein each substitution may be present in several members of the library.

In certain embodiments, the identity and position of the amino acid being substituted may be selected from Table 2, e.g., at the positions identified in bold and underline. In particular embodiments, amino acid substitutions may be independently selected from Table 2 or may be conservative amino acid substitutions thereof.

Table 2. Exemplary MT Amino Acid Substitutions

Position Position Position Position Position Position

T248D S109G A189H F267Y V150L C44F

L284S I290L A189Y E71N F68P C44Y

N350K I290M N194R E252Q N148R I3L

N350R L330M N194S 1367V K361R I3M

F132L H131C LI 69V A31M Q280E

I287L A189G K225D A31 S Q280R

V36I Q193K K225S F93A K225E

In certain embodiments, members of a library may be mixed or spatially separated from one another. If members of a library are spatially separated, then they may be in or on a substrate, such as a multi-well plate in a form that is suitable for performing an assay as described herein. For example, in certain embodiments, individual members of a library may be present in wells of any number (1, 2, 3, 4, 5 or more) of 48 well plates, 96 well plates, 384 well plates, or plates having other numbers of wells. The proteins may be present in cells (e.g., bacterial cells) or in a cell-free environment in the form of a lysate or a purified protein or fusion protein.

Appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are described, for example, by Sambrook et al., Molecular Cloning: A Laboratory Manual, Third Edition, Cold Spring Harbor, NY, (2001), and may include plasmids, cosmids, shuttle vectors, viral vectors and vectors comprising a chromosomal origin of replication as disclosed therein (e.g., yeast artificial chromosome or YAC). Generally, nucleic acid expression vectors include origins of replication and selectable markers permitting detectable transformation of the host cell (e.g., ampicillin resistance gene of E. coli, S. cerevisiae TRPT gene) and an expression control sequence such as a promoter. In addition, a heterologous structural sequence may be included in appropriate phase with translation initiation sequences and termination sequences of the vector.

Optionally, a heterologous sequence can encode a fusion protein including an amino-terminal (or a carboxy-terminal) identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product. For example, a tag allows for isolation or selection that is independent of the tagged partner molecule's structure or sequence. Tag molecules may be attached, for example, by using genetic methods, by synthetically including in the sequence, or by chemically coupling. Tag molecules are well known in the art and include, e.g., biotin, HIS tag, Flag® epitope, GST, chitin binding protein, maltose binding protein. In certain embodiments, for example, recombinant polypeptides are fused in-frame to a carboxy-terminal tag, which tag may be any one of alkaline phosphatase, β-galactosidase, hexahistidine (6xHis), GST, or the like. In certain embodiments, for example, recombinant polypeptides are synthesized with an in-frame carboxy-terminal tag, such as alkaline phosphatase, β-galactosidase, hexahistidine (6xHis), GST, or the like. In a particular embodiment, the carboxy-terminal tag is GHHHHHH (SEQ ID NO:87). Recombinant fusion proteins that facilitate affinity detection and isolation of the hybrid polypeptides are preferred and may include, for example, poly-His or the defined antigenic peptide epitopes described in U.S. Patent No. 5,011,912 and in Hopp et al, (Bio/Technology (5: 1204, 1988), or the XPRESS™ epitope tag (Invitrogen, Carlsbad, CA). An affinity sequence may be a hexa-histidine tag as supplied by a vector, such as, for example, pBAD/His (Invitrogen). Alternatively, an affinity sequence may be added either synthetically or engineered into the primers used to recombinantly generate a nucleic acid molecule coding sequence {e.g. , using polymerase chain reaction). Preferably, a recombinant polypeptide is fused to or synthesized with a polyhistidine and is encoded by a recombinant nucleic acid molecule capable of encoding or expressing such a fusion protein.

Expression constructs for bacterial use may be made by inserting into an expression vector a structural DNA sequence encoding a desired protein together with a nucleic acid expression control sequence as described herein. A construct may comprise one or more phenotypic selectable markers and an origin of replication to ensure maintenance of the vector construct and, if desirable, to provide amplification within the host. Suitable prokaryotic hosts for transformation include Escherichia coli, Agrobacterium tumefaciens, Bacillus subtilis, Salmonella typhimurium, or various species within the genera Pseudomonas, Streptomyces, or Staphylococcus, although others may also be employed as a matter of choice. Any other plasmid or vector may be used as long as they are replicable and viable in the host cell.

As a representative example, expression vectors for bacterial use can comprise a selectable marker and bacterial origin of replication derived from commercially available plasmids comprising genetic elements of the well known cloning vector pBR322 (ATCC 37017). Such commercial vectors include, for example, pGEM vectors (Promega Corp., Madison, WI, USA), pJExpress vectors (DNA 2.0, Menlo Park, CA, USA), and the T7 pET vectors (EMD Millipore (Merck), Billerica, MA, USA). These pBR322 "backbone" sections may be combined with an appropriate nucleic acid expression control sequence and a structural sequence of the present disclosure that is to be expressed. The pBR322 replication origin is considered medium copy in that bacteria produce about 20-80 copies of the plasmid per cell. Low-copy vectors, such as those based on pSClOl, pBR322-rop or pACYC, may also be used (e.g., pACYC-based pJExpress vectors from DNA 2.0, Menlo Park, CA, USA). High copy vectors, such those based on the pUC plasmids, may also be used (e.g., pUC-based pJExpress vectors from DNA 2.0, Menlo Park, CA, USA).

Other vectors and constructs include chromosomal, non-chromosomal and synthetic DNA sequences, e.g., derivatives of SV40; bacterial plasmids; phage DNA; baculovirus; yeast plasmids; yeast artificial chromosomes (YACs); vectors derived from combinations of plasmids and phage DNA; shuttle vectors derived from combinations of plasmids and viral DNA; viral DNA, such as vaccinia, adenovirus, fowl pox virus, and pseudorabies. However, any other vector may be used for preparation of a nucleic acid molecule expression construct as long as it is replicable and viable in the host cell of interest. Further, in some embodiments, nucleic acid expression constructs containing the nucleic acid expression control sequence operably- linked to polynucleotide coding sequence(s) for polypeptide(s) and fusion protein(s) may remain extrachromosomal, and in another preferred embodiments the expression constructs may integrate at least once or into at least one host cell chromosome.

In certain embodiments, the nucleic acid expression construct has a second expression control sequence, such as a promoter, which may be lac, lac\JV5, tac, trc, ara, trp, λ phage, T3 phage promoter, and T7 phage promoter. An "expression control sequence" refers to any sequence sufficient to allow expression of a protein of interest in a host cell, including one or more promoter sequences, enhancer sequences, operator sequences (e.g., lacO), or the like. In certain embodiments, a nucleic acid expression control sequence is in a plasmid and the host cell is a bacterium, such as Escherichia coli. In further embodiments, a second expression control sequence may be an

"externally regulated promoter," which includes functional promoter sequences having activity that may be altered (e.g., increased or decreased) by an additional element, agent, molecule, component, co-factor, or the like. An externally regulated promoter may comprise, for example, a repressor binding site, an activator binding site or any other regulatory sequence that controls expression of a polynucleotide sequence as provided herein. In certain embodiments, an externally regulated promoter is a tightly regulated promoter that is specifically inducible and permits little or no transcription of polynucleotide sequences under its control in the absence of an induction signal, as is known to those familiar with the art and described, for example, in Guzman et al. (J. Bacteriol. 177:4121, 1995), Carra et al. (EMBO J. 12:35, 1993), Mayer (Gene 163:41, 1995), Haldimann et al. (J. Bacteriol. 180: 1277, 1998), Lutz et al. (Nucleic Acids Res., 25: 1203, 1997), Allgood et al. (Curr. Opin. Biotechnol. 8:474, 1997), or Makrides (Microbiol. Rev. 60:512, 1996). In other embodiments of the present disclosure, a second externally regulated promoter is present that is inducible but may not be tightly regulated. In certain other embodiments, a second promoter is present in an expression construct of the present disclosure that is not a regulated promoter; such a promoter may include, for example, a constitutive promoter such as an insect polyhedrin promoter or a yeast phosphoglycerate kinase promoter (see, e.g., Giraud et al., J. Mol. Biol. 281 :409, 1998). A nucleic acid expression construct may also contain a transcription terminator or appropriate sequences for amplifying expression.

Transcription of a nucleic acid molecule encoding a polypeptide by higher eukaryotes may be increased by inserting an enhancer sequence into the vector.

Enhancers are czs-acting elements of DNA, usually ranging in size from about 10 nucleotides to about 300 nucleotides, which act on a promoter to increase transcription. Examples include an SV40 enhancer on the late side of the replication origin nucleotides 100 to 270, a cytomegalovirus early promoter enhancer, a polyoma enhancer on the late side of the replication origin, adenovirus enhancers, or any combination thereof.

As noted herein, in certain embodiments, a vector may be a viral vector such as a retroviral vector. For example, retroviruses, from which a retroviral plasmid vector may be made or derived, include Moloney Murine Leukemia Virus, spleen necrosis virus, retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma virus, avian leukosis virus, gibbon ape leukemia virus, human immunodeficiency virus, adenovirus, Myeloproliferative Sarcoma Virus, or mammary tumor virus.

In certain embodiments, a vector comprises a nucleic acid molecule encoding a polypeptide having carboxyl methyltransferase activity on herbicides, such as auxinlike herbicides, wherein (a) the nucleic acid molecule comprises a polynucleotide sequence as set forth in SEQ ID NO:22 having at least one mutation that results in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (b) the nucleic acid molecule comprises at least 90% sequence identity with the polynucleotide sequence of (a); (c) the nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity and an amino acid sequence as set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (d) the nucleic acid molecule encodes a polypeptide comprising an amino acid sequence having carboxyl methyltransferase activity and at least 90%> sequence identity with the polypeptide sequence set forth in SEQ ID NO:70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; or (e) a nucleic acid molecule that hybridizes under at least high stringency conditions with (i) a full length polynucleotide of any one or more of (a) through (d) or (ii) a full length complementary strand of (i).

In further embodiments, a vector comprises (a) a nucleic acid molecule having a mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any

combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids; or (b) a nucleic acid molecule having a mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids and the polynucleotide sequence of SEQ ID NO:22 further comprises mutations that result in 1 to about 20 additional amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; and wherein each mutated nucleic acid molecule preferably encodes a polypeptide with (i) carboxyl methyltransferase activity on an herbicide, preferably two herbicides (such as dicamba and 2,4-D), and (ii) minimal or no activity on a plant hormone such as salicylic acid.

In still further embodiments, a vector encoded MT polypeptide comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the polypeptide sequence set forth in SEQ ID NO:70; or an encoded MT polypeptide comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70 and the polypeptide sequence of SEQ ID NO: 70 further comprises from 1 to about 20 additional substitution mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4, and each encoded MT polypeptide preferably has carboxyl

methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid.

In certain embodiments, provided herein is a vector comprising a nucleic acid molecule encoding a polypeptide having carboxyl methyltransferase activity, wherein (a) the nucleic acid molecule comprises a polynucleotide sequence having at least 90% sequence identity with the polynucleotide sequence as set forth in SEQ ID NO:22 having at least one mutation that results in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4, provided that the polynucleotide having at least 90% sequence identity does not have a change that alters the at least one mutation that results in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; or (b) the nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-D, minimal or no activity on salicylic acid, and an amino acid sequence having at least 90% sequence identity with the polypeptide sequence set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4, provided that the 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4 are not altered. In certain embodiments, the aforementioned vectors comprise a nucleic acid molecule further comprising a mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of an encoded amino acid or amino acids, and preferably such mutant nucleic acid molecules encode a polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-D with minimal or no activity on salicylic acid. In certain other embodiments, the aforementioned encoded MT polypeptides further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70, and preferably such mutant polypeptides have carboxyl methyltransferase activity on dicamba and 2,4- D, and minimal or no activity on salicylic acid.

In further embodiments, any of the aforementioned vectors contain a nucleic acid molecule that encodes an MT polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid, benzoic acid, indole-3 -acetic acid, or any combination thereof. In still further embodiments, any of the aforementioned vectors are an expression vector. In yet further embodiments, provided are a recombinant host cells comprising any of the aforementioned vectors or a nucleic acid molecule encoding an MT polypeptide of this disclosure. In certain preferred embodiments, a recombinant host cell is a plant cell.

In certain embodiments and as noted herein, MT proteins may each comprise at least 2 amino acid substitutions relative to the parental wild type MT protein. In particular embodiments, amino acid substitutions may be at residues corresponding to positions listed in Table 3. In further embodiments, amino acid substitutions may be selected from those shown in Table 4, or conservative amino acid substitutions of the substitutions as listed in Table 4.

A library of polynucleotides that encode the library of MT proteins is also provided, as well as nucleic acid constructs containing the same. The constructs may be designed to express the encoded protein when introduced into a host cell and, as such, may contain an expression cassette containing the polynucleotides of the present disclosure. A host cell may be any suitable cell, such as a bacterial cell, yeast cell, or eukaryotic cell.

Also provided are screening methods that make use of the library of MT polypeptides described herein. In general terms, this method may involve screening an auxin-like herbicide against a MT protein library to identify MT polypeptides that have an increased ability to methylate one, two, three, four, five, or more selected herbicides (wherein the term "increased" encompasses a new activity, as well as any activity that is increased from a detectable level as compared to a reference or parent wild-type MT). Alternatively, or in combination with above noted method, the method may involve screening a MT library against native plant auxins (e.g., salicylic acid) to identify MT polypeptides that have a reduced ability to methylate one, two, three, four, or more selected hormones (wherein the term "reduced" encompasses elimination of any methylation activity below the level of detection in a methyltransferase assay as described herein, as well as ensuring that no new activity against a hormone is detected in a library of variants). Preferably, methylation of selected auxin-like herbicides inactivates the herbicidal activity of the target herbicide. These methods may, in certain cases, involve obtaining a the library described herein, individually contacting a selected auxin-like herbicide or hormone with each MT protein of the library in the presence of S-adenosyl-L-methionine (SAM); and assaying for methylation of the selected herbicide or hormone (i.e., methylation will reduce or inactivate biological activity).

In particular embodiments, the level of methylation is quantitatively measured to provide a numerical read-out that allows the various results to be compared to one another. An MT polypeptide that has an increased ability to methylate a selected herbicide is one that has at least two-fold more activity (in terms of the amount of SAM used in a period of time) relative to reference or wild-type parental MT. In some embodiments, such a carboxyl methyltransferase of the present disclosure may have about 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold or 1,000-fold or more activity than a reference or wild-type parental MT.

A number of SAM-based methyltransferase (AdoMet) assay kits are

commercially available (see, e.g., Methyltransferase Activity Kit, Enzo Life Sciences, Plymouth Meeting, PA; SAM510™: SAM Methyltransferase Assay, G-Biosciences, Saint Louis, MO; see also Zhao et al., Plant Physiol. Biochem. 48:219, 2010; Kollner et al., Plant Physiol. 153: 1195, 2010). As used herein, "activity" of an MT of the present disclosure will show detectable methylation activity on one or more target herbicides in any one of the AdoMet assays noted herein (preferably the Zhao et al. or Kollner et al. assay), whereas "minimal or no carboxyl methyltransferase activity" refers to activity that is not detectable in any one of the AdoMet assays noted herein (preferably the Zhao et al. or Kollner et al. assay) or simply is the absence of activity.

Any auxin-like herbicide may be employed in a SAM-methyltrasnferase assay, including any of the herbicides listed in Table A.

Table A. Exemplary Auxin-Like Herbicides

If an MT protein that has an increased methylation activity on a selected herbicide is identified in the assay, the MT polypeptide may be further modified to increase the activity for that herbicide or increase the specificity of that MT polypeptide for that herbicide over a natural plant compound (e.g. , salicylic acid) or both. In such embodiments, new variants made from a parental MT variant may be counter-screened against other herbicides to identify variants that have increased specificity for a selected herbicide, increased methylation activity for a selected herbicide, decreased specificity for a selected plant compound, or all three features. In these embodiments, a screening method may be used, wherein the method comprises (a) selecting a first MT protein from the library, wherein the first MT protein is able to methylate a selected herbicide; (b) subjecting the polynucleotide encoding the first MT protein to mutagenesis to produce a second library of variant MT proteins; (c) individually contacting the selected herbicide with each MT protein of the second library, in the presence of S-adenosyl-L- methionine (SAM); and (d) assaying the variant MT proteins from the second library for (i) an increased methylation activity of an MT polypeptide on a selected herbicide relative to the first MT protein; (ii) an increased specificity for the selected herbicide; (iii) a decreased specificity for a selected plant compound relative to the first MT protein; (iv) a decreased methylation activity on a selected plant compound; or (v) any combination thereof.

In some embodiments, particularly embodiments in which a library contains multiple substitutions that are distributed throughout the library such that all the members of the library each contain multiple substitutions and each substitution is present in several members of the library, the first library or the second library may be tested against a number of different herbicides or other targets affected by

methyltransferase activity, thereby allowing evaluation of the contribution of individual amino acid substitutions to either the methylation activity or the specificity of a MT polypeptide to a selected herbicide, natural plant compound, or other target of interest. The substitutions that modify the activity or selectivity of a particular MT polypeptide in a desirable way can be retained for subsequent rounds of mutagenesis and screening.

Herbicide Resistance Conferring MTs

Provided are non-naturally occurring or recombinant carboxy methyltransferase

(MT) polypeptides, wherein MT polypeptides comprising one or more amino acid substitutions at a position corresponding to those shown in Table 1 , wherein relative to a reference or parental wild-type MT protein, an altered MT protein of this disclosure has increased activity in methylating one or more selected herbicides. In certain other embodiments, an altered MT protein of this disclosure has increased activity in methylating one or more selected auxin-like herbicides (e.g., dicamba, 2,4-D) and less activity on certain natural plant hormones (e.g., salicylic acid, benzoic acid). In particular embodiments, a MT polypeptide may have at least five-fold (e.g., at least tenfold, at least twenty-fold, at least thirty-fold, at least forty-fold, at least fifty- fold, at least 75-fold, at least 100-fold or at least at least 1 ,000-fold or more) activity in methylating a selected herbicide than a reference or wild-type MT protein. In particular embodiments, a MT protein confers resistance to a plant against one, two, three, four or five herbicides (e.g., resistance may be against the two herbicides of dicamba and

2,4-D).

In certain embodiments, an MT polypeptide comprises an amino acid sequence that is at least 70% identical (e.g., at least 75% identical, at least 80% identical, at least 85% identical, at least 90% identical, at least 91% identical, at least 92% identical, at least 93% identical, at least 94% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical or at least 99% identical) to a reference or wild-type MT polypeptide and is capable of methylating at least one, two, three, four or five auxin-like herbicides, or is capable of methylating dicamba and 2,4-D, or is capable of methylating dicamba and 2,4-D and minimally or does not methylate salicylic acid.

The term "carboxy methyltransferase" (or "MT" for short) refers to an enzyme that catalyzes the methylation of a carboxyl group or nitrogen containing moiety on a substrate using co-substrate S-adenosyl-L-methionine (SAM) as a methyl donor, e.g., methylation of salicylic acid to methylsalicylic acid. A MT of the present disclosure may be any MT belonging to the SABATH (Salicylic Acid Benzoic Acid Theobromine) family of proteins. The SABATH family of proteins is described in, e.g., D'Auria et al. (Recent Advances in Phytochemistry 37:253, 2003); Zhao et al. {Tree Physiol. 29:947, 2009); Kollner et al. (Plant Physiol. 153: 1195, 2010), and other references. Other representative SABATH family members include salicylic acid methyltransferase (SAMT), benzoic acid methyltransferase (BAMT), indole-3 -acetic acid

methyltransferase (IAMT), gibberilic acid methyltransferase (GAMT), jasmonic acid methyltransferase (JMT), farnesoic acid methyltransferase (FAMT), anthranilic acid methyltransferase (AAMT), and cinnamate/p-coumarate carboxyl methyltransferase (CCMT). Some MTs recognize more than one substrate, which are then referred to as dual substrate MTs. For example, if the MT has activity on jasmonic acid and benzoic acid, or has activity on one benzoic acid and salicylic acid, then these MTs will be referred to as a JBMT and BSMT, respectively. An exemplary reference MT polypeptide sequence of the present disclosure is provided in SEQ ID NO:70. A second exemplary reference MT polypeptide sequence of the present disclosure is provided in SEQ ID NO: 83 (which can be encoded by a nucleic acid molecule as set forth in SEQ ID NO:84). In addition to carboxyl methyltransferase, the SABATH family includes a number of nitrogen directed MTs involved in caffeine biosynthesis, including xanthosine methyltransferase, theobromine methyltransferase, and caffeine

methyltransferase .

The reference or parental wild-type MT protein may be any MT protein that is a SABATH family member from any plant. Members of this newly discovered and recently characterized methyltransferase family catalyze the formation of small molecule methyl esters or N-methylated compounds using S-adenosyl-L-methionine (SAM) as a methyl donor and carboxylic acid-bearing substrate or nitrogen-containing moiety of a substrate, respectively, as methyl acceptors (D'Auria et al., Recent

Advances in Phytochemistry 37:253, 2003; Ogawa et al., J. Biol. Chem. 176:8213, 2001). Carboxylate-containing small molecules are a class of compounds that plants produce to defend against herbivory (Van Poecke et al., J. Chem. Ecol. 27:1911, 2001; Winz and Baldwin, Plant Physiol. 725:2189, 2001), to regulate the cell cycle (Staswick et al, Proc. Nat'l. Acad. Sci. USA S :6837, 1992; Smirnoff and Wheeler, Crit. Rev. Biochem. Mol. Biol. 55:291, 2000), and to induce defense responses to pathogen attack (Ryals et al, Proc. Nat'l. Acad. Sci. USA 92:4202, 1995; Feys and Parker, Trends Genet. 16:449, 2000; Nurnberger and Scheel, Trends Plant Sci. 6:372, 2001).

Such compounds can be esterified and volatilized to serve, for example, as attractants for pollinators and seed dispersers (Dobson and Bergstrom, Plant Syst. Evol. 222:63, 2000; Knudsen et al., Bot. Rev. 72: 1, 2006) and for other types of plant-insect and plant-plant communications (Shulaev et al., Nature 355:718, 1997; Kessler and Baldwin, Science 291:2141, 2001; Howe and Jander, Annu. Rev. Plant Biol. 59:41, 2008). For example, the genome of Arabidopsis thaliana contains 24 MT genes (Yang et al., Arch. Biochem. Biophys. 448: 123, 2006) and the genome of Oryza sativa contains 41 MT genes {see Zhao et al., Plant Physiol. 146:455, 2008). In certain embodiments, the reference SABATH MT nucleic acid molecule sequence is from Oryza sativa subspecies Indica (e.g., SEQ ID NO:22), Oryza sativa subspecies Japonica (e.g., SEQ ID NO: 84), or Oryza sativa subspecies Javanica.

The design of MT variants and nucleic acids encoding the same may be done using the phylogenetic-based methods described in, for example, U.S. Patent No.

8,005,620 and Gustafsson (Curr. Opin. Biotechnol. 14:366, 2003; which are

incorporated by reference for disclosure of such methods) as well as Welch et al. (J. R. Soc. Interface. 6: S467, 2009), Villalobos et al. (BMC Bioinformatics 7: 285, 2006) Minshull et al. (Curr. Opin. Chem. Biol. 9:202, 2005), Gustafsson et al. (Trends Biotechnol. 22:346, 2004) and Minshull (Methods 32:416, 2004). The amino acid substitutions may be determined by a phylogenetic analysis of related MT sequences.

In certain embodiments, the identity and position of the amino acid being substituted may be selected from Table 2, e.g., from the fields that are in bold and underlined in Table 2, or combinations thereof. In particular cases, an amino acid substitution may be independently selected from Table 2 or conservative amino acid substitutions of the amino acid substitutions shown in Table 2, or combinations thereof.

In some embodiments, an MT polypeptide may comprise at least two amino acid substitutions at residues corresponding to the pairwise combinations of

substitutable positions shown in Table 3. In certain embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 pairs of pre-identified mutation sites from Table 3 are combined in one nucleic acid molecule encoding a MT polypeptide of the instant disclosure. Table 3. Pairwise Combinations of Substitutable Positions

Positions Positions Positions Positions Positions

437/550 572/ 184 183 /399 436/239 431 /568

437/368 572/401 183 /434 436/487 431 /373

437/372 572/584 183 /581 436/550 431 /330

437/430 572/239 183/448 436/368 431 /404

437/238 572/487 183 /403 436/372 431 / 181

437/ 186 572/550 183 /281 436/430 431 /357

437/230 572/368 183 /594 436/238 431 /299

437/543 572 / 372 183 /553 436/ 186 431 /399

437/472 572/430 183 /580 436/230 431 /434

437/464 572/238 183 /305 436/543 431 /581

437/546 572/ 186 183/98 436/472 431 /448

437/300 572/230 183 /496 436/464 431 /403

437/549 572 / 543 183 /532 436/546 431 /281

437/ 154 572 / 472 183 /462 436/300 431 /594

437/453 572 / 464 183/189 436/549 431 /553

437/467 572 / 546 183/440 436/ 154 431 /580

437/530 572/300 183 /608 436/453 431 /305

437/547 572 / 549 183/140 436/467 431/98

437/348 572/ 154 183/223 436/530 431 /496

437/568 572/453 183/213 436/547 431 /532

437/373 572 / 467 183/222 436/348 431 /462

437/330 572/530 183/77 436/568 431 / 189

437/404 572 / 547 183/220 436/373 431 /440

437/ 181 572/348 183/429 436/330 431 /608

437/357 572/568 183/447 436/404 431 / 140

437/299 572/373 183/194 436/ 181 431 /223

437/399 572/330 183 /285 436/357 431/213

437/434 572 / 404 183/426 436/299 431 /222

437/581 572/ 181 183/144 436/399 431/77

437/448 572/357 183 /387 436/434 431 /220

437/403 572 / 299 183/428 436/581 431 /429

437/281 572/399 183 /296 436/448 431 /447

437/594 572/434 183/224 436/403 431 / 194

437/553 572/581 183 /298 436/281 431 /285

437/580 572 / 448 183 /600 436/594 431 /426

437/305 572 / 403 183 /475 436/553 431 / 144

437/98 572/281 183 /287 436/580 431 /387

437/496 572 / 594 183/115 436/305 431 /428

437/532 572/553 183 /331 436/98 431 /296

437/462 572/580 183 /409 436/496 431 /224

437/ 189 572/305 183 /541 436/532 431 /298 Positions Positions Positions Positions Positions

437/440 572 / 98 183/411 436/462 431 /600

437/608 572 / 496 183/217 436/ 189 431 /475

437/ 140 572/532 183/228 436/440 431 /287

437/223 572 / 462 183/188 436/608 431 / 115

437/213 572/ 189 183 /579 436/ 140 431 /331

437 / 222 572 / 440 183/153 436/223 431 /409

437/77 572 / 608 183/76 436/213 431 /541

437/220 572/ 140 236/365 436 / 222 431/411

437/429 572 / 223 236/537 436/77 431/217

437/447 572/213 236/433 436/220 431 /228

437/ 194 572 / 222 236/477 436/429 431 / 188

437/285 572 / 77 236/555 436/447 431 /579

437/426 572 / 220 236/436 436/ 194 431 / 153

437/ 144 572 / 429 236/479 436/285 431/76

437/387 572 / 447 236/578 436/426 390/221

437/428 572/ 194 236/277 436/ 144 390/596

437/296 572/285 236/483 436/387 390/533

437 / 224 572 / 426 236/ 145 436/428 390/282

437/298 572 / 144 236/276 436/296 390/400

437/600 572/387 236/431 436 / 224 390/435

437/475 572 / 428 236/390 436/298 390/308

437/287 572 / 296 236/221 436/600 390/490

437/ 115 572 / 224 236/596 436/475 390/ 184

437/331 572/298 236/533 436/287 390/401

437/409 572 / 600 236/282 436/ 115 390/584

437/541 572 / 475 236/400 436/331 390/239

437/411 572/287 236/435 436/409 390/487

437/217 572/ 115 236/308 436/541 390/550

437/228 572/331 236/490 436/411 390/368

437/ 188 572 / 409 236/ 184 436/217 390/372

437/579 572/541 236/401 436/228 390/430

437/ 153 572/411 236/584 436/ 188 390/238

437/76 572/217 236/239 436/579 390/ 186

414/307 572 / 228 236/487 436/ 153 390/230

414/274 572/ 188 236/550 436/76 390/543

414/358 572 / 579 236/368 479/578 390/472

414/242 572/ 153 236/372 479 / 277 390/464

414/572 572 / 76 236/430 479/483 390/546

414/326 326/397 236/238 479/ 145 390/300

414/397 326 / 226 236/ 186 479 / 276 390/549

414/226 326/575 236/230 479/431 390/ 154 Positions Positions Positions Positions Positions

414/575 326/385 236/543 479/390 390/453

414/385 326/ 183 236/472 479/221 390/467

414/183 326/236 236/464 479 / 596 390/530

414/236 326/365 236/546 479/533 390/547

414/365 326/537 236/300 479/282 390/348

414/537 326/433 236/549 479 / 400 390/568

414/433 326/477 236/ 154 479/435 390/373

414/477 326/555 236/453 479/308 390/330

414/555 326/436 236/467 479 / 490 390/404

414/436 326/479 236/530 479/ 184 390/ 181

414/479 326/578 236/547 479/401 390/357

414/578 326/277 236/348 479/584 390/299

414/277 326/483 236/568 479/239 390/399

414/483 326/ 145 236/373 479/487 390/434

414/145 326/276 236/330 479/550 390/581

414/276 326/431 236/404 479/368 390/448

414/431 326/390 236/ 181 479 / 372 390/403

414/390 326/221 236/357 479/430 390/281

414/221 326/596 236/299 479/238 390/594

414/596 326/533 236/399 479/ 186 390/553

414/533 326/282 236/434 479/230 390/580

414/282 326/400 236/581 479 / 543 390/305

414/400 326/435 236/448 479 / 472 390/98

414/435 326/308 236/403 479 / 464 390/496

414/308 326/490 236/281 479 / 546 390/532

414/490 326/ 184 236/594 479/300 390/462

414/184 326/401 236/553 479 / 549 390/ 189

414/401 326/584 236/580 479/ 154 390/440

414/584 326/239 236/305 479/453 390/608

414/239 326/487 236/98 479 / 467 390/ 140

414/487 326/550 236/496 479/530 390/223

414/550 326/368 236/532 479 / 547 390/213

414/368 326/372 236/462 479/348 390 / 222

414/372 326/430 236/ 189 479/568 390/77

414/430 326/238 236/440 479/373 390/220

414/238 326/ 186 236/608 479/330 390/429

414/186 326/230 236/ 140 479 / 404 390/447

414/230 326 / 543 236/223 479/ 181 390/ 194

414/543 326 / 472 236/213 479/357 390/285

414/472 326 / 464 236 / 222 479 / 299 390/426

414/464 326 / 546 236/77 479/399 390/ 144 Positions Positions Positions Positions Positions

414/546 326/300 236/220 479/434 390/387

414/300 326 / 549 236/429 479/581 390/428

414/549 326/ 154 236/447 479 / 448 390/296

414/154 326/453 236/ 194 479 / 403 390 / 224

414/453 326/467 236/285 479/281 390/298

414/467 326/530 236/426 479 / 594 390/600

414/530 326 / 547 236/ 144 479/553 390/475

414/547 326/348 236/387 479/580 390/287

414/348 326/568 236/428 479/305 390/ 115

414/568 326/373 236/296 479 / 98 390/331

414/373 326/330 236 / 224 479 / 496 390/409

414/330 326 / 404 236/298 479/532 390/541

414/404 326/ 181 236/600 479 / 462 390/411

414/181 326/357 236/475 479/ 189 390/217

414/357 326/299 236/287 479 / 440 390/228

414/299 326/399 236/ 115 479 / 608 390/ 188

414/399 326/434 236/331 479/ 140 390/579

414/434 326/581 236/409 479 / 223 390/ 153

414/581 326/448 236/541 479/213 390/76

414/448 326/403 236/411 479 / 222 221 /596

414/403 326/281 236/217 479 / 77 221 /533

414/281 326 / 594 236/228 479 / 220 221 /282

414/594 326/553 236/ 188 479 / 429 221 /400

414/553 326/580 236/579 479 / 447 221 /435

414/580 326/305 236/ 153 479/ 194 221 /308

414/305 326/98 236/76 479/285 221 /490

414/98 326/496 365/537 479 / 426 221 / 184

414/496 326/532 365/433 479 / 144 221 /401

414/532 326 / 462 365/477 479/387 221 /584

414/462 326/ 189 365/555 479 / 428 221 /239

414/189 326 / 440 365/436 479 / 296 221 /487

414/440 326/608 365/479 479 / 224 221 /550

414/608 326/ 140 365/578 479/298 221 /368

414/140 326 / 223 365/277 479 / 600 221 /372

414/223 326/213 365/483 479 / 475 221 /430

414/213 326 / 222 365/ 145 479/287 221 /238

414/222 326 / 77 365/276 479/ 115 221 / 186

414/77 326 / 220 365/431 479/331 221 /230

414/220 326 / 429 365/390 479 / 409 221 /543

414/429 326 / 447 365/221 479/541 221 /472

414/447 326/ 194 365/596 479/411 221 /464 Positions Positions Positions Positions Positions

414/194 326/285 365/533 479/217 221 /546

414/285 326 / 426 365/282 479 / 228 221 /300

414/426 326/ 144 365/400 479/ 188 221 /549

414/144 326/387 365/435 479 / 579 221 / 154

414/387 326/428 365/308 479/ 153 221 /453

414/428 326/296 365/490 479 / 76 221 /467

414/296 326 / 224 365/ 184 578/277 221 /530

414/224 326/298 365/401 578 /483 221 /547

414/298 326 / 600 365/584 578/ 145 221 /348

414/600 326/475 365/239 578/276 221 /568

414/475 326/287 365/487 578 /431 221 /373

414/287 326/ 115 365/550 578 /390 221 /330

414/115 326/331 365/368 578/221 221 /404

414/331 326/409 365/372 578 /596 221 / 181

414/409 326/541 365/430 578 /533 221 /357

414/541 326/411 365/238 578 /282 221 /299

414/411 326/217 365/ 186 578/400 221 /399

414/217 326/228 365/230 578 /435 221 /434

414/228 326/ 188 365/543 578 /308 221 /581

414/188 326/579 365/472 578/490 221 /448

414/579 326/ 153 365/464 578 / 184 221 /403

414/153 326 / 76 365/546 578/401 221 /281

414/76 397/226 365/300 578 /584 221 /594

307/274 397/575 365/549 578 /239 221 /553

307/358 397/385 365/ 154 578 /487 221 /580

307 / 242 397/ 183 365/453 578 /550 221 /305

307/572 397/236 365/467 578 /368 221/98

307/326 397/365 365/530 578 /372 221 /496

307/397 397/537 365/547 578 /430 221 /532

307/226 397/433 365/348 578 /238 221 /462

307/575 397/477 365/568 578 / 186 221 / 189

307/385 397/555 365/373 578 /230 221 /440

307/ 183 397/436 365/330 578 /543 221 /608

307/236 397/479 365/404 578/472 221 / 140

307/365 397/578 365/ 181 578/464 221 /223

307/537 397/277 365/357 578 /546 221/213

307/433 397/483 365/299 578 /300 221 /222

307/477 397/ 145 365/399 578 /549 221/77

307/555 397/276 365/434 578 / 154 221 /220

307/436 397/431 365/581 578 /453 221 /429

307/479 397/390 365/448 578/467 221 /447 Positions Positions Positions Positions Positions

307/578 397/221 365/403 578 /530 221 / 194

307/277 397/596 365/281 578 /547 221 /285

307/483 397/533 365/594 578 /348 221 /426

307/ 145 397/282 365/553 578 /568 221 / 144

307/276 397/400 365/580 578 /373 221 /387

307/431 397/435 365/305 578 /330 221 /428

307/390 397/308 365 /98 578/404 221 /296

307/221 397/490 365/496 578 / 181 221 /224

307/596 397/ 184 365/532 578 /357 221 /298

307/533 397/401 365/462 578/299 221 /600

307/282 397/584 365/ 189 578 /399 221 /475

307/400 397/239 365/440 578 /434 221 /287

307/435 397/487 365/608 578 /581 221 / 115

307/308 397/550 365/ 140 578/448 221 /331

307/490 397/368 365/223 578/403 221 /409

307/ 184 397/372 365/213 578 /281 221 /541

307/401 397/430 365 / 222 578 /594 221/411

307/584 397/238 365 /77 578 /553 221/217

307/239 397/ 186 365/220 578 /580 221 /228

307/487 397/230 365/429 578 /305 221 / 188

307/550 397/543 365/447 578/98 221 /579

307/368 397/472 365/ 194 578/496 221 / 153

307/372 397/464 365/285 578 /532 221/76

307/430 397/546 365/426 578/462 596/533

307/238 397/300 365/ 144 578 / 189 596/282

307/ 186 397/549 365/387 578/440 596/400

307/230 397/ 154 365/428 578 /608 596/435

307/543 397/453 365/296 578/ 140 596/308

307/472 397/467 365 / 224 578/223 596/490

307/464 397/530 365/298 578/213 596/ 184

307/546 397/547 365/600 578 / 222 596/401

307/300 397/348 365/475 578/77 596/584

307/549 397/568 365/287 578/220 596/239

307/ 154 397/373 365/ 115 578/429 596/487

307/453 397/330 365/331 578/447 596/550

307/467 397/404 365/409 578 / 194 596/368

307/530 397/ 181 365/541 578 /285 596/372

307/547 397/357 365/411 578/426 596/430

307/348 397/299 365/217 578 / 144 596/238

307/568 397/399 365/228 578 /387 596/ 186

307/373 397/434 365/ 188 578/428 596/230 Positions Positions Positions Positions Positions

307/330 397/581 365/579 578/296 596 / 543

307/404 397/448 365/ 153 578 / 224 596 / 472

307/ 181 397/403 365 /76 578/298 596 / 464

307/357 397/281 537/433 578 /600 596 / 546

307/299 397/594 537/477 578/475 596/300

307/399 397/553 537/555 578 /287 596 / 549

307/434 397/580 537/436 578 / 115 596/ 154

307/581 397/305 537/479 578 /331 596/453

307/448 397/98 537/578 578/409 596/467

307/403 397/496 537/277 578 /541 596/530

307/281 397/532 537/483 578/411 596 / 547

307/594 397/462 537/ 145 578/217 596/348

307/553 397/ 189 537/276 578/228 596/568

307/580 397/440 537/431 578 / 188 596/373

307/305 397/608 537/390 578 /579 596/330

307/98 397/ 140 537/221 578 / 153 596 / 404

307/496 397/223 537/596 578/76 596/ 181

307/532 397/213 537/533 277/483 596/357

307/462 397 / 222 537/282 277/ 145 596/299

307/ 189 397/77 537/400 277 / 276 596/399

307/440 397/220 537/435 277/431 596/434

307/608 397/429 537/308 277/390 596/581

307/ 140 397/447 537/490 277/221 596/448

307/223 397/ 194 537/ 184 277 / 596 596/403

307/213 397/285 537/401 277/533 596/281

307 / 222 397/426 537/584 277/282 596 / 594

307/77 397/ 144 537/239 277 / 400 596/553

307/220 397/387 537/487 277/435 596/580

307/429 397/428 537/550 277/308 596/305

307/447 397/296 537/368 277 / 490 596/98

307/ 194 397 / 224 537/372 277/ 184 596/496

307/285 397/298 537/430 277/401 596/532

307/426 397/600 537/238 277/584 596 / 462

307/ 144 397/475 537/ 186 277/239 596/ 189

307/387 397/287 537/230 277/487 596 / 440

307/428 397/ 115 537/543 277/550 596/608

307/296 397/331 537/472 277/368 596/ 140

307 / 224 397/409 537/464 277 / 372 596 / 223

307/298 397/541 537/546 277/430 596/213

307/600 397/411 537/300 277/238 596 / 222

307/475 397/217 537/549 277/ 186 596 / 77 Positions Positions Positions Positions Positions

307/287 397/228 537/ 154 277/230 596 / 220

307/ 115 397/ 188 537/453 277 / 543 596 / 429

307/331 397/579 537/467 277 / 472 596 / 447

307/409 397/ 153 537/530 277 / 464 596/ 194

307/541 397/76 537/547 277 / 546 596/285

307/411 226 / 575 537/348 277/300 596 / 426

307/217 226/385 537/568 277 / 549 596/ 144

307/228 226/ 183 537/373 277/ 154 596/387

307/ 188 226/236 537/330 277/453 596/428

307/579 226 / 365 537/404 277 / 467 596/296

307/ 153 226/537 537/ 181 277/530 596 / 224

307/76 226/433 537/357 277 / 547 596/298

274/358 226 / 477 537/299 277/348 596 / 600

274 / 242 226 / 555 537/399 277/568 596/475

274 / 572 226/436 537/434 277/373 596/287

274 / 326 226 / 479 537/581 277/330 596/ 115

274 / 397 226 / 578 537/448 277 / 404 596/331

274 / 226 226 / 277 537/403 277/ 181 596/409

274 / 575 226/483 537/281 277/357 596/541

274/385 226 / 145 537/594 277 / 299 596/411

274/ 183 226 / 276 537/553 277/399 596/217

274/236 226/431 537/580 277/434 596/228

274 / 365 226 / 390 537/305 277/581 596/ 188

274/537 226/221 537/98 277 / 448 596/579

274/433 226 / 596 537/496 277 / 403 596/ 153

274 / 477 226/533 537/532 277/281 596 / 76

274 / 555 226 / 282 537/462 277 / 594 533 /282

274/436 226 / 400 537/ 189 277/553 533 /400

274 / 479 226/435 537/440 277/580 533 /435

274 / 578 226/308 537/608 277/305 533 /308

274 / 277 226 / 490 537/ 140 277 / 98 533 /490

274/483 226/ 184 537/223 277 / 496 533 / 184

274/ 145 226/401 537/213 277/532 533 /401

274 / 276 226 / 584 537/222 277 / 462 533 /584

274/431 226/239 537/77 277/ 189 533 /239

274 / 390 226/487 537/220 277 / 440 533 /487

274/221 226 / 550 537/429 277 / 608 533 /550

274 / 596 226/368 537/447 277/ 140 533 /368

274/533 226 / 372 537/ 194 277 / 223 533 /372

274 / 282 226/430 537/285 277/213 533 /430

274 / 400 226/238 537/426 277 / 222 533 /238 Positions Positions Positions Positions Positions

274/435 226/ 186 537/ 144 277 / 77 533 / 186

274/308 226/230 537/387 277 / 220 533 /230

274 / 490 226 / 543 537/428 277 / 429 533 /543

274/ 184 226 / 472 537/296 277 / 447 533 /472

274/401 226 / 464 537/224 277/ 194 533 /464

274 / 584 226 / 546 537/298 277/285 533 /546

274/239 226 / 300 537/600 277 / 426 533 /300

274/487 226 / 549 537/475 277 / 144 533 /549

274 / 550 226/ 154 537/287 277/387 533 / 154

274/368 226 / 453 537/ 115 277 / 428 533 /453

274 / 372 226 / 467 537/331 277 / 296 533 /467

274/430 226/530 537/409 277 / 224 533 /530

274/238 226 / 547 537/541 277/298 533 /547

274/ 186 226 / 348 537/411 277 / 600 533 /348

274/230 226 / 568 537/217 277 / 475 533 /568

274 / 543 226 / 373 537/228 277/287 533 /373

274 / 472 226/330 537/ 188 277/ 115 533 /330

274 / 464 226 / 404 537/579 277/331 533 /404

274 / 546 226/ 181 537/ 153 277 / 409 533 / 181

274 / 300 226/357 537/76 277/541 533 /357

274 / 549 226 / 299 433/477 277/411 533 /299

274/ 154 226 / 399 433 /555 277/217 533 /399

274 / 453 226 / 434 433 /436 277 / 228 533 /434

274 / 467 226/581 433/479 277/ 188 533 /581

274/530 226 / 448 433 /578 277 / 579 533 /448

274 / 547 226 / 403 433/277 277/ 153 533 /403

274 / 348 226/281 433 /483 277 / 76 533 /281

274 / 568 226 / 594 433/ 145 483 / 145 533 /594

274 / 373 226 / 553 433/276 483 /276 533 /553

274/330 226/580 433 /431 483 /431 533 /580

274 / 404 226 / 305 433 /390 483 /390 533 /305

274/ 181 226 / 98 433/221 483 /221 533 /98

274/357 226 / 496 433 /596 483 /596 533 /496

274 / 299 226 / 532 433 /533 483 /533 533 /532

274 / 399 226 / 462 433 /282 483 /282 533 /462

274 / 434 226/ 189 433/400 483 /400 533 / 189

274/581 226 / 440 433 /435 483 /435 533 /440

274 / 448 226 / 608 433 /308 483 /308 533 /608

274 / 403 226 / 140 433/490 483 /490 533 / 140

274/281 226 / 223 433 / 184 483 / 184 533 /223

274 / 594 226/213 433/401 483 /401 533 /213 Positions Positions Positions Positions Positions

274 / 553 226 / 222 433 /584 483 /584 533 /222

274/580 226 / 77 433 /239 483 /239 533 /77

274 / 305 226 / 220 433 /487 483 /487 533 /220

274 / 98 226 / 429 433 /550 483 /550 533 /429

274 / 496 226 / 447 433 /368 483 /368 533 /447

274 / 532 226/ 194 433 /372 483 /372 533 / 194

274 / 462 226/285 433 /430 483 /430 533 /285

274/ 189 226 / 426 433 /238 483 /238 533 /426

274 / 440 226 / 144 433 / 186 483 / 186 533 / 144

274 / 608 226/387 433 /230 483 /230 533 /387

274/ 140 226 / 428 433 /543 483 /543 533 /428

274 / 223 226 / 296 433/472 483 /472 533 /296

274/213 226 / 224 433/464 483 /464 533 /224

274 / 222 226 / 298 433 /546 483 /546 533 /298

274 / 77 226 / 600 433 /300 483 /300 533 /600

274 / 220 226 / 475 433 /549 483 /549 533 /475

274 / 429 226/287 433 / 154 483 / 154 533 /287

274 / 447 226/ 115 433 /453 483 /453 533 / 115

274/ 194 226/331 433/467 483 /467 533 /331

274/285 226 / 409 433 /530 483 /530 533 /409

274 / 426 226/541 433 /547 483 /547 533 /541

274/ 144 226/411 433 /348 483 /348 533 /411

274/387 226/217 433 /568 483 /568 533 /217

274 / 428 226 / 228 433 /373 483 /373 533 /228

274 / 296 226/ 188 433 /330 483 /330 533 / 188

274 / 224 226 / 579 433/404 483 /404 533 /579

274 / 298 226/ 153 433 / 181 483 / 181 533 / 153

274 / 600 226 / 76 433 /357 483 /357 533 /76

274 / 475 575 /385 433/299 483 /299 282/400

274/287 575 / 183 433 /399 483 /399 282/435

274/ 115 575 /236 433 /434 483 /434 282/308

274/331 575 /365 433 /581 483 /581 282/490

274 / 409 575 /537 433/448 483 /448 282/ 184

274/541 575 /433 433/403 483 /403 282/401

274/411 575/477 433 /281 483 /281 282/584

274/217 575 /555 433 /594 483 /594 282/239

274 / 228 575 /436 433 /553 483 /553 282/487

274/ 188 575/479 433 /580 483 /580 282/550

274 / 579 575 /578 433 /305 483 /305 282/368

274/ 153 575/277 433 /98 483 /98 282/372

274 / 76 575 /483 433/496 483 /496 282/430 Positions Positions Positions Positions Positions

358/242 575 / 145 433 /532 483 /532 282/238

358/572 575/276 433/462 483 /462 282/ 186

358/326 575 /431 433 / 189 483 / 189 282/230

358/397 575 /390 433/440 483 /440 282 / 543

358/226 575/221 433 /608 483 /608 282 / 472

358/575 575 /596 433/ 140 483 / 140 282 / 464

358 /385 575 /533 433/223 483 /223 282 / 546

358 / 183 575 /282 433/213 483 /213 282/300

358/236 575/400 433 / 222 483 / 222 282 / 549

358/365 575 /435 433 /77 483 /77 282/ 154

358 /537 575 /308 433/220 483 /220 282/453

358/433 575/490 433/429 483 /429 282/467

358/477 575 / 184 433/447 483 /447 282/530

358/555 575/401 433 / 194 483 / 194 282 / 547

358/436 575 /584 433 /285 483 /285 282/348

358/479 575 /239 433/426 483 /426 282/568

358/578 575 /487 433 / 144 483 / 144 282/373

358/277 575 /550 433 /387 483 /387 282/330

358/483 575 /368 433/428 483 /428 282 / 404

358/ 145 575 /372 433/296 483 /296 282/ 181

358/276 575 /430 433 / 224 483 / 224 282/357

358/431 575 /238 433/298 483 /298 282/299

358/390 575 / 186 433 /600 483 /600 282/399

358/221 575 /230 433/475 483 /475 282/434

358/596 575 / 543 433 /287 483 /287 282/581

358 /533 575 / 472 433 / 115 483 / 115 282/448

358/282 575 / 464 433 /331 483 /331 282/403

358/400 575 / 546 433/409 483 /409 282/281

358/435 575 /300 433 /541 483 /541 282 / 594

358/308 575 / 549 433/411 483 /411 282/553

358/490 575 / 154 433/217 483 /217 282/580

358 / 184 575/453 433/228 483 /228 282/305

358/401 575/467 433 / 188 483 / 188 282/98

358 /584 575 /530 433 /579 483 /579 282/496

358/239 575 / 547 433 / 153 483 / 153 282/532

358/487 575 /348 433 /76 483 /76 282 / 462

358/550 575 /568 477/555 145/276 282/ 189

358/368 575 /373 477/436 145/431 282 / 440

358/372 575 /330 477 / 479 145/390 282/608

358/430 575 / 404 477/578 145/221 282/ 140

358/238 575 / 181 477 / 277 145/596 282 / 223 Positions Positions Positions Positions Positions

358 / 186 575 /357 477/483 145 /533 282/213

358/230 575/299 477/ 145 145/282 282 / 222

358/543 575 /399 477 / 276 145/400 282 / 77

358/472 575 /434 477/431 145/435 282 / 220

358/464 575 /581 477/390 145/308 282 / 429

358/546 575/448 477/221 145/490 282 / 447

358/300 575/403 477 / 596 145/184 282/ 194

358/549 575 /281 477/533 145/401 282/285

358/ 154 575 / 594 477/282 145 /584 282 / 426

358/453 575 /553 477 / 400 145/239 282/ 144

358/467 575 /580 477/435 145/487 282/387

358 /530 575 /305 477/308 145/550 282/428

358/547 575/98 477 / 490 145/368 282/296

358/348 575/496 477/ 184 145/372 282 / 224

358/568 575 /532 477/401 145/430 282/298

358/373 575 / 462 477/584 145/238 282 / 600

358 /330 575 / 189 477/239 145/186 282/475

358/404 575 / 440 477/487 145/230 282/287

358 / 181 575/608 477/550 145/543 282/ 115

358 /357 575 / 140 477/368 145/472 282/331

358/299 575 / 223 477 / 372 145/464 282/409

358/399 575/213 477/430 145/546 282/541

358/434 575 / 222 477/238 145/300 282/411

358 /581 575 / 77 477/ 186 145/549 282/217

358/448 575 / 220 477/230 145/154 282/228

358/403 575 / 429 477 / 543 145/453 282/ 188

358/281 575 / 447 477 / 472 145/467 282/579

358/594 575/ 194 477 / 464 145 /530 282/ 153

358/553 575 /285 477 / 546 145/547 282 / 76

358 /580 575 / 426 477/300 145/348 400/435

358/305 575 / 144 477 / 549 145/568 400/308

358 /98 575 /387 477/ 154 145/373 400 / 490

358/496 575/428 477/453 145 /330 400/ 184

358 /532 575/296 477 / 467 145/404 400/401

358/462 575 / 224 477/530 145/181 400/584

358 / 189 575/298 477 / 547 145 /357 400/239

358/440 575 / 600 477/348 145/299 400/487

358/608 575/475 477/568 145/399 400/550

358/ 140 575 /287 477/373 145/434 400/368

358/223 575 / 115 477/330 145 /581 400 / 372

358/213 575 /331 477 / 404 145/448 400/430 Positions Positions Positions Positions Positions

358/222 575/409 477/ 181 145/403 400/238

358 /77 575/541 477/357 145/281 400/ 186

358/220 575/411 477 / 299 145/594 400/230

358/429 575/217 477/399 145/553 400 / 543

358/447 575/228 477/434 145 /580 400 / 472

358/ 194 575 / 188 477/581 145/305 400 / 464

358/285 575 /579 477 / 448 145/98 400 / 546

358/426 575 / 153 477 / 403 145/496 400/300

358/ 144 575 / 76 477/281 145 /532 400 / 549

358 /387 385 / 183 477 / 594 145/462 400/ 154

358/428 385 /236 477/553 145/189 400/453

358/296 385 /365 477/580 145/440 400 / 467

358/224 385 /537 477/305 145/608 400/530

358/298 385 /433 477 / 98 145/140 400 / 547

358/600 385 /477 477 / 496 145/223 400/348

358/475 385 /555 477/532 145/213 400/568

358/287 385 /436 477 / 462 145/222 400/373

358 / 115 385 /479 477/ 189 145/77 400/330

358 /331 385 /578 477 / 440 145/220 400 / 404

358/409 385 /277 477 / 608 145/429 400/ 181

358/541 385 /483 477/ 140 145/447 400/357

358/411 385 / 145 477 / 223 145/194 400 / 299

358/217 385 /276 477/213 145/285 400/399

358/228 385 /431 477 / 222 145/426 400/434

358 / 188 385 /390 477 / 77 145/144 400/581

358/579 385 /221 477 / 220 145 /387 400 / 448

358/ 153 385 /596 477 / 429 145/428 400 / 403

358 /76 385 /533 477 / 447 145/296 400/281

242 / 572 385 /282 477/ 194 145/224 400 / 594

242 / 326 385 /400 477/285 145/298 400/553

242 / 397 385 /435 477 / 426 145/600 400/580

242 / 226 385 /308 477/ 144 145/475 400/305

242 / 575 385 /490 477/387 145/287 400 / 98

242/385 385 / 184 477 / 428 145/115 400 / 496

242/ 183 385 /401 477 / 296 145 /331 400/532

242 / 236 385 /584 477 / 224 145/409 400 / 462

242 / 365 385 /239 477/298 145/541 400/ 189

242 / 537 385 /487 477 / 600 145/411 400 / 440

242 / 433 385 /550 477 / 475 145/217 400 / 608

242 / 477 385 /368 477/287 145/228 400/ 140

242 / 555 385 /372 477/ 115 145/188 400 / 223 Positions Positions Positions Positions Positions

242 / 436 385 /430 477/331 145/579 400/213

242 / 479 385 /238 477 / 409 145/153 400 / 222

242 / 578 385 / 186 477/541 145/76 400 / 77

242 / 277 385 /230 477/411 276/431 400 / 220

242 / 483 385 /543 477/217 276/390 400 / 429

242/ 145 385 /472 477 / 228 276/221 400 / 447

242 / 276 385 /464 477/ 188 276 / 596 400/ 194

242/431 385 /546 477 / 579 276/533 400/285

242 / 390 385 /300 477/ 153 276/282 400 / 426

242/221 385 /549 477 / 76 276 / 400 400/ 144

242 / 596 385 / 154 555/436 276/435 400/387

242 / 533 385 /453 555/479 276/308 400 / 428

242 / 282 385 /467 555/578 276 / 490 400 / 296

242 / 400 385 /530 555/277 276/ 184 400 / 224

242 / 435 385 /547 555/483 276/401 400/298

242 / 308 385 /348 555/ 145 276/584 400 / 600

242 / 490 385 /568 555/276 276/239 400 / 475

242/ 184 385 /373 555/431 276/487 400/287

242/401 385 /330 555/390 276/550 400/ 115

242 / 584 385 /404 555/221 276/368 400/331

242 / 239 385 / 181 555/596 276 / 372 400 / 409

242 / 487 385 /357 555/533 276/430 400/541

242 / 550 385 /299 555/282 276/238 400/411

242 / 368 385 /399 555/400 276/ 186 400/217

242 / 372 385 /434 555/435 276/230 400 / 228

242 / 430 385 /581 555/308 276 / 543 400/ 188

242/238 385 /448 555/490 276 / 472 400 / 579

242/ 186 385 /403 555/ 184 276 / 464 400/ 153

242 / 230 385 /281 555/401 276 / 546 400 / 76

242 / 543 385 /594 555/584 276/300 435/308

242 / 472 385 /553 555/239 276 / 549 435/490

242 / 464 385 /580 555/487 276/ 154 435/ 184

242 / 546 385 /305 555/550 276/453 435/401

242 / 300 385/98 555/368 276 / 467 435/584

242 / 549 385 /496 555/372 276/530 435/239

242/ 154 385 /532 555/430 276 / 547 435/487

242 / 453 385 /462 555/238 276/348 435/550

242 / 467 385 / 189 555/ 186 276/568 435/368

242 / 530 385 /440 555/230 276/373 435/372

242 / 547 385 /608 555/543 276/330 435/430

242 / 348 385 / 140 555/472 276 / 404 435/238 Positions Positions Positions Positions Positions

242 / 568 385 /223 555/464 276/ 181 435/ 186

242 / 373 385 /213 555/546 276/357 435/230

242/330 385 /222 555/300 276 / 299 435/543

242 / 404 385/77 555/549 276/399 435/472

242/ 181 385 /220 555/ 154 276/434 435/464

242 / 357 385 /429 555/453 276/581 435/546

242 / 299 385 /447 555/467 276 / 448 435/300

242 / 399 385 / 194 555/530 276 / 403 435/549

242 / 434 385 /285 555/547 276/281 435/ 154

242/581 385 /426 555/348 276 / 594 435/453

242 / 448 385 / 144 555/568 276/553 435/467

242 / 403 385 /387 555/373 276/580 435/530

242/281 385 /428 555/330 276/305 435/547

242 / 594 385 /296 555/404 276 / 98 435/348

242 / 553 385 /224 555/ 181 276 / 496 435/568

242 / 580 385 /298 555/357 276/532 435/373

242 / 305 385 /600 555/299 276 / 462 435/330

242 / 98 385 /475 555/399 276/ 189 435/404

242 / 496 385 /287 555/434 276 / 440 435/ 181

242 / 532 385 / 115 555/581 276 / 608 435/357

242 / 462 385 /331 555/448 276/ 140 435/299

242/ 189 385 /409 555/403 276 / 223 435/399

242 / 440 385 /541 555/281 276/213 435/434

242 / 608 385 /411 555/594 276 / 222 435/581

242/ 140 385 /217 555/553 276 / 77 435/448

242 / 223 385 /228 555/580 276 / 220 435/403

242/213 385 / 188 555/305 276 / 429 435/281

242 / 222 385 /579 555 /98 276 / 447 435/594

242 / 77 385 / 153 555/496 276/ 194 435/553

242 / 220 385/76 555/532 276/285 435/580

242 / 429 183 /236 555/462 276 / 426 435/305

242 / 447 183 /365 555/ 189 276 / 144 435/98

242/ 194 183 /537 555/440 276/387 435/496

242 / 285 183 /433 555/608 276 / 428 435/532

242 / 426 183 /477 555/ 140 276 / 296 435/462

242/ 144 183 /555 555/223 276 / 224 435/ 189

242/387 183 /436 555/213 276/298 435/440

242 / 428 183 /479 555 / 222 276 / 600 435/608

242 / 296 183 /578 555 /77 276 / 475 435/ 140

242 / 224 183 /277 555/220 276/287 435/223

242 / 298 183 /483 555/429 276/ 115 435/213 Positions Positions Positions Positions Positions

242 / 600 183/145 555/447 276/331 435 / 222

242 / 475 183 /276 555/ 194 276 / 409 435/77

242 / 287 183 /431 555/285 276/541 435/220

435/429 368 / 181 300/530 404 / 224 496 / 579

435/447 368 /357 300/547 404 / 298 496/ 153

435/ 194 368 /299 300/348 404 / 600 496 / 76

435/285 368 /399 300/568 404 / 475 532/462

435/426 368 /434 300/373 404/287 532/ 189

435/ 144 368 /581 300/330 404/ 115 532/440

435/387 368/448 300/404 404/331 532/608

435/428 368 /403 300/ 181 404 / 409 532/ 140

435/296 368 /281 300/357 404/541 532/223

435 / 224 368 /594 300/299 404/411 532/213

435/298 368 /553 300/399 404/217 532 / 222

435/600 368 /580 300/434 404 / 228 532/77

435/475 368 /305 300/581 404/ 188 532/220

435/287 368/98 300/448 404 / 579 532/429

435/ 115 368 /496 300/403 404/ 153 532/447

435/331 368 /532 300/281 404 / 76 532/ 194

435/409 368 /462 300/594 181/357 532/285

435/541 368 / 189 300/553 181/299 532/426

435/411 368/440 300/580 181/399 532/ 144

435/217 368 /608 300/305 181/434 532/387

435/228 368 / 140 300/98 181/581 532/428

435/ 188 368/223 300/496 181/448 532/296

435/579 368 /213 300/532 181/403 532 / 224

435/ 153 368/222 300/462 181/281 532/298

435/76 368/77 300/ 189 181/594 532/600

308/490 368/220 300/440 181/553 532/475

308/ 184 368/429 300/608 181/580 532/287

308/401 368/447 300/ 140 181/305 532/ 115

308/584 368 / 194 300/223 181/98 532/331

308/239 368 /285 300/213 181/496 532/409

308/487 368/426 300 / 222 181/532 532/541

308/550 368 / 144 300/77 181/462 532/411

308/368 368 /387 300/220 181 / 189 532/217

308/372 368/428 300/429 181/440 532/228

308/430 368 /296 300/447 181/608 532/ 188

308/238 368/224 300/ 194 181 / 140 532/579

308/ 186 368 /298 300/285 181/223 532/ 153

308/230 368 /600 300/426 181/213 532/76 Positions Positions Positions Positions Positions

308/543 368 /475 300/ 144 181/222 462/ 189

308/472 368 /287 300/387 181/77 462 / 440

308/464 368 / 115 300/428 181/220 462 / 608

308/546 368 /331 300/296 181/429 462/ 140

308/300 368 /409 300 / 224 181/447 462 / 223

308/549 368 /541 300/298 181 / 194 462/213

308/ 154 368 /411 300/600 181/285 462 / 222

308/453 368 /217 300/475 181/426 462 / 77

308/467 368/228 300/287 181 / 144 462 / 220

308/530 368 / 188 300/ 115 181/387 462 / 429

308/547 368 /579 300/331 181/428 462 / 447

308/348 368 / 153 300/409 181/296 462/ 194

308/568 368/76 300/541 181/224 462/285

308/373 372/430 300/411 181/298 462 / 426

308/330 372/238 300/217 181/600 462/ 144

308/404 372/ 186 300/228 181/475 462/387

308/ 181 372/230 300/ 188 181/287 462 / 428

308/357 372 / 543 300/579 181 / 115 462 / 296

308/299 372 / 472 300/ 153 181/331 462 / 224

308/399 372 / 464 300/76 181/409 462 / 298

308/434 372 / 546 549/ 154 181/541 462 / 600

308/581 372/300 549/453 181/411 462 / 475

308/448 372 / 549 549 / 467 181/217 462/287

308/403 372/ 154 549/530 181/228 462/ 115

308/281 372/453 549 / 547 181 / 188 462/331

308/594 372/467 549/348 181/579 462 / 409

308/553 372/530 549/568 181 / 153 462/541

308/580 372 / 547 549/373 181/76 462/411

308/305 372/348 549/330 357/299 462/217

308 /98 372/568 549 / 404 357/399 462 / 228

308/496 372/373 549/ 181 357/434 462/ 188

308/532 372/330 549/357 357/581 462 / 579

308/462 372 / 404 549 / 299 357/448 462/ 153

308/ 189 372/ 181 549/399 357/403 462 / 76

308/440 372/357 549/434 357/281 189/440

308/608 372/299 549/581 357/594 189/608

308/ 140 372/399 549 / 448 357/553 189/140

308/223 372/434 549 / 403 357/580 189/223

308/213 372/581 549/281 357/305 189/213

308/222 372/448 549 / 594 357/98 189/222

308 /77 372/403 549/553 357/496 189/77 Positions Positions Positions Positions Positions

308/220 372/281 549/580 357/532 189/220

308/429 372 / 594 549/305 357/462 189/429

308/447 372/553 549 / 98 357/ 189 189/447

308/ 194 372/580 549 / 496 357/440 189/194

308/285 372/305 549/532 357/608 189/285

308/426 372/98 549 / 462 357/ 140 189/426

308/ 144 372/496 549/ 189 357/223 189/144

308/387 372/532 549 / 440 357/213 189/387

308/428 372 / 462 549 / 608 357/222 189/428

308/296 372/ 189 549/ 140 357/77 189/296

308/224 372 / 440 549 / 223 357/220 189/224

308/298 372/608 549/213 357/429 189/298

308/600 372/ 140 549 / 222 357/447 189/600

308/475 372 / 223 549 / 77 357/ 194 189/475

308/287 372/213 549 / 220 357/285 189/287

308/ 115 372 / 222 549 / 429 357/426 189/115

308/331 372 / 77 549 / 447 357/ 144 189/331

308/409 372 / 220 549/ 194 357/387 189/409

308/541 372 / 429 549/285 357/428 189/541

308/411 372 / 447 549 / 426 357/296 189/411

308/217 372/ 194 549/ 144 357/224 189/217

308/228 372/285 549/387 357/298 189/228

308/ 188 372 / 426 549 / 428 357/600 189/188

308/579 372/ 144 549 / 296 357/475 189/579

308/ 153 372/387 549 / 224 357/287 189/153

308 /76 372/428 549/298 357/ 115 189/76

490/ 184 372/296 549 / 600 357/331 440 / 608

490/401 372 / 224 549 / 475 357/409 440/ 140

490/584 372/298 549/287 357/541 440 / 223

490/239 372 / 600 549/ 115 357/411 440/213

490/487 372/475 549/331 357/217 440 / 222

490/550 372/287 549 / 409 357/228 440 / 77

490/368 372/ 115 549/541 357/ 188 440 / 220

490 / 372 372/331 549/411 357/579 440 / 429

490/430 372/409 549/217 357/ 153 440 / 447

490/238 372/541 549 / 228 357/76 440/ 194

490/ 186 372/411 549/ 188 299/399 440/285

490/230 372/217 549 / 579 299/434 440 / 426

490 / 543 372/228 549/ 153 299/581 440/ 144

490 / 472 372/ 188 549 / 76 299 / 448 440/387

490 / 464 372/579 154/453 299 / 403 440 / 428 Positions Positions Positions Positions Positions

490 / 546 372/ 153 154/467 299/281 440 / 296

490/300 372 / 76 154/530 299 / 594 440 / 224

490 / 549 430/238 154/547 299/553 440 / 298

490/ 154 430/ 186 154/348 299/580 440 / 600

490/453 430/230 154/568 299/305 440 / 475

490 / 467 430/543 154/373 299 / 98 440/287

490/530 430/472 154/330 299 / 496 440/ 115

490 / 547 430/464 154/404 299/532 440/331

490/348 430/546 154/181 299 / 462 440 / 409

490/568 430/300 154/357 299/ 189 440/541

490/373 430/549 154/299 299 / 440 440/411

490/330 430/ 154 154/399 299 / 608 440/217

490 / 404 430/453 154/434 299/ 140 440 / 228

490/ 181 430/467 154/581 299 / 223 440/ 188

490/357 430/530 154/448 299/213 440 / 579

490 / 299 430/547 154/403 299 / 222 440/ 153

490/399 430/348 154/281 299 / 77 440 / 76

490/434 430/568 154/594 299 / 220 608/ 140

490/581 430/373 154/553 299 / 429 608 / 223

490 / 448 430/330 154/580 299 / 447 608/213

490 / 403 430/404 154/305 299/ 194 608 / 222

490/281 430/ 181 154/98 299/285 608 / 77

490 / 594 430/357 154/496 299 / 426 608 / 220

490/553 430/299 154/532 299 / 144 608 / 429

490/580 430/399 154/462 299/387 608 / 447

490/305 430/434 154/189 299 / 428 608/ 194

490 / 98 430/581 154/440 299 / 296 608/285

490 / 496 430/448 154/608 299 / 224 608 / 426

490/532 430/403 154/140 299/298 608/ 144

490 / 462 430/281 154/223 299 / 600 608/387

490/ 189 430/594 154/213 299 / 475 608/428

490 / 440 430/553 154/222 299/287 608/296

490 / 608 430/580 154/77 299/ 115 608 / 224

490/ 140 430/305 154/220 299/331 608/298

490 / 223 430/98 154/429 299 / 409 608 / 600

490/213 430/496 154/447 299/541 608/475

490 / 222 430/532 154/194 299/411 608/287

490 / 77 430/462 154/285 299/217 608/ 115

490 / 220 430/ 189 154/426 299 / 228 608/331

490 / 429 430/440 154/144 299/ 188 608/409

490 / 447 430/608 154/387 299 / 579 608/541 Positions Positions Positions Positions Positions

490/ 194 430/ 140 154/428 299/ 153 608/411

490/285 430/223 154/296 299 / 76 608/217

490 / 426 430/213 154/224 399/434 608/228

490/ 144 430 / 222 154/298 399/581 608/ 188

490/387 430/77 154/600 399/448 608/579

490 / 428 430/220 154/475 399/403 608/ 153

490 / 296 430/429 154/287 399/281 608 / 76

490 / 224 430/447 154/115 399/594 140/223

490/298 430/ 194 154/331 399/553 140/213

490 / 600 430/285 154/409 399/580 140/222

490 / 475 430/426 154/541 399/305 140/77

490/287 430/ 144 154/411 399/98 140/220

490/ 115 430/387 154/217 399/496 140/429

490/331 430/428 154/228 399/532 140/447

490 / 409 430/296 154/188 399/462 140/194

490/541 430 / 224 154/579 399/ 189 140/285

490/411 430/298 154/153 399/440 140/426

490/217 430/600 154/76 399/608 140/144

490 / 228 430/475 453/467 399/ 140 140/387

490/ 188 430/287 453 /530 399/223 140/428

490 / 579 430/ 115 453 / 547 399/213 140/296

490/ 153 430/331 453 /348 399 / 222 140/224

490 / 76 430/409 453 /568 399/77 140/298

184/401 430/541 453 /373 399/220 140/600

184/584 430/411 453 /330 399/429 140/475

184/239 430/217 453 / 404 399/447 140/287

184/487 430/228 453 / 181 399/ 194 140/115

184/550 430/ 188 453 /357 399/285 140/331

184/368 430/579 453/299 399/426 140/409

184/372 430/ 153 453 /399 399/ 144 140/541

184/430 430/76 453 /434 399/387 140/411

184/238 238 / 186 453 /581 399/428 140/217

184/186 238 /230 453/448 399/296 140/228

184/230 238 /543 453/403 399 / 224 140/188

184/543 238/472 453 /281 399/298 140/579

184/472 238/464 453 / 594 399/600 140/153

184/464 238 /546 453 /553 399/475 140/76

184/546 238 /300 453 /580 399/287 223/213

184/300 238 /549 453 /305 399/ 115 223 / 222

184/549 238 / 154 453 /98 399/331 223 / 77

184/154 238 /453 453/496 399/409 223 / 220 Positions Positions Positions Positions Positions

184/453 238/467 453 /532 399/541 223 / 429

184/467 238 /530 453 / 462 399/411 223 / 447

184/530 238 /547 453 / 189 399/217 223/ 194

184/547 238 /348 453 / 440 399/228 223/285

184/348 238 /568 453/608 399/ 188 223 / 426

184/568 238 /373 453 / 140 399/579 223 / 144

184/373 238 /330 453 / 223 399/ 153 223 /387

184/330 238/404 453/213 399/76 223 / 428

184/404 238 / 181 453 / 222 434/581 223 / 296

184/181 238 /357 453 / 77 434/448 223 / 224

184/357 238/299 453 / 220 434/403 223 / 298

184/299 238 /399 453 / 429 434/281 223 / 600

184/399 238 /434 453 / 447 434 / 594 223 / 475

184/434 238 /581 453/ 194 434/553 223/287

184/581 238/448 453 /285 434/580 223/ 115

184/448 238/403 453 / 426 434/305 223 /331

184/403 238 /281 453 / 144 434/98 223 / 409

184/281 238 /594 453 /387 434/496 223/541

184/594 238 /553 453/428 434/532 223/411

184/553 238 /580 453/296 434 / 462 223/217

184/580 238 /305 453 / 224 434/ 189 223 / 228

184/305 238/98 453/298 434 / 440 223/ 188

184/98 238/496 453 / 600 434/608 223 / 579

184/496 238 /532 453/475 434/ 140 223/ 153

184/532 238/462 453 /287 434 / 223 223 / 76

184/462 238 / 189 453 / 115 434/213 213/222

184/189 238/440 453 /331 434 / 222 213/77

184/440 238 /608 453/409 434 / 77 213/220

184/608 238/ 140 453/541 434 / 220 213/429

184/140 238/223 453/411 434 / 429 213/447

184/223 238/213 453/217 434 / 447 213/194

184/213 238/222 453/228 434/ 194 213/285

184/222 238/77 453 / 188 434/285 213/426

184/77 238/220 453 /579 434 / 426 213/144

184/220 238/429 453 / 153 434/ 144 213/387

184/429 238/447 453 / 76 434/387 213/428

184/447 238 / 194 467/530 434/428 213/296

184/194 238 /285 467 / 547 434/296 213/224

184/285 238/426 467/348 434 / 224 213/298

184/426 238/ 144 467/568 434/298 213/600

184/144 238 /387 467/373 434 / 600 213/475 Positions Positions Positions Positions Positions

184/387 238/428 467/330 434/475 213/287

184/428 238/296 467 / 404 434/287 213/115

184/296 238/224 467/ 181 434/ 115 213/331

184/224 238/298 467/357 434/331 213/409

184/298 238 /600 467 / 299 434/409 213/541

184/600 238/475 467/399 434/541 213/411

184/475 238 /287 467/434 434/411 213/217

184/287 238 / 115 467/581 434/217 213/228

184/115 238 /331 467 / 448 434/228 213/188

184/331 238/409 467 / 403 434/ 188 213/579

184/409 238 /541 467/281 434/579 213/153

184/541 238/411 467 / 594 434/ 153 213/76

184/411 238/217 467/553 434 / 76 222 / 77

184/217 238/228 467/580 581 /448 222 / 220

184/228 238 / 188 467/305 581 /403 222 / 429

184/188 238 /579 467 / 98 581 /281 222 / 447

184/579 238 / 153 467 / 496 581 /594 222/ 194

184/153 238/76 467/532 581 /553 222 / 285

184/76 186/230 467 / 462 581 /580 222 / 426

401 /584 186/543 467/ 189 581 /305 222/ 144

401 /239 186/472 467 / 440 581/98 222/387

401 /487 186/464 467 / 608 581 /496 222 / 428

401 /550 186/546 467/ 140 581 /532 222 / 296

401 /368 186/300 467 / 223 581 /462 222 / 224

401 /372 186/549 467/213 581 / 189 222 / 298

401 /430 186/154 467 / 222 581 /440 222 / 600

401 /238 186/453 467 / 77 581 /608 222 / 475

401 / 186 186/467 467 / 220 581 / 140 222 / 287

401 /230 186/530 467 / 429 581 /223 222/ 115

401 /543 186/547 467 / 447 581/213 222/331

401 /472 186/348 467/ 194 581 /222 222 / 409

401 /464 186/568 467/285 581/77 222/541

401 /546 186/373 467 / 426 581 /220 222/411

401 /300 186/330 467/ 144 581 /429 222/217

401 /549 186/404 467/387 581 /447 222 / 228

401 / 154 186/181 467 / 428 581 / 194 222/ 188

401 /453 186/357 467 / 296 581 /285 222 / 579

401 /467 186/299 467 / 224 581 /426 222/ 153

401 /530 186/399 467/298 581 / 144 222 / 76

401 /547 186/434 467 / 600 581 /387 77 / 220

401 /348 186/581 467 / 475 581 /428 77 / 429 Positions Positions Positions Positions Positions

401 /568 186/448 467/287 581 /296 77 / 447

401 /373 186/403 467/ 115 581 /224 77/194

401 /330 186/281 467/331 581 /298 77/285

401 /404 186/594 467 / 409 581 /600 77 / 426

401 / 181 186/553 467/541 581 /475 77 / 144

401 /357 186/580 467/411 581 /287 77/387

401 /299 186/305 467/217 581 / 115 77 / 428

401 /399 186/98 467 / 228 581 /331 77 / 296

401 /434 186/496 467/ 188 581 /409 77 / 224

401 /581 186/532 467 / 579 581 /541 77/298

401 /448 186/462 467/ 153 581/411 77 / 600

401 /403 186/189 467 / 76 581/217 77 / 475

401 /281 186/440 530/547 581 /228 77/287

401 /594 186/608 530/348 581 / 188 77/115

401 /553 186/140 530/568 581 /579 77/331

401 /580 186/223 530/373 581 / 153 77 / 409

401 /305 186/213 530/330 581/76 77/541

401/98 186/222 530/404 448 / 403 77/411

401 /496 186/77 530/ 181 448/281 77/217

401 /532 186/220 530/357 448 / 594 77 / 228

401 /462 186/429 530/299 448/553 77/188

401 / 189 186/447 530/399 448 /580 77 / 579

401 /440 186/194 530/434 448/305 77/153

401 /608 186/285 530/581 448 / 98 77/76

401 / 140 186/426 530/448 448 / 496 220 / 429

401 /223 186/144 530/403 448 /532 220 / 447

401/213 186/387 530/281 448 / 462 220/ 194

401 /222 186/428 530/594 448/ 189 220/285

401/77 186/296 530/553 448 / 440 220 / 426

401 /220 186/224 530/580 448 / 608 220/ 144

401 /429 186/298 530/305 448 / 140 220/387

401 /447 186/600 530/98 448 / 223 220 / 428

401 / 194 186/475 530/496 448/213 220 / 296

401 /285 186/287 530/532 448 / 222 220 / 224

401 /426 186/115 530/462 448 / 77 220 / 298

401 / 144 186/331 530/ 189 448 / 220 220 / 600

401 /387 186/409 530/440 448 / 429 220 / 475

401 /428 186/541 530/608 448 / 447 220/287

401 /296 186/411 530/ 140 448/ 194 220/ 115

401 /224 186/217 530/223 448/285 220/331

401 /298 186/228 530/213 448 / 426 220 / 409 Positions Positions Positions Positions Positions

401 /600 186/188 530/222 448 / 144 220/541

401 /475 186/579 530/77 448 /387 220/411

401 /287 186/153 530/220 448 / 428 220/217

401 / 115 186/76 530/429 448 / 296 220 / 228

401 /331 230/543 530/447 448 / 224 220/ 188

401 /409 230/472 530/ 194 448/298 220 / 579

401 /541 230/464 530/285 448 / 600 220/ 153

401/411 230/546 530/426 448 / 475 220 / 76

401/217 230/300 530/ 144 448/287 429 / 447

401 /228 230/549 530/387 448/ 115 429/ 194

401 / 188 230/ 154 530/428 448 /331 429/285

401 /579 230/453 530/296 448 / 409 429 / 426

401 / 153 230/467 530/224 448/541 429/ 144

401/76 230/530 530/298 448/411 429/387

584/239 230/547 530/600 448/217 429 / 428

584/487 230/348 530/475 448 / 228 429 / 296

584/550 230/568 530/287 448/ 188 429 / 224

584/368 230/373 530/ 115 448 / 579 429 / 298

584/372 230/330 530/331 448/ 153 429 / 600

584/430 230/404 530/409 448 / 76 429 / 475

584/238 230/ 181 530/541 403 /281 429/287

584/ 186 230/357 530/411 403 / 594 429/ 115

584/230 230/299 530/217 403 /553 429/331

584/543 230/399 530/228 403 /580 429 / 409

584/472 230/434 530/ 188 403 /305 429/541

584/464 230/581 530/579 403 / 98 429/411

584/546 230/448 530/ 153 403 / 496 429/217

584/300 230/403 530/76 403 /532 429 / 228

584/549 230/281 547/348 403 / 462 429/ 188

584/ 154 230/594 547/568 403 / 189 429 / 579

584/453 230/553 547/373 403 / 440 429/ 153

584/467 230/580 547/330 403 / 608 429 / 76

584/530 230/305 547 / 404 403 / 140 447/ 194

584/547 230/98 547/ 181 403 / 223 447/285

584/348 230/496 547/357 403 /213 447 / 426

584/568 230/532 547 / 299 403 / 222 447/ 144

584/373 230/462 547/399 403 / 77 447/387

584/330 230/ 189 547/434 403 / 220 447 / 428

584/404 230/440 547/581 403 / 429 447 / 296

584/ 181 230/608 547 / 448 403 / 447 447 / 224

584/357 230/ 140 547 / 403 403 / 194 447 / 298 Positions Positions Positions Positions Positions

584/299 230/223 547/281 403 /285 447 / 600

584/399 230/213 547 / 594 403 / 426 447 / 475

584/434 230 / 222 547/553 403 / 144 447/287

584/581 230/77 547/580 403 /387 447/ 115

584/448 230/220 547/305 403 / 428 447/331

584/403 230/429 547 / 98 403 / 296 447 / 409

584/281 230/447 547 / 496 403 / 224 447/541

584/594 230/ 194 547/532 403 /298 447/411

584/553 230/285 547 / 462 403 / 600 447/217

584/580 230/426 547/ 189 403 / 475 447 / 228

584/305 230/ 144 547 / 440 403 /287 447/ 188

584/98 230/387 547 / 608 403 / 115 447 / 579

584/496 230/428 547/ 140 403 /331 447/ 153

584/532 230/296 547 / 223 403 / 409 447 / 76

584/462 230 / 224 547/213 403 /541 194/285

584/ 189 230/298 547 / 222 403 /411 194/426

584/440 230/600 547 / 77 403 /217 194/144

584/608 230/475 547 / 220 403 / 228 194/387

584/ 140 230/287 547 / 429 403 / 188 194/428

584/223 230/ 115 547 / 447 403 / 579 194/296

584/213 230/331 547/ 194 403 / 153 194/224

584 / 222 230/409 547/285 403 / 76 194/298

584/77 230/541 547 / 426 281 /594 194/600

584/220 230/411 547/ 144 281 /553 194/475

584/429 230/217 547/387 281 /580 194/287

584/447 230/228 547 / 428 281 /305 194/115

584/ 194 230/ 188 547 / 296 281/98 194/331

584/285 230/579 547 / 224 281 /496 194/409

584/426 230/ 153 547/298 281 /532 194/541

584/ 144 230/76 547 / 600 281 /462 194/411

584/387 543 / 472 547 / 475 281 / 189 194/217

584/428 543 / 464 547/287 281 /440 194/228

584/296 543 / 546 547/ 115 281 /608 194/188

584 / 224 543 /300 547/331 281 / 140 194/579

584/298 543 / 549 547 / 409 281 /223 194/153

584/600 543 / 154 547/541 281/213 194/76

584/475 543 /453 547/411 281 /222 285/426

584/287 543 / 467 547/217 281/77 285/ 144

584/ 115 543 /530 547 / 228 281 /220 285/387

584/331 543 / 547 547/ 188 281 /429 285/428

584/409 543 /348 547 / 579 281 /447 285/296 Positions Positions Positions Positions Positions

584/541 543 /568 547/ 153 281 / 194 285 / 224

584/411 543 /373 547 / 76 281 /285 285/298

584/217 543 /330 348/568 281 /426 285/600

584/228 543 / 404 348/373 281 / 144 285/475

584/ 188 543 / 181 348/330 281 /387 285/287

584/579 543 /357 348/404 281 /428 285/ 115

584/ 153 543 / 299 348/ 181 281 /296 285/331

584/76 543 /399 348/357 281 /224 285/409

239/487 543 /434 348/299 281 /298 285/541

239/550 543 /581 348/399 281 /600 285/411

239/368 543 / 448 348/434 281 /475 285/217

239/372 543 / 403 348/581 281 /287 285/228

239/430 543 /281 348/448 281 / 115 285/ 188

239/238 543 / 594 348/403 281 /331 285/579

239/ 186 543 /553 348/281 281 /409 285/ 153

239/230 543 /580 348/594 281 /541 285/76

239/543 543 /305 348/553 281/411 426/ 144

239/472 543 / 98 348/580 281/217 426/387

239/464 543 / 496 348/305 281 /228 426 / 428

239/546 543 /532 348 /98 281 / 188 426 / 296

239/300 543 / 462 348/496 281 /579 426 / 224

239/549 543 / 189 348/532 281 / 153 426 / 298

239/ 154 543 / 440 348/462 281/76 426 / 600

239/453 543 / 608 348/ 189 594/553 426 / 475

239/467 543 / 140 348/440 594/580 426/287

239/530 543 / 223 348/608 594/305 426/ 115

239/547 543 /213 348/ 140 594 / 98 426/331

239/348 543 / 222 348/223 594 / 496 426 / 409

239/568 543 / 77 348/213 594/532 426/541

239/373 543 / 220 348 / 222 594 / 462 426/411

239/330 543 / 429 348 /77 594/ 189 426/217

239/404 543 / 447 348/220 594 / 440 426 / 228

239/ 181 543 / 194 348/429 594 / 608 426/ 188

239/357 543 /285 348/447 594/ 140 426 / 579

239/299 543 / 426 348/ 194 594 / 223 426/ 153

239/399 543 / 144 348/285 594/213 426 / 76

239/434 543 /387 348/426 594 / 222 144/387

239/581 543 / 428 348/ 144 594 / 77 144/428

239/448 543 / 296 348/387 594 / 220 144/296

239/403 543 / 224 348/428 594 / 429 144/224

239/281 543 /298 348/296 594 / 447 144/298 Positions Positions Positions Positions Positions

239/594 543 / 600 348 / 224 594/ 194 144/600

239/553 543 / 475 348/298 594/285 144/475

239/580 543 /287 348/600 594 / 426 144/287

239/305 543 / 115 348/475 594 / 144 144/115

239/98 543 /331 348/287 594/387 144/331

239/496 543 / 409 348/ 115 594 / 428 144/409

239/532 543 /541 348/331 594 / 296 144/541

239/462 543 /411 348/409 594 / 224 144/411

239/ 189 543 /217 348/541 594/298 144/217

239/440 543 / 228 348/411 594 / 600 144/228

239/608 543 / 188 348/217 594 / 475 144/188

239/ 140 543 / 579 348/228 594/287 144/579

239/223 543 / 153 348/ 188 594/ 115 144/153

239/213 543 / 76 348/579 594/331 144/76

239 / 222 472 / 464 348/ 153 594 / 409 387/428

239/77 472 / 546 348 /76 594/541 387/296

239/220 472 / 300 568/373 594/411 387/224

239/429 472 / 549 568/330 594/217 387/298

239/447 472/ 154 568/404 594 / 228 387/600

239/ 194 472 / 453 568/ 181 594/ 188 387/475

239/285 472 / 467 568/357 594 / 579 387/287

239/426 472/530 568/299 594/ 153 387/ 115

239/ 144 472 / 547 568/399 594 / 76 387/331

239/387 472 / 348 568/434 553 /580 387/409

239/428 472 / 568 568/581 553 /305 387/541

239/296 472 / 373 568/448 553 /98 387/411

239 / 224 472/330 568/403 553 /496 387/217

239/298 472 / 404 568/281 553 /532 387/228

239/600 472/ 181 568/594 553 /462 387/ 188

239/475 472/357 568/553 553 / 189 387/579

239/287 472 / 299 568/580 553 /440 387/ 153

239/ 115 472 / 399 568/305 553 /608 387/76

239/331 472 / 434 568 /98 553 / 140 428 / 296

239/409 472/581 568/496 553 /223 428 / 224

239/541 472 / 448 568/532 553 /213 428/298

239/411 472 / 403 568/462 553 / 222 428 / 600

239/217 472/281 568/ 189 553 /77 428 / 475

239/228 472 / 594 568/440 553 /220 428/287

239/ 188 472 / 553 568/608 553 /429 428/ 115

239/579 472/580 568/ 140 553 /447 428/331

239/ 153 472 / 305 568/223 553 / 194 428 / 409 Positions Positions Positions Positions Positions

239/76 472 / 98 568/213 553 /285 428/541

487/550 472 / 496 568 / 222 553 /426 428/411

487/368 472 / 532 568 /77 553 / 144 428/217

487/372 472 / 462 568/220 553 /387 428 / 228

487/430 472/ 189 568/429 553 /428 428/ 188

487/238 472 / 440 568/447 553 /296 428 / 579

487/ 186 472 / 608 568/ 194 553 / 224 428/ 153

487/230 472 / 140 568/285 553 /298 428 / 76

487/543 472 / 223 568/426 553 /600 296 / 224

487/472 472/213 568/ 144 553 /475 296/298

487/464 472 / 222 568/387 553 /287 296 / 600

487/546 472 / 77 568/428 553 / 115 296 / 475

487/300 472 / 220 568/296 553 /331 296/287

487/549 472 / 429 568 / 224 553 /409 296/ 115

487/ 154 472 / 447 568/298 553 /541 296/331

487/453 472/ 194 568/600 553 /411 296 / 409

487/467 472/285 568/475 553 /217 296/541

487/530 472 / 426 568/287 553 /228 296/411

487/547 472 / 144 568/ 115 553 / 188 296/217

487/348 472/387 568/331 553 /579 296 / 228

487/568 472 / 428 568/409 553 / 153 296/ 188

487/373 472 / 296 568/541 553 /76 296 / 579

487/330 472 / 224 568/411 580/305 296/ 153

487/404 472 / 298 568/217 580/98 296 / 76

487/ 181 472 / 600 568/228 580/496 224 / 298

487/357 472 / 475 568/ 188 580/532 224 / 600

487/299 472/287 568/579 580/462 224 / 475

487/399 472/ 115 568/ 153 580/ 189 224 / 287

487/434 472/331 568 /76 580/440 224/ 115

487/581 472 / 409 373 /330 580/608 224/331

487/448 472/541 373 /404 580/ 140 224 / 409

487/403 472/411 373 / 181 580/223 224/541

487/281 472/217 373 /357 580/213 224/411

487/594 472 / 228 373 /299 580/222 224/217

487/553 472/ 188 373 /399 580/77 224 / 228

487/580 472 / 579 373 /434 580/220 224/ 188

487/305 472/ 153 373 /581 580/429 224 / 579

487/98 472 / 76 373/448 580/447 224/ 153

487/496 464 / 546 373 /403 580/ 194 224 / 76

487/532 464 / 300 373 /281 580/285 298 / 600

487/462 464 / 549 373 /594 580/426 298/475 Positions Positions Positions Positions Positions

487/ 189 464/ 154 373 /553 580/ 144 298/287

487/440 464 / 453 373 /580 580/387 298/ 115

487/608 464 / 467 373 /305 580/428 298/331

487/ 140 464/530 373 /98 580/296 298/409

487/223 464 / 547 373 /496 580/224 298/541

487/213 464 / 348 373 /532 580/298 298/411

487 / 222 464 / 568 373 /462 580/600 298/217

487/77 464 / 373 373 / 189 580/475 298/228

487/220 464/330 373/440 580/287 298/ 188

487/429 464 / 404 373 /608 580/ 115 298/579

487/447 464/ 181 373 / 140 580/331 298/ 153

487/ 194 464/357 373/223 580/409 298 / 76

487/285 464 / 299 373 /213 580/541 600 / 475

487/426 464 / 399 373 / 222 580/411 600/287

487/ 144 464 / 434 373 /77 580/217 600/ 115

487/387 464/581 373/220 580/228 600/331

487/428 464 / 448 373/429 580/ 188 600 / 409

487/296 464 / 403 373/447 580/579 600/541

487 / 224 464/281 373 / 194 580/ 153 600/411

487/298 464 / 594 373 /285 580/76 600/217

487/600 464 / 553 373/426 305/98 600 / 228

487/475 464/580 373 / 144 305/496 600/ 188

487/287 464 / 305 373 /387 305 /532 600 / 579

487/ 115 464 / 98 373/428 305/462 600/ 153

487/331 464 / 496 373 /296 305 / 189 600 / 76

487/409 464 / 532 373 / 224 305/440 475/287

487/541 464 / 462 373 /298 305 /608 475/ 115

487/411 464/ 189 373 /600 305/ 140 475/331

487/217 464 / 440 373 /475 305/223 475 / 409

487/228 464 / 608 373 /287 305/213 475/541

487/ 188 464 / 140 373 / 115 305 / 222 475/411

487/579 464 / 223 373 /331 305/77 475/217

487/ 153 464/213 373 /409 305/220 475 / 228

487/76 464 / 222 373 /541 305/429 475/ 188

550/368 464 / 77 373 /411 305/447 475 / 579

550/372 464 / 220 373 /217 305 / 194 475/ 153

550/430 464 / 429 373/228 305 /285 475 / 76

550/238 464 / 447 373 / 188 305/426 287/ 115

550/ 186 464/ 194 373 /579 305 / 144 287/331

550/230 464/285 373 / 153 305 /387 287/409

550/543 464 / 426 373 /76 305/428 287/541 Positions Positions Positions Positions Positions

550/472 464 / 144 330/404 305/296 287/411

550/464 464/387 330/ 181 305 / 224 287/217

550/546 464 / 428 330/357 305/298 287/228

550/300 464 / 296 330/299 305 /600 287/ 188

550/549 464 / 224 330/399 305/475 287/579

550/ 154 464 / 298 330/434 305 /287 287/ 153

550/453 464 / 600 330/581 305 / 115 287/76

550/467 464 / 475 330/448 305 /331 115/331

550/530 464/287 330/403 305/409 115/409

550/547 464/ 115 330/281 305 /541 115/541

550/348 464/331 330/594 305/411 115/411

550/568 464 / 409 330/553 305/217 115/217

550/373 464/541 330/580 305/228 115/228

550/330 464/411 330/305 305 / 188 115/188

550/404 464/217 330/98 305 /579 115/579

550/ 181 464 / 228 330/496 305 / 153 115/153

550/357 464/ 188 330/532 305/76 115/76

550/299 464 / 579 330/462 98/496 331 /409

550/399 464/ 153 330/ 189 98/532 331 /541

550/434 464 / 76 330/440 98 / 462 331/411

550/581 546/300 330/608 98/189 331/217

550/448 546 / 549 330/ 140 98 / 440 331 /228

550/403 546/ 154 330/223 98/608 331 / 188

550/281 546/453 330/213 98/140 331 /579

550/594 546 / 467 330/222 98 / 223 331 / 153

550/553 546/530 330/77 98/213 331/76

550/580 546 / 547 330/220 98 / 222 409/541

550/305 546/348 330/429 98/77 409/411

550/98 546/568 330/447 98 / 220 409/217

550/496 546/373 330/ 194 98 / 429 409 / 228

550/532 546/330 330/285 98 / 447 409/ 188

550/462 546 / 404 330/426 98/194 409 / 579

550/ 189 546/ 181 330/ 144 98/285 409/ 153

550/440 546/357 330/387 98 / 426 409 / 76

550/608 546 / 299 330/428 98/144 541/411

550/ 140 546/399 330/296 98/387 541/217

550/223 546/434 330/224 98/428 541 /228

550/213 546/581 330/298 98/296 541 / 188

550 / 222 546 / 448 330/600 98 / 224 541 /579

550/77 546 / 403 330/475 98 / 298 541 / 153

550/220 546/281 330/287 98 / 600 541/76 Positions Positions Positions Positions Positions

550/429 546 / 594 330/ 115 98/475 411/217

550/447 546/553 330/331 98/287 411/228

550/ 194 546/580 330/409 98/115 411 / 188

550/285 546/305 330/541 98/331 411/579

550/426 546 / 98 330/411 98 / 409 411 / 153

550/ 144 546 / 496 330/217 98/541 411/76

550/387 546/532 330/228 98/411 217/228

550/428 546 / 462 330/ 188 98/217 217/188

550/296 546/ 189 330/579 98/228 217/579

550 / 224 546 / 440 330/ 153 98/188 217/153

550/298 546 / 608 330/76 98/579 217/76

550/600 546/ 140 404/ 181 98/153 228/ 188

550/475 546 / 223 404/357 98/76 228 / 579

550/287 546/213 404 / 299 496/532 228/ 153

550/ 115 546 / 222 404 / 399 496 / 462 228 / 76

550/331 546 / 77 404 / 434 496/ 189 188/579

550/409 546 / 220 404/581 496 / 440 188/153

550/541 546 / 429 404 / 448 496 / 608 188/76

550/411 546 / 447 404 / 403 496/ 140 579/ 153

550/217 546/ 194 404/281 496 / 223 579 / 76

550/228 546/285 404 / 594 496/213 153/76

550/ 188 546 / 426 404 / 553 496 / 222

550/579 546 / 144 404/580 496 / 77

550/ 153 546/387 404 / 305 496 / 220

550/76 546 / 428 404 / 98 496 / 429

368/372 546 / 296 404 / 496 496 / 447

368/430 546 / 224 404 / 532 496/ 194

368/238 546/298 404 / 462 496/285

368/ 186 546 / 600 404/ 189 496 / 426

368/230 546 / 475 404 / 440 496 / 144

368/543 546/287 404 / 608 496/387

368/472 546/ 115 404/ 140 496 / 428

368/464 546/331 404 / 223 496 / 296

368/546 546 / 409 404/213 496 / 224

368/300 546/541 404 / 222 496/298

368/549 546/411 404 / 77 496 / 600

368/ 154 546/217 404 / 220 496 / 475

368/453 546 / 228 404 / 429 496/287

368/467 546/ 188 404 / 447 496/ 115

368/530 546 / 579 404/ 194 496/331

368/547 546/ 153 404/285 496 / 409 Positions Positions Positions Positions Positions

368/348 546 / 76 404 / 426 496/541

368/568 300/549 404/ 144 496/411

368/373 300/ 154 404/387 496/217

368/330 300/453 404 / 428 496 / 228

368/404 300/467 404 / 296 496/ 188

In some embodiments, the identity and position of the two amino acids being substituted may be selected from Table 4. In certain embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 pairs of mutations from Table 4 are combined in one nucleic acid molecule encoding a MT polypeptide of the instant disclosure. In particular cases, amino acid substitutions or combinations thereof may be selected from Table 4, or conservative amino acid substitutions of the substitutions as shown in Table 4.

Table 4. Pairwise Combinations of Specific Amino Acid Substitutions

Positions Positions Positions Positions Positions

L249M/F335L V165A/I76L M319V/S87Q I287L/F347I C282S/E240A

L249M/T248A V165A/I76M M319V/L98H I287L/V221F C282S/E240T

L249M/T248D V165A/G138K M319V/S70K I287L/V221I C282S/N148H

L249M/L284S V165A/L238F M319V/F351A I287L/G245S C282S/F94L

L249M/N350K V165A/L238T M319V/F351V I287L/Q92C C282S/F94Y

L249M/N350R V165A/I35L M319V/M157Y I287L/Q92S C282S/V150L

L249M/F132L V165A/I35V M319V/C44F I287L/F230A C282S/F68P

L249M/I287L V165A/C208A M319V/C44Y I287L/F230N C282S/N148R

L249M/V36I V165A/C208S M319V/I3L I287L/S87P C282S/K361R

L249M/V36L V165A/E240A M319V/I3M I287L/S87Q C282S/Q280E

L249M/H131V V165A/E240T G245A/G245C I287L/L98H C282S/Q280R

L249M/H131Y V165A/N148H G245A/C282E I287L/S70K C282S/K225E

L249M/S243E V165A/F94L G245A/C282I I287L/F351A C282S/K225G

L249M/I211L V165A/F94Y G245A/F335L I287L/F351V C282S/L238A

L249M/I211V V165A/V150L G245A/T248A I287L/M157Y C282S/L238S

L249M/I91F V165A/F68P G245A/T248D I287L/C44F C282S/C269A

L249M/E360G V165A/N148R G245A/L284S I287L/C44Y C282S/C269I

L249M/E360L V165A/K361R G245A/N350K I287L/I3L C282S/D296P

L249M/A315R V165A/Q280E G245A/N350R I287L/I3M C282S/F140Y

L249M/A315S V165A/Q280R G245A/F132L V36I/V36L C282S/I24L

L249M/C282S V165A/K225E G245A/I287L V36I/H131V C282S/I24V

L249M/C282V V165A/K225G G245A/V36I V36I/H131Y C282S/D170S

L249M/G135A V165A/L238A G245A/V36L V36I/S243E C282S/V229M

L249M/V221C V165A/L238S G245A/H131V V36I/I211L C282S/E360A

L249M/V221M V165A/C269A G245A/H131Y V36I/I211V C282S/S322V

L249M/R247M V165A/C269I G245A/S243E V36I/I91F C282S/F347I

L249M/R247N V165A/D296P G245A/I211L V36I/E360G C282S/V221F

L249M/I91L V165A/F140Y G245A/I211V V36I/E360L C282S/V221I

L249M/I91V V165A/I24L G245A/I91F V36I/A315R C282S/G245S

L249M/M160H V165A/I24V G245A/E360G V36I/A315S C282S/Q92C

L249M/L293F V165A/D170S G245A/E360L V36I/C282S C282S/Q92S

L249M/L293S V165A/V229M G245A/A315R V36I/C282V C282S/F230A

L249M/L66F V165A/E360A G245A/A315S V36I/G135A C282S/F230N

L249M/C282D V165A/S322V G245A/C282S V36I/V221C C282S/S87P

L249M/A222H V165A/F347I G245A/C282V V36I/V221M C282S/S87Q

L249M/A222L V165A/V221F G245A/G135A V36I/R247M C282S/L98H

L249M/E356S V165A/V221I G245A/V221C V36I/R247N C282S/S70K

L249M/S109G V165A/G245S G245A/V221M V36I/I91L C282S/F351A

L249M/I290L V165A/Q92C G245A/R247M V36I/I91V C282S/F351V

L249M/I290M V165A/Q92S G245A/R247N V36I/M160H C282S/M157Y

L249M/L330M V165A/F230A G245A/I91L V36I/L293F C282S/C44F

L249M/H131C V165A/F230N G245A/I91V V36I/L293S C282S/C44Y Positions Positions Positions Positions Positions

L249M/A189G V165A/ S87P G245A/M160H V36I/L66F C282S /I3L

L249M/Q193K V165A/ S87Q G245A/L293F V36I/C282D C282S /I3M

L249M/Q193R V165A/L98H G245A/L293S V36I/A222H C282V/G135A

L249M/L242I V165A/ S70K G245A/L66F V36I/A222L C282V/V221C

L249M/Q108H V165A/F351A G245A/C282D V36I/E356S C282V/V221M

L249M/F68V V165A/F351V G245A/A222H V36I/ S 109G C282V/R247M

L249M/G100S V165A/M157Y G245A/A222L V36I/I290L C282V/R247N

L249M/G100T V165A/C44F G245A/E356S V36I/I290M C282V/I91L

L249M/L323I V165A/C44Y G245A/ S 109G V36I/L330M C282V/I91V

L249M/L323M V165A/I3L G245A/I290L V36I/H131C C282V/M160H

L249M/Q277D V165A/I3M G245A/I290M V36I/A189G C282V/L293F

L249M/Q277E V218F/N96S G245A/L330M V36I/Q193K C282V/L293S

L249M/C269N V218F/F347Y G245A/H131C V36I/Q193R C282V/L66F

L249M/C269T V218F/M206C G245A/A189G V36I/L242I C282V/C282D

L249M/A326F V218F/M206L G245A/Q193K V36I/Q108H C282V/A222H

L249M/A326I V218F/P129V G245A/Q193R V36I/F68V C282V/A222L

L249M/L152F V218F/T65A G245A/L242I V36I/G100S C282V/E356S

L249M/C282N V218F/I106V G245A/Q108H V36I/G100T C282V/ S109G

L249M/ S329P V218F/P186Q G245A/F68V V36I/L323I C282V/I290L

L249M/I45D V218F/M319I G245A/G100S V36I/L323M C282V/I290M

L249M/I45L V218F/M319V G245A/G100T V36I/Q277D C282V/L330M

L249M/E258A V218F/G245A G245A/L323I V36I/Q277E C282V/H131C

L249M/A272E V218F/G245C G245A/L323M V36I/C269N C282V/A189G

L249M/T312A V218F/C282E G245A/Q277D V36I/C269T C282V/Q193K

L249M/T312R V218F/C282I G245A/Q277E V36I/A326F C282V/Q193R

L249M/M327Q V218F/F335L G245A/C269N V36I/A326I C282V/L242I

L249M/M327T V218F/T248A G245A/C269T V36I/L152F C282V/Q108H

L249M/N174Y V218F/T248D G245A/A326F V36I/C282N C282V/F68V

L249M/L340I V218F/L284S G245A/A326I V36I/ S329P C282V/G100S

L249M/L340M V218F/N350K G245A/L152F V36I/I45D C282V/G100T

L249M/A189H V218F/N350R G245A/C282N V36I/I45L C282V/L323I

L249M/A189Y V218F/F132L G245A/ S329P V36I/E258A C282V/L323M

L249M/N194R V218F/I287L G245A/I45D V36I/A272E C282V/Q277D

L249M/N194S V218F/V36I G245A/I45L V36I/T312A C282V/Q277E

L249M/L169V V218F/V36L G245A/E258A V36I/T312R C282V/C269N

L249M/K225D V218F/H131V G245A/A272E V36I/M327Q C282V/C269T

L249M/K225S V218F/H131Y G245A/T312A V36I/M327T C282V/A326F

L249M/A63I V218F/ S243E G245A/T312R V36I/N174Y C282V/A326I

L249M/A63P V218F/I21 1L G245A/M327Q V36I/L340I C282V/L152F

L249M/I180L V218F/I21 1V G245A/M327T V36I/L340M C282V/C282N

L249M/I180V V218F/I91F G245A/N174Y V36I/A189H C282V/ S329P

L249M/H151D V218F/E360G G245A/L340I V36I/A189Y C282V/I45D Positions Positions Positions Positions Positions

L249M/T220I V218F/E360L G245A/L340M V36I/N194R C282V/I45L

L249M/T220S V218F/A315R G245A/A189H V36I/N194S C282V/E258A

L249M/L246I V218F/A315S G245A/A189Y V36I/L169V C282V/A272E

L249M/A272P V218F/C282S G245A/N194R V36I/K225D C282V/T312A

L249M/ S353E V218F/C282V G245A/N194S V36I/K225S C282V/T312R

L249M/ S353K V218F/G135A G245A/L169V V36I/A63I C282V/M327Q

L249M/A256D V218F/V221C G245A/K225D V36I/A63P C282V/M327T

L249M/A256E V218F/V221M G245A/K225S V36I/I180L C282V/N174Y

L249M/R224L V218F/R247M G245A/A63I V36I/I180V C282V/L340I

L249M/A134M V218F/R247N G245A/A63P V36I/H151D C282V/L340M

L249M/V359E V218F/I91L G245A/I180L V36I/T220I C282V/A189H

L249M/V359K V218F/I91V G245A/I180V V36I/T220S C282V/A189Y

L249M/ S333A V218F/M160H G245A/H151D V36I/L246I C282V/N194R

L249M/ S333E V218F/L293F G245A/T220I V36I/A272P C282V/N194S

L249M/T352D V218F/L293S G245A/T220S V36I/ S353E C282V/L169V

L249M/T352E V218F/L66F G245A/L246I V36I/ S353K C282V/K225D

L249M/M157F V218F/C282D G245A/A272P V36I/A256D C282V/K225S

L249M/M157S V218F/A222H G245A/ S353E V36I/A256E C282V/A63I

L249M/D14G V218F/A222L G245A/ S353K V36I/R224L C282V/A63P

L249M/D296A V218F/E356S G245A/A256D V36I/A134M C282V/I180L

L249M/D296L V218F/ S109G G245A/A256E V36I/V359E C282V/I180V

L249M/T314A V218F/I290L G245A/R224L V36I/V359K C282V/H151D

L249M/T314E V218F/I290M G245A/A134M V36I/ S333A C282V/T220I

L249M/F267Y V218F/L330M G245A/V359E V36I/ S333E C282V/T220S

L249M/E71N V218F/H131C G245A/V359K V36I/T352D C282V/L246I

L249M/E252Q V218F/A189G G245A/ S333A V36I/T352E C282V/A272P

L249M/I367V V218F/Q193K G245A/ S333E V36I/M157F C282V/ S353E

L249M/A31M V218F/Q193R G245A/T352D V36I/M157S C282V/ S353K

L249M/A31 S V218F/L242I G245A/T352E V36I/D14G C282V/A256D

L249M/F93A V218F/Q108H G245A/M157F V36I/D296A C282V/A256E

L249M/L323C V218F/F68V G245A/M157S V36I/D296L C282V/R224L

L249M/L323V V218F/G100S G245A/D14G V36I/T314A C282V/A134M

L249M/T83G V218F/G100T G245A/D296A V36I/T314E C282V/V359E

L249M/T83N V218F/L323I G245A/D296L V36I/F267Y C282V/V359K

L249M/Q92R V218F/L323M G245A/T314A V36I/E71N C282V/ S333A

L249M/F267I V218F/Q277D G245A/T314E V36I/E252Q C282V/ S333E

L249M/F267Q V218F/Q277E G245A/F267Y V36I/I367V C282V/T352D

L249M/E4K V218F/C269N G245A/E71N V36I/A31M C282V/T352E

L249M/E90D V218F/C269T G245A/E252Q V36I/A31 S C282V/M157F

L249M/T312K V218F/A326F G245A/I367V V36I/F93A C282V/M157S

L249M/T312N V218F/A326I G245A/A31M V36I/L323C C282V/D14G

L249M/L241V V218F/L152F G245A/A31 S V36I/L323V C282V/D296A Positions Positions Positions Positions Positions

L249M/V255I V218F/C282N G245A/F93A V36I/T83G C282V/D296L

L249M/F344G V218F/ S329P G245A/L323C V36I/T83N C282V/T314A

L249M/I76L V218F/I45D G245A/L323V V36I/Q92R C282V/T314E

L249M/I76M V218F/I45L G245A/T83G V36I/F267I C282V/F267Y

L249M/G138K V218F/E258A G245A/T83N V36I/F267Q C282V/E71N

L249M/L238F V218F/A272E G245A/Q92R V36I/E4K C282V/E252Q

L249M/L238T V218F/T312A G245A/F267I V36I/E90D C282V/I367V

L249M/I35L V218F/T312R G245A/F267Q V36I/T312K C282V/A31M

L249M/I35V V218F/M327Q G245A/E4K V36I/T312N C282V/A31 S

L249M/C208A V218F/M327T G245A/E90D V36I/L241V C282V/F93A

L249M/C208S V218F/N174Y G245A/T312K V36I/V255I C282V/L323C

L249M/E240A V218F/L340I G245A/T312N V36I/F344G C282V/L323V

L249M/E240T V218F/L340M G245A/L241V V36I/I76L C282V/T83G

L249M/N148H V218F/A189H G245A/V255I V36I/I76M C282V/T83N

L249M/F94L V218F/A189Y G245A/F344G V36I/G138K C282V/Q92R

L249M/F94Y V218F/N194R G245A/I76L V36I/L238F C282V/F267I

L249M/V150L V218F/N194S G245A/I76M V36I/L238T C282V/F267Q

L249M/F68P V218F/L169V G245A/G138K V36I/I35L C282V/E4K

L249M/N148R V218F/K225D G245A/L238F V36I/I35V C282V/E90D

L249M/K361R V218F/K225S G245A/L238T V36I/C208A C282V/T312K

L249M/Q280E V218F/A63I G245A/I35L V36I/C208S C282V/T312N

L249M/Q280R V218F/A63P G245A/I35V V36I/E240A C282V/L241V

L249M/K225E V218F/I180L G245A/C208A V36I/E240T C282V/V255I

L249M/K225G V218F/I180V G245A/C208S V36I/N148H C282V/F344G

L249M/L238A V218F/H151D G245A/E240A V36I/F94L C282V/I76L

L249M/L238S V218F/T220I G245A/E240T V36I/F94Y C282V/I76M

L249M/C269A V218F/T220S G245A/N148H V36I/V150L C282V/G138K

L249M/C269I V218F/L246I G245A/F94L V36I/F68P C282V/L238F

L249M/D296P V218F/A272P G245A/F94Y V36I/N148R C282V/L238T

L249M/F140Y V218F/ S353E G245A/V150L V36I/K361R C282V/I35L

L249M/I24L V218F/ S353K G245A/F68P V36I/Q280E C282V/I35V

L249M/I24V V218F/A256D G245A/N148R V36I/Q280R C282V/C208A

L249M/D170S V218F/A256E G245A/K361R V36I/K225E C282V/C208S

L249M/V229M V218F/R224L G245A/Q280E V36I/K225G C282V/E240A

L249M/E360A V218F/A134M G245A/Q280R V36I/L238A C282V/E240T

L249M/ S322V V218F/V359E G245A/K225E V36I/L238S C282V/N148H

L249M/F347I V218F/V359K G245A/K225G V36I/C269A C282V/F94L

L249M/V221F V218F/ S333A G245A/L238A V36I/C269I C282V/F94Y

L249M/V221I V218F/ S333E G245A/L238S V36I/D296P C282V/V150L

L249M/G245S V218F/T352D G245A/C269A V36I/F140Y C282V/F68P

L249M/Q92C V218F/T352E G245A/C269I V36I/I24L C282V/N148R

L249M/Q92S V218F/M157F G245A/D296P V36I/I24V C282V/K361R Positions Positions Positions Positions Positions

L249M/F230A V218F/M157S G245A/F140Y V36I/D170S C282V/Q280E

L249M/F230N V218F/D14G G245A/I24L V36I/V229M C282V/Q280R

L249M/ S87P V218F/D296A G245A/I24V V36I/E360A C282V/K225E

L249M/ S87Q V218F/D296L G245A/D170S V36I/ S322V C282V/K225G

L249M/L98H V218F/T314A G245A/V229M V36I/F347I C282V/L238A

L249M/ S70K V218F/T314E G245A/E360A V36I/V221F C282V/L238S

L249M/F351A V218F/F267Y G245A/ S322V V36I/V221I C282V/C269A

L249M/F351V V218F/E71N G245A/F347I V36I/G245S C282V/C269I

L249M/M157Y V218F/E252Q G245A/V221F V36I/Q92C C282V/D296P

L249M/C44F V218F/I367V G245A/V221I V36I/Q92S C282V/F140Y

L249M/C44Y V218F/A31M G245A/G245S V36I/F230A C282V/I24L

L249M/I3L V218F/A31 S G245A/Q92C V36I/F230N C282V/I24V

L249M/I3M V218F/F93A G245A/Q92S V36I/ S87P C282V/D170S

G233D/G233Q V218F/L323C G245A/F230A V36I/ S87Q C282V/V229M

G233D/V159L V218F/L323V G245A/F230N V36I/L98H C282V/E360A

G233D/P129R V218F/T83G G245A/ S87P V36I/ S70K C282V/ S322V

G233D/G181A V218F/T83N G245A/ S87Q V36I/F351A C282V/F347I

G233D /G181 S V218F/Q92R G245A/L98H V36I/F351V C282V/V221F

G233D/E1 1 1P V218F/F267I G245A/ S70K V36I/M157Y C282V/V221I

G233D/E1 1 1 S V218F/F267Q G245A/F351A V36I/C44F C282V/G245S

G233D /F344Y V218F/E4K G245A/F351V V36I/C44Y C282V/Q92C

G233D/V165A V218F/E90D G245A/M157Y V36I/I3L C282V/Q92S

G233D /V218F V218F/T312K G245A/C44F V36I/I3M C282V/F230A

G233D/N96S V218F/T312N G245A/C44Y V36L/H131V C282V/F230N

G233D /F347Y V218F/L241V G245A/I3L V36L/H131Y C282V/ S87P

G233D/M206C V218F/V255I G245A/I3M V36L/ S243E C282V/ S87Q

G233D/M206L V218F/F344G G245C/C282E V36L/I21 1L C282V/L98H

G233D /P129V V218F/I76L G245C/C282I V36L/I21 1V C282V/ S70K

G233D/T65A V218F/I76M G245C/F335L V36L/I91F C282V/F351A

G233D /I106V V218F/G138K G245C/T248A V36L/E360G C282V/F351V

G233D /P186Q V218F/L238F G245C/T248D V36L/E360L C282V/M157Y

G233D/M319I V218F/L238T G245C/L284S V36L/A315R C282V/C44F

G233D/M319V V218F/I35L G245C/N350K V36L/A315S C282V/C44Y

G233D/G245A V218F/I35V G245C/N350R V36L/C282S C282V/I3L

G233D/G245C V218F/C208A G245C/F132L V36L/C282V C282V/I3M

G233D /C282E V218F/C208S G245C/I287L V36L/G135A G135A/V221C

G233D/C282I V218F/E240A G245C/V36I V36L/V221C G135A/V221M

G233D/F335L V218F/E240T G245C/V36L V36L/V221M G135A/R247M

G233D/T248A V218F/N148H G245C/H131V V36L/R247M G135A/R247N

G233D/T248D V218F/F94L G245C/H131Y V36L/R247N G135A/I91L

G233D/L284S V218F/F94Y G245C/ S243E V36L/I91L G135A/I91V

G233D/N350K V218F/V150L G245C/I21 1L V36L/I91V G135A/M160H Positions Positions Positions Positions Positions

G233D/N350R V218F/F68P G245C/I21 1V V36L/M160H G135A/L293F

G233D/F132L V218F/N148R G245C/I91F V36L/L293F G135A/L293S

G233D/I287L V218F/K361R G245C/E360G V36L/L293S G135A/L66F

G233D/V36I V218F/Q280E G245C/E360L V36L/L66F G135A/C282D

G233D/V36L V218F/Q280R G245C/A315R V36L/C282D G135A/A222H

G233D/H131V V218F/K225E G245C/A315S V36L/A222H G135A/A222L

G233D/H131Y V218F/K225G G245C/C282S V36L/A222L G135A/E356S

G233D/ S243E V218F/L238A G245C/C282V V36L/E356S G135A/ S109G

G233D/I21 1L V218F/L238S G245C/G135A V36L/ S 109G G135A/I290L

G233D /I21 1V V218F/C269A G245C/V221C V36L/I290L G135A/I290M

G233D/I91F V218F/C269I G245C/V221M V36L/I290M G135A/L330M

G233D/E360G V218F/D296P G245C/R247M V36L/L330M G135A/H131C

G233D/E360L V218F/F140Y G245C/R247N V36L/H131C G135A/A189G

G233D/A315R V218F/I24L G245C/I91L V36L/A189G G135A/Q193K

G233D /A315S V218F/I24V G245C/I91V V36L/Q193K G135A/Q193R

G233D/C282S V218F/D170S G245C/M160H V36L/Q193R G135A/L242I

G233D/C282V V218F/V229M G245C/L293F V36L/L242I G135A/Q108H

G233D/G135A V218F/E360A G245C/L293S V36L/Q108H G135A/F68V

G233D/V221C V218F/ S322V G245C/L66F V36L/F68V G135A/G100S

G233D/V221M V218F/F347I G245C/C282D V36L/G100S G135A/G100T

G233D/R247M V218F/V221F G245C/A222H V36L/G100T G135A/L323I

G233D/R247N V218F/V221I G245C/A222L V36L/L323I G135A/L323M

G233D /I91L V218F/G245S G245C/E356S V36L/L323M G135A/Q277D

G233D/I91V V218F/Q92C G245C/ S 109G V36L/Q277D G135A/Q277E

G233D/M160H V218F/Q92S G245C/I290L V36L/Q277E G135A/C269N

G233D/L293F V218F/F230A G245C/I290M V36L/C269N G135A/C269T

G233D/L293S V218F/F230N G245C/L330M V36L/C269T G135A/A326F

G233D /L66F V218F/ S87P G245C/H131C V36L/A326F G135A/A326I

G233D/C282D V218F/ S87Q G245C/A189G V36L/A326I G135A/L152F

G233D/A222H V218F/L98H G245C/Q193K V36L/L152F G135A/C282N

G233D/A222L V218F/ S70K G245C/Q193R V36L/C282N G135A/ S329P

G233D/E356S V218F/F351A G245C/L242I V36L/ S329P G135A/I45D

G233D / S109G V218F/F351V G245C/Q108H V36L/I45D G135A/I45L

G233D/I290L V218F/M157Y G245C/F68V V36L/I45L G135A/E258A

G233D/I290M V218F/C44F G245C/G100S V36L/E258A G135A/A272E

G233D/L330M V218F/C44Y G245C/G100T V36L/A272E G135A/T312A

G233D/H131C V218F/I3L G245C/L323I V36L/T312A G135A/T312R

G233D/A189G V218F/I3M G245C/L323M V36L/T312R G135A/M327Q

G233D/Q193K N96S /F347Y G245C/Q277D V36L/M327Q G135A/M327T

G233D/Q193R N96S /M206C G245C/Q277E V36L/M327T G135A/N174Y

G233D/L242I N96S /M206L G245C/C269N V36L/N174Y G135A/L340I

G233D/Q108H N96S /P129V G245C/C269T V36L/L340I G135A/L340M Positions Positions Positions Positions Positions

G233D/F68V N96S/T65A G245C/A326F V36L/L340M G135A/A189H

G233D/G100S N96S/I106V G245C/A326I V36L/A189H G135A/A189Y

G233D/G100T N96S/P186Q G245C/L152F V36L/A189Y G135A/N194R

G233D/L323I N96S/M319I G245C/C282N V36L/N194R G135A/N194S

G233D/L323M N96S/M319V G245C/S329P V36L/N194S G135A/L169V

G233D/Q277D N96S/G245A G245C/I45D V36L/L169V G135A/K225D

G233D/Q277E N96S/G245C G245C/I45L V36L/K225D G135A/K225S

G233D/C269N N96S/C282E G245C/E258A V36L/K225S G135A/A63I

G233D/C269T N96S/C282I G245C/A272E V36L/A63I G135A/A63P

G233D/A326F N96S/F335L G245C/T312A V36L/A63P G135A/I180L

G233D/A326I N96S/T248A G245C/T312R V36L/I180L G135A/I180V

G233D/L152F N96S/T248D G245C/M327Q V36L/I180V G135A/H151D

G233D/C282N N96S/L284S G245C/M327T V36L/H151D G135A/T220I

G233D/S329P N96S/N350K G245C/N174Y V36L/T220I G135A/T220S

G233D/I45D N96S/N350R G245C/L340I V36L/T220S G135A/L246I

G233D/I45L N96S/F132L G245C/L340M V36L/L246I G135A/A272P

G233D/E258A N96S/I287L G245C/A189H V36L/A272P G135A/S353E

G233D/A272E N96S/V36I G245C/A189Y V36L/S353E G135A/S353K

G233D/T312A N96S/V36L G245C/N194R V36L/S353K G135A/A256D

G233D/T312R N96S/H131V G245C/N194S V36L/A256D G135A/A256E

G233D/M327Q N96S/H131Y G245C/L169V V36L/A256E G135A/R224L

G233D/M327T N96S/S243E G245C/K225D V36L/R224L G135A/A134M

G233D/N174Y N96S/I211L G245C/K225S V36L/A134M G135A/V359E

G233D/L340I N96S/I211V G245C/A63I V36L/V359E G135A/V359K

G233D/L340M N96S/I91F G245C/A63P V36L/V359K G135A/S333A

G233D/A189H N96S/E360G G245C/I180L V36L/S333A G135A/S333E

G233D/A189Y N96S/E360L G245C/I180V V36L/S333E G135A/T352D

G233D/N194R N96S/A315R G245C/H151D V36L/T352D G135A/T352E

G233D/N194S N96S/A315S G245C/T220I V36L/T352E G135A/M157F

G233D/L169V N96S/C282S G245C/T220S V36L/M157F G135A/M157S

G233D/K225D N96S/C282V G245C/L246I V36L/M157S G135A/D14G

G233D/K225S N96S/G135A G245C/A272P V36L/D14G G135A/D296A

G233D/A63I N96S/V221C G245C/S353E V36L/D296A G135A/D296L

G233D/A63P N96S/V221M G245C/S353K V36L/D296L G135A/T314A

G233D/I180L N96S/R247M G245C/A256D V36L/T314A G135A/T314E

G233D/I180V N96S/R247N G245C/A256E V36L/T314E G135A/F267Y

G233D/H151D N96S/I91L G245C/R224L V36L/F267Y G135A/E71N

G233D/T220I N96S/I91V G245C/A134M V36L/E71N G135A/E252Q

G233D/T220S N96S/M160H G245C/V359E V36L/E252Q G135A/I367V

G233D/L246I N96S/L293F G245C/V359K V36L/I367V G135A/A31M

G233D/A272P N96S/L293S G245C/S333A V36L/A31M G135A/A31S

G233D/S353E N96S/L66F G245C/S333E V36L/A31S G135A/F93A Positions Positions Positions Positions Positions

G233D/S353K N96S/C282D G245C/T352D V36L/F93A G135A/L323C

G233D/A256D N96S/A222H G245C/T352E V36L/L323C G135A/L323V

G233D/A256E N96S/A222L G245C/M157F V36L/L323V G135A/T83G

G233D/R224L N96S/E356S G245C/M157S V36L/T83G G135A/T83N

G233D/A134M N96S/S109G G245C/D14G V36L/T83N G135A/Q92R

G233D/V359E N96S/I290L G245C/D296A V36L/Q92R G135A/F267I

G233D/V359K N96S/I290M G245C/D296L V36L/F267I G135A/F267Q

G233D/S333A N96S/L330M G245C/T314A V36L/F267Q G135A/E4K

G233D/S333E N96S/H131C G245C/T314E V36L/E4K G135A/E90D

G233D/T352D N96S/A189G G245C/F267Y V36L/E90D G135A/T312K

G233D/T352E N96S/Q193K G245C/E71N V36L/T312K G135A/T312N

G233D/M157F N96S/Q193R G245C/E252Q V36L/T312N G135A/L241V

G233D/M157S N96S/L242I G245C/I367V V36L/L241V G135A/V255I

G233D/D14G N96S/Q108H G245C/A31M V36L/V255I G135A/F344G

G233D/D296A N96S/F68V G245C/A31S V36L/F344G G135A/I76L

G233D/D296L N96S/G100S G245C/F93A V36L/I76L G135A/I76M

G233D/T314A N96S/G100T G245C/L323C V36L/I76M G135A/G138K

G233D/T314E N96S/L323I G245C/L323V V36L/G138K G135A/L238F

G233D/F267Y N96S/L323M G245C/T83G V36L/L238F G135A/L238T

G233D/E71N N96S/Q277D G245C/T83N V36L/L238T G135A/I35L

G233D/E252Q N96S/Q277E G245C/Q92R V36L/I35L G135A/I35V

G233D/I367V N96S/C269N G245C/F267I V36L/I35V G135A/C208A

G233D/A31M N96S/C269T G245C/F267Q V36L/C208A G135A/C208S

G233D/A31S N96S/A326F G245C/E4K V36L/C208S G135A/E240A

G233D/F93A N96S/A326I G245C/E90D V36L/E240A G135A/E240T

G233D/L323C N96S/L152F G245C/T312K V36L/E240T G135A/N148H

G233D/L323V N96S/C282N G245C/T312N V36L/N148H G135A/F94L

G233D/T83G N96S/S329P G245C/L241V V36L/F94L G135A/F94Y

G233D/T83N N96S/I45D G245C/V255I V36L/F94Y G135A/V150L

G233D/Q92R N96S/I45L G245C/F344G V36L/V150L G135A/F68P

G233D/F267I N96S/E258A G245C/I76L V36L/F68P G135A/N148R

G233D/F267Q N96S/A272E G245C/I76M V36L/N148R G135A/K361R

G233D/E4K N96S/T312A G245C/G138K V36L/K361R G135A/Q280E

G233D/E90D N96S/T312R G245C/L238F V36L/Q280E G135A/Q280R

G233D/T312K N96S/M327Q G245C/L238T V36L/Q280R G135A/K225E

G233D/T312N N96S/M327T G245C/I35L V36L/K225E G135A/K225G

G233D/L241V N96S/N174Y G245C/I35V V36L/K225G G135A/L238A

G233D/V255I N96S/L340I G245C/C208A V36L/L238A G135A/L238S

G233D/F344G N96S/L340M G245C/C208S V36L/L238S G135A/C269A

G233D/I76L N96S/A189H G245C/E240A V36L/C269A G135A/C269I

G233D/I76M N96S/A189Y G245C/E240T V36L/C269I G135A/D296P

G233D/G138K N96S/N194R G245C/N148H V36L/D296P G135A/F140Y Positions Positions Positions Positions Positions

G233D/L238F N96S/N194S G245C/F94L V36L/F140Y G135A/I24L

G233D/L238T N96S/L169V G245C/F94Y V36L/I24L G135A/I24V

G233D/I35L N96S/K225D G245C/V150L V36L/I24V G135A/D170S

G233D/I35V N96S/K225S G245C/F68P V36L/D170S G135A/V229M

G233D/C208A N96S/A63I G245C/N148R V36L/V229M G135A/E360A

G233D/C208S N96S/A63P G245C/K361R V36L/E360A G135A/S322V

G233D/E240A N96S/I180L G245C/Q280E V36L/S322V G135A/F347I

G233D/E240T N96S/I180V G245C/Q280R V36L/F347I G135A/V221F

G233D/N148H N96S/H151D G245C/K225E V36L/V221F G135A/V221I

G233D/F94L N96S/T220I G245C/K225G V36L/V221I G135A/G245S

G233D/F94Y N96S/T220S G245C/L238A V36L/G245S G135A/Q92C

G233D/V150L N96S/L246I G245C/L238S V36L/Q92C G135A/Q92S

G233D/F68P N96S/A272P G245C/C269A V36L/Q92S G135A/F230A

G233D/N148R N96S/S353E G245C/C269I V36L/F230A G135A/F230N

G233D/K361R N96S/S353K G245C/D296P V36L/F230N G135A/S87P

G233D/Q280E N96S/A256D G245C/F140Y V36L/S87P G135A/S87Q

G233D/Q280R N96S/A256E G245C/I24L V36L/S87Q G135A/L98H

G233D/K225E N96S/R224L G245C/I24V V36L/L98H G135A/S70K

G233D/K225G N96S/A134M G245C/D170S V36L/S70K G135A/F351A

G233D/L238A N96S/V359E G245C/V229M V36L/F351A G135A/F351V

G233D/L238S N96S/V359K G245C/E360A V36L/F351V G135A/M157Y

G233D/C269A N96S/S333A G245C/S322V V36L/M157Y G135A/C44F

G233D/C269I N96S/S333E G245C/F347I V36L/C44F G135A/C44Y

G233D/D296P N96S/T352D G245C/V221F V36L/C44Y G135A/I3L

G233D/F140Y N96S/T352E G245C/V221I V36L/I3L G135A/I3M

G233D/I24L N96S/M157F G245C/G245S V36L/I3M V221C/V221M

G233D/I24V N96S/M157S G245C/Q92C H131V/H131Y V221C/R247M

G233D/D170S N96S/D14G G245C/Q92S H131V/S243E V221C/R247N

G233D/V229M N96S/D296A G245C/F230A H131V/I211L V221C/I91L

G233D/E360A N96S/D296L G245C/F230N H131V/I211V V221C/I91V

G233D/S322V N96S/T314A G245C/S87P H131V/I91F V221C/M160H

G233D/F347I N96S/T314E G245C/S87Q H131V/E360G V221C/L293F

G233D/V221F N96S/F267Y G245C/L98H H131V/E360L V221C/L293S

G233D/V221I N96S/E71N G245C/S70K H131V/A315R V221C/L66F

G233D/G245S N96S/E252Q G245C/F351A H131V/A315S V221C/C282D

G233D/Q92C N96S/I367V G245C/F351V H131V/C282S V221C/A222H

G233D/Q92S N96S/A31M G245C/M157Y H131V/C282V V221C/A222L

G233D/F230A N96S/A31S G245C/C44F H131V/G135A V221C/E356S

G233D/F230N N96S/F93A G245C/C44Y H131V/V221C V221C/S109G

G233D/S87P N96S/L323C G245C/I3L H131V/V221M V221C/I290L

G233D/S87Q N96S/L323V G245C/I3M H131V/R247M V221C/I290M

G233D/L98H N96S/T83G C282E/C282I H131V/R247N V221C/L330M Positions Positions Positions Positions Positions

G233D/S70K N96S/T83N C282E/F335L H131V/I91L V221C/H131C

G233D/F351A N96S/Q92R C282E/T248A H131V/I91V V221C/A189G

G233D/F351V N96S/F267I C282E/T248D H131V/M160H V221C/Q193K

G233D/M157Y N96S/F267Q C282E/L284S H131V/L293F V221C/Q193R

G233D/C44F N96S/E4K C282E/N350K H131V/L293S V221C/L242I

G233D/C44Y N96S/E90D C282E/N350R H131V/L66F V221C/Q108H

G233D/I3L N96S/T312K C282E/F132L H131V/C282D V221C/F68V

G233D/I3M N96S/T312N C282E/I287L H131V/A222H V221C/G100S

G233Q/V159L N96S/L241V C282E/V36I H131V/A222L V221C/G100T

G233Q/P129R N96S/V255I C282E/V36L H131V/E356S V221C/L323I

G233Q/G181A N96S/F344G C282E/H131V H131V/S109G V221C/L323M

G233Q/G181S N96S/I76L C282E/H131Y H131V/I290L V221C/Q277D

G233Q/E111P N96S/I76M C282E/S243E H131V/I290M V221C/Q277E

G233Q/E111S N96S/G138K C282E/I211L H131V/L330M V221C/C269N

G233Q/F344Y N96S/L238F C282E/I211V H131V/H131C V221C/C269T

G233Q/V165A N96S/L238T C282E/I91F H131V/A189G V221C/A326F

G233Q/V218F N96S/I35L C282E/E360G H131V/Q193K V221C/A326I

G233Q/N96S N96S/I35V C282E/E360L H131V/Q193R V221C/L152F

G233Q/F347Y N96S/C208A C282E/A315R H131V/L242I V221C/C282N

G233Q/M206C N96S/C208S C282E/A315S H131V/Q108H V221C/S329P

G233Q/M206L N96S/E240A C282E/C282S H131V/F68V V221C/I45D

G233Q/P129V N96S/E240T C282E/C282V H131V/G100S V221C/I45L

G233Q/T65A N96S/N148H C282E/G135A H131V/G100T V221C/E258A

G233Q/I106V N96S/F94L C282E/V221C H131V/L323I V221C/A272E

G233Q/P186Q N96S/F94Y C282E/V221M H131V/L323M V221C/T312A

G233Q/M319I N96S/V150L C282E/R247M H131V/Q277D V221C/T312R

G233Q/M319V N96S/F68P C282E/R247N H131V/Q277E V221C/M327Q

G233Q/G245A N96S/N148R C282E/I91L H131V/C269N V221C/M327T

G233Q/G245C N96S/K361R C282E/I91V H131V/C269T V221C/N174Y

G233Q/C282E N96S/Q280E C282E/M160H H131V/A326F V221C/L340I

G233Q/C282I N96S/Q280R C282E/L293F H131V/A326I V221C/L340M

G233Q/F335L N96S/K225E C282E/L293S H131V/L152F V221C/A189H

G233Q/T248A N96S/K225G C282E/L66F H131V/C282N V221C/A189Y

G233Q/T248D N96S/L238A C282E/C282D H131V/S329P V221C/N194R

G233Q/L284S N96S/L238S C282E/A222H H131V/I45D V221C/N194S

G233Q/N350K N96S/C269A C282E/A222L H131V/I45L V221C/L169V

G233Q/N350R N96S/C269I C282E/E356S H131V/E258A V221C/K225D

G233Q/F132L N96S/D296P C282E/S109G H131V/A272E V221C/K225S

G233Q/I287L N96S/F140Y C282E/I290L H131V/T312A V221C/A63I

G233Q/V36I N96S/I24L C282E/I290M H131V/T312R V221C/A63P

G233Q/V36L N96S/I24V C282E/L330M H131V/M327Q V221C/I180L

G233Q/H131V N96S/D170S C282E/H131C H131V/M327T V221C/I180V Positions Positions Positions Positions Positions

G233Q/H131Y N96S /V229M C282E/A189G H131V/N174Y V221C/H151D

G233Q/ S243E N96S /E360A C282E/Q193K H131V/L340I V221C/T220I

G233Q/I21 1L N96S / S322V C282E/Q193R H131V/L340M V221C/T220S

G233Q /I21 1V N96S /F347I C282E/L242I H131V/A189H V221C/L246I

G233Q/I91F N96S /V221F C282E/Q108H H131V/A189Y V221C/A272P

G233Q/E360G N96S /V221I C282E/F68V H131V/N194R V221C/ S353E

G233Q/E360L N96S /G245S C282E/G100S H131V/N194S V221C/ S353K

G233Q/A315R N96S /Q92C C282E/G100T H131V/L169V V221C/A256D

G233Q /A315S N96S /Q92S C282E/L323I H131V/K225D V221C/A256E

G233Q/C282S N96S /F230A C282E/L323M H131V/K225S V221C/R224L

G233Q/C282V N96S /F230N C282E/Q277D H131V/A63I V221C/A134M

G233Q/G135A N96S / S87P C282E/Q277E H131V/A63P V221C/V359E

G233Q/V221C N96S / S87Q C282E/C269N H131V/I180L V221C/V359K

G233Q/V221M N96S /L98H C282E/C269T H131V/I180V V221C/ S333A

G233Q/R247M N96S / S70K C282E/A326F H131V/H151D V221C/ S333E

G233Q/R247N N96S /F351A C282E/A326I H131V/T220I V221C/T352D

G233Q /I91L N96S /F351V C282E/L152F H131V/T220S V221C/T352E

G233Q/I91V N96S/M157Y C282E/C282N H131V/L246I V221C/M157F

G233Q/M160H N96S /C44F C282E/ S329P H131V/A272P V221C/M157S

G233Q/L293F N96S /C44Y C282E/I45D H131V/ S353E V221C/D14G

G233Q/L293S N96S /I3L C282E/I45L H131V/ S353K V221C/D296A

G233Q /L66F N96S /I3M C282E/E258A H131V/A256D V221C/D296L

G233Q/C282D F347Y/M206C C282E/A272E H131V/A256E V221C/T314A

G233Q/A222H F347Y/M206L C282E/T312A H131V/R224L V221C/T314E

G233Q/A222L F347Y/P129V C282E/T312R H131V/A134M V221C/F267Y

G233Q/E356S F347Y/T65A C282E/M327Q H131V/V359E V221C/E71N

G233Q / S109G F347Y/I106V C282E/M327T H131V/V359K V221C/E252Q

G233Q/I290L F347Y/P186Q C282E/N174Y H131V/ S333A V221C/I367V

G233Q/I290M F347Y/M319I C282E/L340I H131V/ S333E V221C/A31M

G233Q/L330M F347Y/M319V C282E/L340M H131V/T352D V221C/A31 S

G233Q/H131C F347Y/G245A C282E/A189H H131V/T352E V221C/F93A

G233Q/A189G F347Y/G245C C282E/A189Y H131V/M157F V221C/L323C

G233Q/Q193K F347Y/C282E C282E/N194R H131V/M157S V221C/L323V

G233Q/Q193R F347Y/C282I C282E/N194S H131V/D14G V221C/T83G

G233Q/L242I F347Y/F335L C282E/L169V H131V/D296A V221C/T83N

G233Q/Q108H F347Y/T248A C282E/K225D H131V/D296L V221C/Q92R

G233Q/F68V F347Y/T248D C282E/K225S H131V/T314A V221C/F267I

G233Q /G100S F347Y/L284S C282E/A63I H131V/T314E V221C/F267Q

G233Q/G100T F347Y/N350K C282E/A63P H131V/F267Y V221C/E4K

G233Q/L323I F347Y/N350R C282E/I180L H131V/E71N V221C/E90D

G233Q/L323M F347Y/F132L C282E/I180V H131V/E252Q V221C/T312K

G233Q/Q277D F347Y/I287L C282E/H151D H131V/I367V V221C/T312N Positions Positions Positions Positions Positions

G233Q/Q277E F347Y/V36I C282E/T220I H131V/A31M V221C/L241V

G233Q/C269N F347Y/V36L C282E/T220S H131V/A31 S V221C/V255I

G233Q /C269T F347Y/H131V C282E/L246I H131V/F93A V221C/F344G

G233Q /A326F F347Y/H131Y C282E/A272P H131V/L323C V221C/I76L

G233Q /A326I F347Y/ S243E C282E/ S353E H131V/L323V V221C/I76M

G233Q/L152F F347Y/I21 1L C282E/ S353K H131V/T83G V221C/G138K

G233Q/C282N F347Y/I21 1V C282E/A256D H131V/T83N V221C/L238F

G233Q/ S329P F347Y/I91F C282E/A256E H131V/Q92R V221C/L238T

G233Q/I45D F347Y/E360G C282E/R224L H131V/F267I V221C/I35L

G233Q /I45L F347Y/E360L C282E/A134M H131V/F267Q V221C/I35V

G233Q/E258A F347Y/A315R C282E/V359E H131V/E4K V221C/C208A

G233Q/A272E F347Y/A315S C282E/V359K H131V/E90D V221C/C208S

G233Q/T312A F347Y/C282S C282E/ S333A H131V/T312K V221C/E240A

G233Q /T312R F347Y/C282V C282E/ S333E H131V/T312N V221C/E240T

G233Q/M327Q F347Y/G135A C282E/T352D H131V/L241V V221C/N148H

G233Q/M327T F347Y/V221C C282E/T352E H131V/V255I V221C/F94L

G233Q/N174Y F347Y/V221M C282E/M157F H131V/F344G V221C/F94Y

G233Q/L340I F347Y/R247M C282E/M157S H131V/I76L V221C/V150L

G233Q/L340M F347Y/R247N C282E/D14G H131V/I76M V221C/F68P

G233Q/A189H F347Y/I91L C282E/D296A H131V/G138K V221C/N148R

G233Q/A189Y F347Y/I91V C282E/D296L H131V/L238F V221C/K361R

G233Q/N194R F347Y/M160H C282E/T314A H131V/L238T V221C/Q280E

G233Q /N194S F347Y/L293F C282E/T314E H131V/I35L V221C/Q280R

G233Q/L169V F347Y/L293S C282E/F267Y H131V/I35V V221C/K225E

G233Q/K225D F347Y/L66F C282E/E71N H131V/C208A V221C/K225G

G233Q /K225S F347Y/C282D C282E/E252Q H131V/C208S V221C/L238A

G233Q/A63I F347Y/A222H C282E/I367V H131V/E240A V221C/L238S

G233Q/A63P F347Y/A222L C282E/A31M H131V/E240T V221C/C269A

G233Q/I180L F347Y/E356S C282E/A31 S H131V/N148H V221C/C269I

G233Q /I180V F347Y/ S109G C282E/F93A H131V/F94L V221C/D296P

G233Q/H151D F347Y/I290L C282E/L323C H131V/F94Y V221C/F140Y

G233Q/T220I F347Y/I290M C282E/L323V H131V/V150L V221C/I24L

G233Q/T220S F347Y/L330M C282E/T83G H131V/F68P V221C/I24V

G233Q/L246I F347Y/H131C C282E/T83N H131V/N148R V221C/D170S

G233Q /A272P F347Y/A189G C282E/Q92R H131V/K361R V221C/V229M

G233Q/ S353E F347Y/Q193K C282E/F267I H131V/Q280E V221C/E360A

G233Q / S353K F347Y/Q193R C282E/F267Q H131V/Q280R V221C/ S322V

G233Q/A256D F347Y/L242I C282E/E4K H131V/K225E V221C/F347I

G233Q/A256E F347Y/Q108H C282E/E90D H131V/K225G V221C/V221F

G233Q /R224L F347Y/F68V C282E/T312K H131V/L238A V221C/V221I

G233Q/A134M F347Y/G100S C282E/T312N H131V/L238S V221C/G245S

G233Q/V359E F347Y/G100T C282E/L241V H131V/C269A V221C/Q92C Positions Positions Positions Positions Positions

G233Q/V359K F347Y/L323I C282E/V255I H131V/C269I V221C/Q92S

G233Q / S333A F347Y/L323M C282E/F344G H131V/D296P V221C/F230A

G233Q/ S333E F347Y/Q277D C282E/I76L H131V/F140Y V221C/F230N

G233Q/T352D F347Y/Q277E C282E/I76M H131V/I24L V221C/ S87P

G233Q/T352E F347Y/C269N C282E/G138K H131V/I24V V221C/ S87Q

G233Q /M157F F347Y/C269T C282E/L238F H131V/D170S V221C/L98H

G233Q /M157S F347Y/A326F C282E/L238T H131V/V229M V221C/ S70K

G233Q/D14G F347Y/A326I C282E/I35L H131V/E360A V221C/F351A

G233Q/D296A F347Y/L152F C282E/I35V H131V/ S322V V221C/F351V

G233Q/D296L F347Y/C282N C282E/C208A H131V/F347I V221C/M157Y

G233Q/T314A F347Y/ S329P C282E/C208S H131V/V221F V221C/C44F

G233Q/T314E F347Y/I45D C282E/E240A H131V/V221I V221C/C44Y

G233Q /F267Y F347Y/I45L C282E/E240T H131V/G245S V221C/I3L

G233Q/E71N F347Y/E258A C282E/N148H H131V/Q92C V221C/I3M

G233Q/E252Q F347Y/A272E C282E/F94L H131V/Q92S V221M/R247M

G233Q /I367V F347Y/T312A C282E/F94Y H131V/F230A V221M/R247N

G233Q/A31M F347Y/T312R C282E/V150L H131V/F230N V221M/I91L

G233Q/A31 S F347Y/M327Q C282E/F68P H131V/ S87P V221M/I91V

G233Q/F93A F347Y/M327T C282E/N148R H131V/ S87Q V221M/M160H

G233Q /L323C F347Y/N174Y C282E/K361R H131V/L98H V221M/L293F

G233Q/L323V F347Y/L340I C282E/Q280E H131V/ S70K V221M/L293S

G233Q/T83G F347Y/L340M C282E/Q280R H131V/F351A V221M/L66F

G233Q/T83N F347Y/A189H C282E/K225E H131V/F351V V221M/C282D

G233Q /Q92R F347Y/A189Y C282E/K225G H131V/M157Y V221M/A222H

G233Q/F267I F347Y/N194R C282E/L238A H131V/C44F V221M/A222L

G233Q /F267Q F347Y/N194S C282E/L238S H131V/C44Y V221M/E356S

G233Q/E4K F347Y/L169V C282E/C269A H131V/I3L V221M/ S109G

G233Q/E90D F347Y/K225D C282E/C269I H131V/I3M V221M/I290L

G233Q/T312K F347Y/K225S C282E/D296P H131Y/ S243E V221M/I290M

G233Q/T312N F347Y/A63I C282E/F140Y H131Y/I21 1L V221M/L330M

G233Q/L241V F347Y/A63P C282E/I24L H131Y/I21 1V V221M/H131C

G233Q /V255I F347Y/I180L C282E/I24V H131Y/I91F V221M/A189G

G233Q /F344G F347Y/I180V C282E/D170S H131Y/E360G V221M/Q193K

G233Q /I76L F347Y/H151D C282E/V229M H131Y/E360L V221M/Q193R

G233Q/I76M F347Y/T220I C282E/E360A H131Y/A315R V221M/L242I

G233Q/G138K F347Y/T220S C282E/ S322V H131Y/A315S V221M/Q108H

G233Q/L238F F347Y/L246I C282E/F347I H131Y/C282S V221M/F68V

G233Q/L238T F347Y/A272P C282E/V221F H131Y/C282V V221M/G100S

G233Q /I35L F347Y/ S353E C282E/V221I H131Y/G135A V221M/G100T

G233Q/I35V F347Y/ S353K C282E/G245S H131Y/V221C V221M/L323I

G233Q/C208A F347Y/A256D C282E/Q92C H131Y/V221M V221M/L323M

G233Q/C208S F347Y/A256E C282E/Q92S H131Y/R247M V221M/Q277D Positions Positions Positions Positions Positions

G233Q/E240A F347Y/R224L C282E/F230A H131Y/R247N V221M/Q277E

G233Q/E240T F347Y/A134M C282E/F230N H131Y/I91L V221M/C269N

G233Q/N148H F347Y/V359E C282E/ S87P H131Y/I91V V221M/C269T

G233Q /F94L F347Y/V359K C282E/ S87Q H131Y/M160H V221M/A326F

G233Q/F94Y F347Y/ S333A C282E/L98H H131Y/L293F V221M/A326I

G233Q/V150L F347Y/ S333E C282E/ S70K H131Y/L293S V221M/L152F

G233Q/F68P F347Y/T352D C282E/F351A H131Y/L66F V221M/C282N

G233Q/N148R F347Y/T352E C282E/F351V H131Y/C282D V221M/ S329P

G233Q/K361R F347Y/M157F C282E/M157Y H131Y/A222H V221M/I45D

G233Q/Q280E F347Y/M157S C282E/C44F H131Y/A222L V221M/I45L

G233Q/Q280R F347Y/D14G C282E/C44Y H131Y/E356S V221M/E258A

G233Q/K225E F347Y/D296A C282E/I3L H131Y/ S 109G V221M/A272E

G233Q/K225G F347Y/D296L C282E/I3M H131Y/I290L V221M/T312A

G233Q/L238A F347Y/T314A C282I/F335L H131Y/I290M V221M/T312R

G233Q/L238S F347Y/T314E C282I/T248A H131Y/L330M V221M/M327Q

G233Q/C269A F347Y/F267Y C282I/T248D H131Y/H131C V221M/M327T

G233Q/C269I F347Y/E71N C282I/L284S H131Y/A189G V221M/N174Y

G233Q /D296P F347Y/E252Q C282I/N350K H131Y/Q193K V221M/L340I

G233Q /F140Y F347Y/I367V C282I/N350R H131Y/Q193R V221M/L340M

G233Q /I24L F347Y/A31M C282I/F132L H131Y/L242I V221M/A189H

G233Q/I24V F347Y/A31 S C282I/I287L H131Y/Q108H V221M/A189Y

G233Q /D170S F347Y/F93A C282I/V36I H131Y/F68V V221M/N194R

G233Q/V229M F347Y/L323C C282I/V36L H131Y/G100S V221M/N194S

G233Q/E360A F347Y/L323V C282I/H131V H131Y/G100T V221M/L169V

G233Q / S322V F347Y/T83G C282I/H131Y H131Y/L323I V221M/K225D

G233Q/F347I F347Y/T83N C282I/ S243E H131Y/L323M V221M/K225S

G233Q /V221F F347Y/Q92R C282I/I21 1L H131Y/Q277D V221M/A63I

G233Q /V221I F347Y/F267I C282I/I211V H131Y/Q277E V221M/A63P

G233Q /G245S F347Y/F267Q C282I/I91F H131Y/C269N V221M/I180L

G233Q /Q92C F347Y/E4K C282I/E360G H131Y/C269T V221M/I180V

G233Q/Q92S F347Y/E90D C282I/E360L H131Y/A326F V221M/H151D

G233Q /F230A F347Y/T312K C282I/A315R H131Y/A326I V221M/T220I

G233Q /F230N F347Y/T312N C282I/A315S H131Y/L152F V221M/T220S

G233Q/ S87P F347Y/L241V C282I/C282S H131Y/C282N V221M/L246I

G233Q/ S87Q F347Y/V255I C282I/C282V H131Y/ S329P V221M/A272P

G233Q/L98H F347Y/F344G C282I/G135A H131Y/I45D V221M/ S353E

G233Q/ S70K F347Y/I76L C282I/V221C H131Y/I45L V221M/ S353K

G233Q /F351A F347Y/I76M C282I/V221M H131Y/E258A V221M/A256D

G233Q /F351V F347Y/G138K C282I/R247M H131Y/A272E V221M/A256E

G233Q/M157Y F347Y/L238F C282I/R247N H131Y/T312A V221M/R224L

G233Q/C44F F347Y/L238T C282I/I91L H131Y/T312R V221M/A134M

G233Q /C44Y F347Y/I35L C282I/I91V H131Y/M327Q V221M/V359E Positions Positions Positions Positions Positions

G233Q/I3L F347Y/I35V C282I/M160H H131Y/M327T V221M/V359K

G233Q/I3M F347Y/C208A C282I/L293F H131Y/N174Y V221M/ S333A

V159L/P129R F347Y/C208S C282I/L293S H131Y/L340I V221M/ S333E

V159L/G181A F347Y/E240A C282I/L66F H131Y/L340M V221M/T352D

V159L/G181 S F347Y/E240T C282I/C282D H131Y/A189H V221M/T352E

V159L/E1 11P F347Y/N148H C282I/A222H H131Y/A189Y V221M/M157F

V159L/E1 11 S F347Y/F94L C282I/A222L H131Y/N194R V221M/M157S

V159L/F344Y F347Y/F94Y C282I/E356S H131Y/N194S V221M/D14G

V159L/V165A F347Y/V150L C282I/ S 109G H131Y/L169V V221M/D296A

V159L/V218F F347Y/F68P C282I/I290L H131Y/K225D V221M/D296L

V159L/N96S F347Y/N148R C282I/I290M H131Y/K225S V221M/T314A

V159L/F347Y F347Y/K361R C282I/L330M H131Y/A63I V221M/T314E

V159L/M206C F347Y/Q280E C282I/H131C H131Y/A63P V221M/F267Y

V159L/M206L F347Y/Q280R C282I/A189G H131Y/I180L V221M/E71N

V159L/P129V F347Y/K225E C282I/Q193K H131Y/I180V V221M/E252Q

V159L/T65A F347Y/K225G C282I/Q193R H131Y/H151D V221M/I367V

V159L/I106V F347Y/L238A C282I/L242I H131Y/T220I V221M/A31M

V159L/P186Q F347Y/L238S C282I/Q108H H131Y/T220S V221M/A31 S

V159L/M319I F347Y/C269A C282I/F68V H131Y/L246I V221M/F93A

V159L/M319V F347Y/C269I C282I/G100S H131Y/A272P V221M/L323C

V159L/G245A F347Y/D296P C282I/G100T H131Y/ S353E V221M/L323V

V159L/G245C F347Y/F140Y C282I/L323I H131Y/ S353K V221M/T83G

V159L/C282E F347Y/I24L C282I/L323M H131Y/A256D V221M/T83N

V159L/C282I F347Y/I24V C282I/Q277D H131Y/A256E V221M/Q92R

V159L/F335L F347Y/D170S C282I/Q277E H131Y/R224L V221M/F267I

V159L/T248A F347Y/V229M C282I/C269N H131Y/A134M V221M/F267Q

V159L/T248D F347Y/E360A C282I/C269T H131Y/V359E V221M/E4K

V159L/L284S F347Y/ S322V C282I/A326F H131Y/V359K V221M/E90D

V159L/N350K F347Y/F347I C282I/A326I H131Y/ S333A V221M/T312K

V159L/N350R F347Y/V221F C282I/L152F H131Y/ S333E V221M/T312N

V159L/F132L F347Y/V221I C282I/C282N H131Y/T352D V221M/L241V

V159L/I287L F347Y/G245S C282I/ S329P H131Y/T352E V221M/V255I

V159L/V36I F347Y/Q92C C282I/I45D H131Y/M157F V221M/F344G

V159L/V36L F347Y/Q92S C282I/I45L H131Y/M157S V221M/I76L

V159L/H131V F347Y/F230A C282I/E258A H131Y/D14G V221M/I76M

V159L/H131Y F347Y/F230N C282I/A272E H131Y/D296A V221M/G138K

V159L/ S243E F347Y/ S87P C282I/T312A H131Y/D296L V221M/L238F

V159L/I21 1L F347Y/ S87Q C282I/T312R H131Y/T314A V221M/L238T

V159L/I211V F347Y/L98H C282I/M327Q H131Y/T314E V221M/I35L

V159L/I91F F347Y/ S70K C282I/M327T H131Y/F267Y V221M/I35V

V159L/E360G F347Y/F351A C282I/N174Y H131Y/E71N V221M/C208A

V159L/E360L F347Y/F351V C282I/L340I H131Y/E252Q V221M/C208S Positions Positions Positions Positions Positions

V159L/A315R F347Y/M157Y C282I/L340M H131Y/I367V V221M/E240A

V159L/A315S F347Y/C44F C282I/A189H H131Y/A31M V221M/E240T

V159L/C282S F347Y/C44Y C282I/A189Y H131Y/A31 S V221M/N148H

V159L/C282V F347Y/I3L C282I/N194R H131Y/F93A V221M/F94L

V159L/G135A F347Y/I3M C282I/N194S H131Y/L323C V221M/F94Y

V159L/V221C M206C/M206L C282I/L169V H131Y/L323V V221M/V150L

V159L/V221M M206C/P129V C282I/K225D H131Y/T83G V221M/F68P

V159L/R247M M206C/T65A C282I/K225S H131Y/T83N V221M/N148R

V159L/R247N M206C/I106V C282I/A63I H131Y/Q92R V221M/K361R

V159L/I91L M206C/P186Q C282I/A63P H131Y/F267I V221M/Q280E

V159L/I91V M206C/M319I C282I/I180L H131Y/F267Q V221M/Q280R

V159L/M160H M206C/M319V C282I/I180V H131Y/E4K V221M/K225E

V159L/L293F M206C/G245A C282I/H151D H131Y/E90D V221M/K225G

V159L/L293S M206C/G245C C282I/T220I H131Y/T312K V221M/L238A

V159L/L66F M206C/C282E C282I/T220S H131Y/T312N V221M/L238S

V159L/C282D M206C/C282I C282I/L246I H131Y/L241V V221M/C269A

V159L/A222H M206C/F335L C282I/A272P H131Y/V255I V221M/C269I

V159L/A222L M206C/T248A C282I/ S353E H131Y/F344G V221M/D296P

V159L/E356S M206C/T248D C282I/ S353K H131Y/I76L V221M/F140Y

V159L/ S 109G M206C/L284S C282I/A256D H131Y/I76M V221M/I24L

V159L/I290L M206C/N350K C282I/A256E H131Y/G138K V221M/I24V

V159L/I290M M206C/N350R C282I/R224L H131Y/L238F V221M/D170S

V159L/L330M M206C/F132L C282I/A134M H131Y/L238T V221M/V229M

V159L/H131C M206C/I287L C282I/V359E H131Y/I35L V221M/E360A

V159L/A189G M206C/V36I C282I/V359K H131Y/I35V V221M/ S322V

V159L/Q193K M206C/V36L C282I/ S333A H131Y/C208A V221M/F347I

V159L/Q193R M206C/H131V C282I/ S333E H131Y/C208S V221M/V221F

V159L/L242I M206C/H131Y C282I/T352D H131Y/E240A V221M/V221I

V159L/Q108H M206C/ S243E C282I/T352E H131Y/E240T V221M/G245S

V159L/F68V M206C/I21 1L C282I/M157F H131Y/N148H V221M/Q92C

V159L/G100S M206C/I21 1V C282I/M157S H131Y/F94L V221M/Q92S

V159L/G100T M206C/I91F C282I/D14G H131Y/F94Y V221M/F230A

V159L/L323I M206C/E360G C282I/D296A H131Y/V150L V221M/F230N

V159L/L323M M206C/E360L C282I/D296L H131Y/F68P V221M/ S87P

V159L/Q277D M206C/A315R C282I/T314A H131Y/N148R V221M/ S87Q

V159L/Q277E M206C/A315S C282I/T314E H131Y/K361R V221M/L98H

V159L/C269N M206C/C282S C282I/F267Y H131Y/Q280E V221M/ S70K

V159L/C269T M206C/C282V C282I/E71N H131Y/Q280R V221M/F351A

V159L/A326F M206C/G135A C282I/E252Q H131Y/K225E V221M/F351V

V159L/A326I M206C/V221C C282I/I367V H131Y/K225G V221M/M157Y

V159L/L152F M206C/V221M C282I/A31M H131Y/L238A V221M/C44F

V159L/C282N M206C/R247M C282I/A31 S H131Y/L238S V221M/C44Y Positions Positions Positions Positions Positions

V159L/ S329P M206C/R247N C282I/F93A H131Y/C269A V221M/I3L

V159L/I45D M206C/I91L C282I/L323C H131Y/C269I V221M/I3M

V159L/I45L M206C/I91V C282I/L323V H131Y/D296P R247M/R247N

V159L/E258A M206C/M160H C282I/T83G H131Y/F140Y R247M/I91L

V159L/A272E M206C/L293F C282I/T83N H131Y/I24L R247M/I91V

V159L/T312A M206C/L293S C282I/Q92R H131Y/I24V R247M/M160H

V159L/T312R M206C/L66F C282I/F267I H131Y/D170S R247M/L293F

V159L/M327Q M206C/C282D C282I/F267Q H131Y/V229M R247M/L293S

V159L/M327T M206C/A222H C282I/E4K H131Y/E360A R247M/L66F

V159L/N174Y M206C/A222L C282I/E90D H131Y/ S322V R247M/C282D

V159L/L340I M206C/E356S C282I/T312K H131Y/F347I R247M/A222H

V159L/L340M M206C/ S109G C282I/T312N H131Y/V221F R247M/A222L

V159L/A189H M206C/I290L C282I/L241V H131Y/V221I R247M/E356S

V159L/A189Y M206C/I290M C282I/V255I H131Y/G245S R247M/ S109G

V159L/N194R M206C/L330M C282I/F344G H131Y/Q92C R247M/I290L

V159L/N194S M206C/H131C C282I/I76L H131Y/Q92S R247M/I290M

V159L/L169V M206C/A189G C282I/I76M H131Y/F230A R247M/L330M

V159L/K225D M206C/Q193K C282I/G138K H131Y/F230N R247M/H131C

V159L/K225S M206C/Q193R C282I/L238F H131Y/ S87P R247M/A189G

V159L/A63I M206C/L242I C282I/L238T H131Y/ S87Q R247M/Q193K

V159L/A63P M206C/Q108H C282I/I35L H131Y/L98H R247M/Q193R

V159L/I180L M206C/F68V C282I/I35V H131Y/ S70K R247M/L242I

V159L/I180V M206C/G100S C282I/C208A H131Y/F351A R247M/Q108H

V159L/H151D M206C/G100T C282I/C208S H131Y/F351V R247M/F68V

V159L/T220I M206C/L323I C282I/E240A H131Y/M157Y R247M/G100S

V159L/T220S M206C/L323M C282I/E240T H131Y/C44F R247M/G100T

V159L/L246I M206C/Q277D C282I/N148H H131Y/C44Y R247M/L323I

V159L/A272P M206C/Q277E C282I/F94L H131Y/I3L R247M/L323M

V159L/ S353E M206C/C269N C282I/F94Y H131Y/I3M R247M/Q277D

V159L/ S353K M206C/C269T C282I/V150L S243E/I21 1L R247M/Q277E

V159L/A256D M206C/A326F C282I/F68P S243E/I21 1V R247M/C269N

V159L/A256E M206C/A326I C282I/N148R S243E/I91F R247M/C269T

V159L/R224L M206C/L152F C282I/K361R S243E/E360G R247M/A326F

V159L/A134M M206C/C282N C282I/Q280E S243E/E360L R247M/A326I

V159L/V359E M206C/ S329P C282I/Q280R S243E/A315R R247M/L152F

V159L/V359K M206C/I45D C282I/K225E S243E/A315S R247M/C282N

V159L/ S333A M206C/I45L C282I/K225G S243E/C282S R247M/ S329P

V159L/ S333E M206C/E258A C282I/L238A S243E/C282V R247M/I45D

V159L/T352D M206C/A272E C282I/L238S S243E/G135A R247M/I45L

V159L/T352E M206C/T312A C282I/C269A S243E/V221C R247M/E258A

V159L/M157F M206C/T312R C282I/C269I S243E/V221M R247M/A272E

V159L/M157S M206C/M327Q C282I/D296P S243E/R247M R247M/T312A Positions Positions Positions Positions Positions

V159L/D14G M206C/M327T C282I/F140Y S243E/R247N R247M/T312R

V159L/D296A M206C/N174Y C282I/I24L S243E/I91L R247M/M327Q

V159L/D296L M206C/L340I C282I/I24V S243E/I91V R247M/M327T

V159L/T314A M206C/L340M C282I/D170S S243E/M160H R247M/N174Y

V159L/T314E M206C/A189H C282I/V229M S243E/L293F R247M/L340I

V159L/F267Y M206C/A189Y C282I/E360A S243E/L293S R247M/L340M

V159L/E71N M206C/N194R C282I/ S322V S243E/L66F R247M/A189H

V159L/E252Q M206C/N194S C282I/F347I S243E/C282D R247M/A189Y

V159L/I367V M206C/L169V C282I/V221F S243E/A222H R247M/N194R

V159L/A31M M206C/K225D C282I/V221I S243E/A222L R247M/N194S

V159L/A31S M206C/K225S C282I/G245S S243E/E356S R247M/L169V

V159L/F93A M206C/A63I C282I/Q92C S243E/ S109G R247M/K225D

V159L/L323C M206C/A63P C282I/Q92S S243E/I290L R247M/K225S

V159L/L323V M206C/I180L C282I/F230A S243E/I290M R247M/A63I

V159L/T83G M206C/I180V C282I/F230N S243E/L330M R247M/A63P

V159L/T83N M206C/H151D C282I/ S87P S243E/H131C R247M/I180L

V159L/Q92R M206C/T220I C282I/ S87Q S243E/A189G R247M/I180V

V159L/F267I M206C/T220S C282I/L98H S243E/Q193K R247M/H151D

V159L/F267Q M206C/L246I C282I/ S70K S243E/Q193R R247M/T220I

V159L/E4K M206C/A272P C282I/F351A S243E/L242I R247M/T220S

V159L/E90D M206C/ S353E C282I/F351V S243E/Q108H R247M/L246I

V159L/T312K M206C/ S353K C282I/M157Y S243E/F68V R247M/A272P

V159L/T312N M206C/A256D C282I/C44F S243E/G100S R247M/ S353E

V159L/L241V M206C/A256E C282I/C44Y S243E/G100T R247M/ S353K

V159L/V255I M206C/R224L C282I/I3L S243E/L323I R247M/A256D

V159L/F344G M206C/A134M C282I/I3M S243E/L323M R247M/A256E

V159L/I76L M206C/V359E F335L/T248A S243E/Q277D R247M/R224L

V159L/I76M M206C/V359K F335L/T248D S243E/Q277E R247M/A134M

V159L/G138K M206C/ S333A F335L/L284S S243E/C269N R247M/V359E

V159L/L238F M206C/ S333E F335L/N350K S243E/C269T R247M/V359K

V159L/L238T M206C/T352D F335L/N350R S243E/A326F R247M/ S333A

V159L/I35L M206C/T352E F335L/F132L S243E/A326I R247M/ S333E

V159L/I35V M206C/M157F F335L/I287L S243E/L152F R247M/T352D

V159L/C208A M206C/M157S F335L/V36I S243E/C282N R247M/T352E

V159L/C208S M206C/D14G F335L/V36L S243E/ S329P R247M/M157F

V159L/E240A M206C/D296A F335L/H131V S243E/I45D R247M/M157S

V159L/E240T M206C/D296L F335L/H131Y S243E/I45L R247M/D14G

V159L/N148H M206C/T314A F335L/ S243E S243E/E258A R247M/D296A

V159L/F94L M206C/T314E F335L/I21 1L S243E/A272E R247M/D296L

V159L/F94Y M206C/F267Y F335L/I21 1V S243E/T312A R247M/T314A

V159L/V150L M206C/E71N F335L/I91F S243E/T312R R247M/T314E

V159L/F68P M206C/E252Q F335L/E360G S243E/M327Q R247M/F267Y Positions Positions Positions Positions Positions

V159L/N148R M206C/I367V F335L/E360L S243E/M327T R247M/E71N

V159L/K361R M206C/A31M F335L/A315R S243E/N174Y R247M/E252Q

V159L/Q280E M206C/A31 S F335L/A315S S243E/L340I R247M/I367V

V159L/Q280R M206C/F93A F335L/C282S S243E/L340M R247M/A31M

V159L/K225E M206C/L323C F335L/C282V S243E/A189H R247M/A31S

V159L/K225G M206C/L323V F335L/G135A S243E/A189Y R247M/F93A

V159L/L238A M206C/T83G F335L/V221C S243E/N194R R247M/L323C

V159L/L238S M206C/T83N F335L/V221M S243E/N194S R247M/L323V

V159L/C269A M206C/Q92R F335L/R247M S243E/L169V R247M/T83G

V159L/C269I M206C/F267I F335L/R247N S243E/K225D R247M/T83N

V159L/D296P M206C/F267Q F335L/I91L S243E/K225S R247M/Q92R

V159L/F140Y M206C/E4K F335L/I91V S243E/A63I R247M/F267I

V159L/I24L M206C/E90D F335L/M160H S243E/A63P R247M/F267Q

V159L/I24V M206C/T312K F335L/L293F S243E/I180L R247M/E4K

V159L/D170S M206C/T312N F335L/L293S S243E/I180V R247M/E90D

V159L/V229M M206C/L241V F335L/L66F S243E/H151D R247M/T312K

V159L/E360A M206C/V255I F335L/C282D S243E/T220I R247M/T312N

V159L/ S322V M206C/F344G F335L/A222H S243E/T220S R247M/L241V

V159L/F347I M206C/I76L F335L/A222L S243E/L246I R247M/V255I

V159L/V221F M206C/I76M F335L/E356S S243E/A272P R247M/F344G

V159L/V221I M206C/G138K F335L/ S109G S243E/ S353E R247M/I76L

V159L/G245S M206C/L238F F335L/I290L S243E/ S353K R247M/I76M

V159L/Q92C M206C/L238T F335L/I290M S243E/A256D R247M/G138K

V159L/Q92S M206C/I35L F335L/L330M S243E/A256E R247M/L238F

V159L/F230A M206C/I35V F335L/H131C S243E/R224L R247M/L238T

V159L/F230N M206C/C208A F335L/A189G S243E/A134M R247M/I35L

V159L/ S87P M206C/C208S F335L/Q193K S243E/V359E R247M/I35V

V159L/ S87Q M206C/E240A F335L/Q193R S243E/V359K R247M/C208A

V159L/L98H M206C/E240T F335L/L242I S243E/ S333A R247M/C208S

V159L/ S70K M206C/N148H F335L/Q108H S243E/ S333E R247M/E240A

V159L/F351A M206C/F94L F335L/F68V S243E/T352D R247M/E240T

V159L/F351V M206C/F94Y F335L/G100S S243E/T352E R247M/N148H

V159L/M157Y M206C/V150L F335L/G100T S243E/M157F R247M/F94L

V159L/C44F M206C/F68P F335L/L323I S243E/M157S R247M/F94Y

V159L/C44Y M206C/N148R F335L/L323M S243E/D14G R247M/V150L

V159L/I3L M206C/K361R F335L/Q277D S243E/D296A R247M/F68P

V159L/I3M M206C/Q280E F335L/Q277E S243E/D296L R247M/N148R

P129R/G181A M206C/Q280R F335L/C269N S243E/T314A R247M/K361R

P129R/G181S M206C/K225E F335L/C269T S243E/T314E R247M/Q280E

P129R/E1 1 1P M206C/K225G F335L/A326F S243E/F267Y R247M/Q280R

P129R/E1 1 1 S M206C/L238A F335L/A326I S243E/E71N R247M/K225E

P129R/F344Y M206C/L238S F335L/L152F S243E/E252Q R247M/K225G Positions Positions Positions Positions Positions

P129R/V165A M206C/C269A F335L/C282N S243E/I367V R247M/L238A

P129R/V218F M206C/C269I F335L/ S329P S243E/A31M R247M/L238S

P129R/N96S M206C/D296P F335L/I45D S243E/A31 S R247M/C269A

P129R/F347Y M206C/F140Y F335L/I45L S243E/F93A R247M/C269I

P129R/M206C M206C/I24L F335L/E258A S243E/L323C R247M/D296P

P129R/M206L M206C/I24V F335L/A272E S243E/L323V R247M/F140Y

P129R/P129V M206C/D170S F335L/T312A S243E/T83G R247M/I24L

P129R/T65A M206C/V229M F335L/T312R S243E/T83N R247M/I24V

P129R/I106V M206C/E360A F335L/M327Q S243E/Q92R R247M/D170S

P129R/P186Q M206C/ S322V F335L/M327T S243E/F267I R247M/V229M

P129R/M319I M206C/F347I F335L/N174Y S243E/F267Q R247M/E360A

P129R/M319V M206C/V221F F335L/L340I S243E/E4K R247M/ S322V

P129R/G245A M206C/V221I F335L/L340M S243E/E90D R247M/F347I

P129R/G245C M206C/G245S F335L/A189H S243E/T312K R247M/V221F

P129R/C282E M206C/Q92C F335L/A189Y S243E/T312N R247M/V221I

P129R/C282I M206C/Q92S F335L/N194R S243E/L241V R247M/G245S

P129R/F335L M206C/F230A F335L/N194S S243E/V255I R247M/Q92C

P129R/T248A M206C/F230N F335L/L169V S243E/F344G R247M/Q92S

P129R/T248D M206C/ S87P F335L/K225D S243E/I76L R247M/F230A

P129R/L284S M206C/ S87Q F335L/K225S S243E/I76M R247M/F230N

P129R/N350K M206C/L98H F335L/A63I S243E/G138K R247M/ S87P

P129R/N350R M206C/ S70K F335L/A63P S243E/L238F R247M/ S87Q

P129R/F132L M206C/F351A F335L/I180L S243E/L238T R247M/L98H

P129R/I287L M206C/F351V F335L/I180V S243E/I35L R247M/ S70K

P129R/V36I M206C/M157Y F335L/H151D S243E/I35V R247M/F351A

P129R/V36L M206C/C44F F335L/T220I S243E/C208A R247M/F351V

P129R/H131V M206C/C44Y F335L/T220S S243E/C208S R247M/M157Y

P129R/H131Y M206C/I3L F335L/L246I S243E/E240A R247M/C44F

P129R/ S243E M206C/I3M F335L/A272P S243E/E240T R247M/C44Y

P129R/I211L M206L/P129V F335L/ S353E S243E/N148H R247M/I3L

P129R/I21 1V M206L/T65A F335L/ S353K S243E/F94L R247M/I3M

P129R/I91F M206L/I106V F335L/A256D S243E/F94Y R247N/I91L

P129R/E360G M206L/P186Q F335L/A256E S243E/V150L R247N/I91V

P129R/E360L M206L/M319I F335L/R224L S243E/F68P R247N/M160H

P129R/A315R M206L/M319V F335L/A134M S243E/N148R R247N/L293F

P129R/A315S M206L/G245A F335L/V359E S243E/K361R R247N/L293S

P129R/C282S M206L/G245C F335L/V359K S243E/Q280E R247N/L66F

P129R/C282V M206L/C282E F335L/ S333A S243E/Q280R R247N/C282D

P129R/G135A M206L/C282I F335L/ S333E S243E/K225E R247N/A222H

P129R/V221C M206L/F335L F335L/T352D S243E/K225G R247N/A222L

P129R/V221M M206L/T248A F335L/T352E S243E/L238A R247N/E356S

P129R/R247M M206L/T248D F335L/M157F S243E/L238S R247N/ S109G Positions Positions Positions Positions Positions

P129R/R247N M206L/L284S F335L/M157S S243E/C269A R247N/I290L

P129R/I91L M206L/N350K F335L/D14G S243E/C269I R247N/I290M

P129R/I91V M206L/N350R F335L/D296A S243E/D296P R247N/L330M

P129R/M160H M206L/F132L F335L/D296L S243E/F140Y R247N/H131C

P129R/L293F M206L/I287L F335L/T314A S243E/I24L R247N/A189G

P129R/L293S M206L/V36I F335L/T314E S243E/I24V R247N/Q193K

P129R/L66F M206L/V36L F335L/F267Y S243E/D170S R247N/Q193R

P129R/C282D M206L/H131V F335L/E71N S243E/V229M R247N/L242I

P129R/A222H M206L/H131Y F335L/E252Q S243E/E360A R247N/Q108H

P129R/A222L M206L/ S243E F335L/I367V S243E/ S322V R247N/F68V

P129R/E356S M206L/I21 1L F335L/A31M S243E/F347I R247N/G100S

P129R/ S109G M206L/I21 1V F335L/A31 S S243E/V221F R247N/G100T

P129R/I290L M206L/I91F F335L/F93A S243E/V221I R247N/L323I

P129R/I290M M206L/E360G F335L/L323C S243E/G245S R247N/L323M

P129R/L330M M206L/E360L F335L/L323V S243E/Q92C R247N/Q277D

P129R/H131C M206L/A315R F335L/T83G S243E/Q92S R247N/Q277E

P129R/A189G M206L/A315S F335L/T83N S243E/F230A R247N/C269N

P129R/Q193K M206L/C282S F335L/Q92R S243E/F230N R247N/C269T

P129R/Q193R M206L/C282V F335L/F267I S243E/ S87P R247N/A326F

P129R/L242I M206L/G135A F335L/F267Q S243E/ S87Q R247N/A326I

P129R/Q108H M206L/V221C F335L/E4K S243E/L98H R247N/L152F

P129R/F68V M206L/V221M F335L/E90D S243E/ S70K R247N/C282N

P129R/G100S M206L/R247M F335L/T312K S243E/F351A R247N/ S329P

P129R/G100T M206L/R247N F335L/T312N S243E/F351V R247N/I45D

P129R/L323I M206L/I91L F335L/L241V S243E/M157Y R247N/I45L

P129R/L323M M206L/I91V F335L/V255I S243E/C44F R247N/E258A

P129R/Q277D M206L/M160H F335L/F344G S243E/C44Y R247N/A272E

P129R/Q277E M206L/L293F F335L/I76L S243E/I3L R247N/T312A

P129R/C269N M206L/L293S F335L/I76M S243E/I3M R247N/T312R

P129R/C269T M206L/L66F F335L/G138K I21 1L/I21 1V R247N/M327Q

P129R/A326F M206L/C282D F335L/L238F I21 1L/I91F R247N/M327T

P129R/A326I M206L/A222H F335L/L238T I21 1L/E360G R247N/N174Y

P129R/L152F M206L/A222L F335L/I35L I21 1L/E360L R247N/L340I

P129R/C282N M206L/E356S F335L/I35V I21 1L/A315R R247N/L340M

P129R/ S329P M206L/ S109G F335L/C208A I21 1L/A315S R247N/A189H

P129R/I45D M206L/I290L F335L/C208S I21 1L/C282S R247N/A189Y

P129R/I45L M206L/I290M F335L/E240A I21 1L/C282V R247N/N194R

P129R/E258A M206L/L330M F335L/E240T I21 1L/G135A R247N/N194S

P129R/A272E M206L/H131C F335L/N148H I21 1L/V221C R247N/L169V

P129R/T312A M206L/A189G F335L/F94L I21 1L/V221M R247N/K225D

P129R/T312R M206L/Q193K F335L/F94Y I21 1L/R247M R247N/K225S

P129R/M327Q M206L/Q193R F335L/V150L I21 1L/R247N R247N/A63I Positions Positions Positions Positions Positions

P129R/M327T M206L/L242I F335L/F68P I21 1L/I91L R247N/A63P

P129R/N174Y M206L/Q108H F335L/N148R I21 1L/I91V R247N/I180L

P129R/L340I M206L/F68V F335L/K361R I21 1L/M160H R247N/I180V

P129R/L340M M206L/G100S F335L/Q280E I21 1L/L293F R247N/H151D

P129R/A189H M206L/G100T F335L/Q280R I21 1L/L293S R247N/T220I

P129R/A189Y M206L/L323I F335L/K225E I21 1L/L66F R247N/T220S

P129R/N194R M206L/L323M F335L/K225G I21 1L/C282D R247N/L246I

P129R/N194S M206L/Q277D F335L/L238A I21 1L/A222H R247N/A272P

P129R/L169V M206L/Q277E F335L/L238S I211L/A222L R247N/ S353E

P129R/K225D M206L/C269N F335L/C269A I21 1L/E356S R247N/ S353K

P129R/K225S M206L/C269T F335L/C269I I21 1L/ S 109G R247N/A256D

P129R/A63I M206L/A326F F335L/D296P I21 1L/I290L R247N/A256E

P129R/A63P M206L/A326I F335L/F140Y I21 1L/I290M R247N/R224L

P129R/I180L M206L/L152F F335L/I24L I21 1L/L330M R247N/A134M

P129R/I180V M206L/C282N F335L/I24V I21 1L/H131C R247N/V359E

P129R/H151D M206L/ S329P F335L/D170S I21 1L/A189G R247N/V359K

P129R/T220I M206L/I45D F335L/V229M I21 1L/Q193K R247N/ S333A

P129R/T220S M206L/I45L F335L/E360A I21 1L/Q193R R247N/ S333E

P129R/L246I M206L/E258A F335L/ S322V I21 1L/L242I R247N/T352D

P129R/A272P M206L/A272E F335L/F347I I21 1L/Q108H R247N/T352E

P129R/ S353E M206L/T312A F335L/V221F I21 1L/F68V R247N/M157F

P129R/ S353K M206L/T312R F335L/V221I I21 1L/G100S R247N/M157S

P129R/A256D M206L/M327Q F335L/G245S I21 1L/G100T R247N/D14G

P129R/A256E M206L/M327T F335L/Q92C I21 1L/L323I R247N/D296A

P129R/R224L M206L/N174Y F335L/Q92S I21 1L/L323M R247N/D296L

P129R/A134M M206L/L340I F335L/F230A I21 1L/Q277D R247N/T314A

P129R/V359E M206L/L340M F335L/F230N I21 1L/Q277E R247N/T314E

P129R/V359K M206L/A189H F335L/ S87P I21 1L/C269N R247N/F267Y

P129R/ S333A M206L/A189Y F335L/ S87Q I21 1L/C269T R247N/E71N

P129R/ S333E M206L/N194R F335L/L98H I21 1L/A326F R247N/E252Q

P129R/T352D M206L/N194S F335L/ S70K I21 1L/A326I R247N/I367V

P129R/T352E M206L/L169V F335L/F351A I21 1L/L152F R247N/A31M

P129R/M157F M206L/K225D F335L/F351V I21 1L/C282N R247N/A31 S

P129R/M157S M206L/K225S F335L/M157Y I21 1L/ S329P R247N/F93A

P129R/D14G M206L/A63I F335L/C44F I21 1L/I45D R247N/L323C

P129R/D296A M206L/A63P F335L/C44Y I21 1L/I45L R247N/L323V

P129R/D296L M206L/I180L F335L/I3L I21 1L/E258A R247N/T83G

P129R/T314A M206L/I180V F335L/I3M I21 1L/A272E R247N/T83N

P129R/T314E M206L/H151D T248A/T248D I211L/T312A R247N/Q92R

P129R/F267Y M206L/T220I T248A/L284S I21 1L/T312R R247N/F267I

P129R/E71N M206L/T220S T248A/N350K I21 1L/M327Q R247N/F267Q

P129R/E252Q M206L/L246I T248A/N350R I21 1L/M327T R247N/E4K Positions Positions Positions Positions Positions

P129R/I367V M206L/A272P T248A/F132L I21 1L/N174Y R247N/E90D

P129R/A31M M206L/ S353E T248A/I287L I21 1L/L340I R247N/T312K

P129R/A31 S M206L/ S353K T248A/V36I I21 1L/L340M R247N/T312N

P129R/F93A M206L/A256D T248A/V36L I21 1L/A189H R247N/L241V

P129R/L323C M206L/A256E T248A/H131V I21 1L/A189Y R247N/V255I

P129R/L323V M206L/R224L T248A/H131Y I21 1L/N194R R247N/F344G

P129R/T83G M206L/A134M T248A/ S243E I21 1L/N194S R247N/I76L

P129R/T83N M206L/V359E T248A/I21 1L I21 1L/L169V R247N/I76M

P129R/Q92R M206L/V359K T248A/I21 1V I21 1L/K225D R247N/G138K

P129R/F267I M206L/ S333A T248A/I91F I21 1L/K225S R247N/L238F

P129R/F267Q M206L/ S333E T248A/E360G I21 1L/A63I R247N/L238T

P129R/E4K M206L/T352D T248A/E360L I21 1L/A63P R247N/I35L

P129R/E90D M206L/T352E T248A/A315R I211L/I180L R247N/I35V

P129R/T312K M206L/M157F T248A/A315S I21 1L/I180V R247N/C208A

P129R/T312N M206L/M157S T248A/C282S I21 1L/H151D R247N/C208S

P129R/L241V M206L/D14G T248A/C282V I211L/T220I R247N/E240A

P129R/V255I M206L/D296A T248A/G135A I21 1L/T220S R247N/E240T

P129R/F344G M206L/D296L T248A/V221C I211L/L246I R247N/N148H

P129R/I76L M206L/T314A T248A/V221M I21 1L/A272P R247N/F94L

P129R/I76M M206L/T314E T248A/R247M I21 1L/ S353E R247N/F94Y

P129R/G138K M206L/F267Y T248A/R247N I21 1L/ S353K R247N/V150L

P129R/L238F M206L/E71N T248A/I91L I21 1L/A256D R247N/F68P

P129R/L238T M206L/E252Q T248A/I91V I21 1L/A256E R247N/N148R

P129R/I35L M206L/I367V T248A/M160H I21 1L/R224L R247N/K361R

P129R/I35V M206L/A31M T248A/L293F I21 1L/A134M R247N/Q280E

P129R/C208A M206L/A31 S T248A/L293S I211L/V359E R247N/Q280R

P129R/C208S M206L/F93A T248A/L66F I21 1L/V359K R247N/K225E

P129R/E240A M206L/L323C T248A/C282D I21 1L/ S333A R247N/K225G

P129R/E240T M206L/L323V T248A/A222H I21 1L/ S333E R247N/L238A

P129R/N148H M206L/T83G T248A/A222L I21 1L/T352D R247N/L238S

P129R/F94L M206L/T83N T248A/E356S I21 1L/T352E R247N/C269A

P129R/F94Y M206L/Q92R T248A/ S109G I21 1L/M157F R247N/C269I

P129R/V150L M206L/F267I T248A/I290L I21 1L/M157S R247N/D296P

P129R/F68P M206L/F267Q T248A/I290M I21 1L/D14G R247N/F140Y

P129R/N148R M206L/E4K T248A/L330M I21 1L/D296A R247N/I24L

P129R/K361R M206L/E90D T248A/H131C I21 1L/D296L R247N/I24V

P129R/Q280E M206L/T312K T248A/A189G I211L/T314A R247N/D170S

P129R/Q280R M206L/T312N T248A/Q193K I21 1L/T314E R247N/V229M

P129R/K225E M206L/L241V T248A/Q193R I21 1L/F267Y R247N/E360A

P129R/K225G M206L/V255I T248A/L242I I21 1L/E71N R247N/ S322V

P129R/L238A M206L/F344G T248A/Q108H I211L/E252Q R247N/F347I

P129R/L238S M206L/I76L T248A/F68V I21 1L/I367V R247N/V221F Positions Positions Positions Positions Positions

P129R/C269A M206L/I76M T248A/G100S I211L/A31M R247N/V221I

P129R/C269I M206L/G138K T248A/G100T I21 1L/A31 S R247N/G245S

P129R/D296P M206L/L238F T248A/L323I I21 1L/F93A R247N/Q92C

P129R/F140Y M206L/L238T T248A/L323M I21 1L/L323C R247N/Q92S

P129R/I24L M206L/I35L T248A/Q277D I211L/L323V R247N/F230A

P129R/I24V M206L/I35V T248A/Q277E I21 1L/T83G R247N/F230N

P129R/D170S M206L/C208A T248A/C269N I21 1L/T83N R247N/ S87P

P129R/V229M M206L/C208S T248A/C269T I21 1L/Q92R R247N/ S87Q

P129R/E360A M206L/E240A T248A/A326F I21 1L/F267I R247N/L98H

P129R/ S322V M206L/E240T T248A/A326I I21 1L/F267Q R247N/ S70K

P129R/F347I M206L/N148H T248A/L152F I211L/E4K R247N/F351A

P129R/V221F M206L/F94L T248A/C282N I21 1L/E90D R247N/F351V

P129R/V221I M206L/F94Y T248A/ S329P I211L/T312K R247N/M157Y

P129R/G245S M206L/V150L T248A/I45D I21 1L/T312N R247N/C44F

P129R/Q92C M206L/F68P T248A/I45L I21 1L/L241V R247N/C44Y

P129R/Q92S M206L/N148R T248A/E258A I21 1L/V255I R247N/I3L

P129R/F230A M206L/K361R T248A/A272E I21 1L/F344G R247N/I3M

P129R/F230N M206L/Q280E T248A/T312A I21 1L/I76L I91L/I91V

P129R/ S87P M206L/Q280R T248A/T312R I211L/I76M I91L/M160H

P129R/ S87Q M206L/K225E T248A/M327Q I21 1L/G138K I91L/L293F

P129R/L98H M206L/K225G T248A/M327T I21 1L/L238F I91L/L293S

P129R/ S70K M206L/L238A T248A/N174Y I21 1L/L238T I91L/L66F

P129R/F351A M206L/L238S T248A/L340I I21 1L/I35L I91L/C282D

P129R/F351V M206L/C269A T248A/L340M I21 1L/I35V I91L/A222H

P129R/M157Y M206L/C269I T248A/A189H I21 1L/C208A I91L/A222L

P129R/C44F M206L/D296P T248A/A189Y I21 1L/C208S I91L/E356S

P129R/C44Y M206L/F140Y T248A/N194R I21 1L/E240A I91L/ S109G

P129R/I3L M206L/I24L T248A/N194S I21 1L/E240T I91L/I290L

P129R/I3M M206L/I24V T248A/L169V I21 1L/N148H I91L/I290M

G181A/G181 S M206L/D170S T248A/K225D I21 1L/F94L I91L/L330M

G181A/E1 1 1P M206L/V229M T248A/K225S I21 1L/F94Y I91L/H131C

G181A/E1 1 1 S M206L/E360A T248A/A63I I21 1L/V150L I91L/A189G

G181A/F344Y M206L/ S322V T248A/A63P I21 1L/F68P I91L/Q193K

G181A/V165A M206L/F347I T248A/I180L I21 1L/N148R I91L/Q193R

G181A/V218F M206L/V221F T248A/I180V I21 1L/K361R I91L/L242I

G181A/N96S M206L/V221I T248A/H151D I211L/Q280E I91L/Q108H

G181A/F347Y M206L/G245S T248A/T220I I21 1L/Q280R I91L/F68V

G181A/M206C M206L/Q92C T248A/T220S I211L/K225E I91L/G100S

G181A/M206L M206L/Q92S T248A/L246I I21 1L/K225G I91L/G100T

G181A/P129V M206L/F230A T248A/A272P I211L/L238A I91L/L323I

G181A/T65A M206L/F230N T248A/ S353E I21 1L/L238S I91L/L323M

G181A/I106V M206L/ S87P T248A/ S353K I21 1L/C269A I91L/Q277D Positions Positions Positions Positions Positions

G181A/P186Q M206L/ S87Q T248A/A256D I21 1L/C269I I91L/Q277E

G181A/M319I M206L/L98H T248A/A256E I21 1L/D296P I91L/C269N

G181A/M319V M206L/ S70K T248A/R224L I21 1L/F140Y I91L/C269T

G181A/G245A M206L/F351A T248A/A134M I21 1L/I24L I91L/A326F

G181A/G245C M206L/F351V T248A/V359E I21 1L/I24V I91L/A326I

G181A/C282E M206L/M157Y T248A/V359K I21 1L/D170S I91L/L152F

G181A/C282I M206L/C44F T248A/ S333A I21 1L/V229M I91L/C282N

G181A/F335L M206L/C44Y T248A/ S333E I211L/E360A I91L/ S329P

G181A/T248A M206L/I3L T248A/T352D I21 1L/ S322V I91L/I45D

G181A/T248D M206L/I3M T248A/T352E I21 1L/F347I I91L/I45L

G181A/L284S P129V/T65A T248A/M157F I21 1L/V221F I91L/E258A

G181A/N350K P129V/I106V T248A/M157S I21 1L/V221I I91L/A272E

G181A/N350R P129V/P186Q T248A/D14G I21 1L/G245S I91L/T312A

G181A/F132L P129V/M319I T248A/D296A I21 1L/Q92C I91L/T312R

G181A/I287L P129V/M319V T248A/D296L I21 1L/Q92S I91L/M327Q

G181A/V36I P129V/G245A T248A/T314A I21 1L/F230A I91L/M327T

G181A/V36L P129V/G245C T248A/T314E I21 1L/F230N I91L/N174Y

G181A/H131V P129V/C282E T248A/F267Y I21 1L/ S87P I91L/L340I

G181A/H131Y P129V/C282I T248A/E71N I21 1L/ S87Q I91L/L340M

G181A/ S243E P129V/F335L T248A/E252Q I21 1L/L98H I91L/A189H

G181A/I21 1L P129V/T248A T248A/I367V I21 1L/ S70K I91L/A189Y

G181A/I21 1V P129V/T248D T248A/A31M I21 1L/F351A I91L/N194R

G181A/I91F P129V/L284S T248A/A31 S I21 1L/F351V I91L/N194S

G181A/E360G P129V/N350K T248A/F93A I21 1L/M157Y I91L/L169V

G181A/E360L P129V/N350R T248A/L323C I211L/C44F I91L/K225D

G181A/A315R P129V/F132L T248A/L323V I21 1L/C44Y I91L/K225S

G181A/A315S P129V/I287L T248A/T83G I21 1L/I3L I91L/A63I

G181A/C282S P129V/V36I T248A/T83N I21 1L/I3M I91L/A63P

G181A/C282V P129V/V36L T248A/Q92R I21 1V/I91F I91L/I180L

G181A/G135A P129V/H131V T248A/F267I I21 1V/E360G I91L/I180V

G181A/V221C P129V/H131Y T248A/F267Q I211V/E360L I91L/H151D

G181A/V221M P129V/ S243E T248A/E4K I21 1V/A315R I91L/T220I

G181A/R247M P129V/I21 1L T248A/E90D I21 1V/A315S I91L/T220S

G181A/R247N P129V/I21 1V T248A/T312K I211V/C282S I91L/L246I

G181A/I91L P129V/I91F T248A/T312N I21 1V/C282V I91L/A272P

G181A/I91V P129V/E360G T248A/L241V I211V/G135A I91L/ S353E

G181A/M160H P129V/E360L T248A/V255I I21 1V/V221C I91L/ S353K

G181A/L293F P129V/A315R T248A/F344G I211V/V221M I91L/A256D

G181A/L293S P129V/A315S T248A/I76L I21 1V/R247M I91L/A256E

G181A/L66F P129V/C282S T248A/I76M I21 1V/R247N I91L/R224L

G181A/C282D P129V/C282V T248A/G138K I21 1V/I91L I91L/A134M

G181A/A222H P129V/G135A T248A/L238F I21 1V/I91V I91L/V359E Positions Positions Positions Positions Positions

G181A/A222L P129V/V221C T248A/L238T I21 1V/M160H I91L/V359K

G181A/E356S P129V/V221M T248A/I35L I21 1V/L293F I91L/ S333A

G181A/ S109G P129V/R247M T248A/I35V I21 1V/L293S I91L/ S333E

G181A/I290L P129V/R247N T248A/C208A I21 1V/L66F I91L/T352D

G181A/I290M P129V/I91L T248A/C208S I21 1V/C282D I91L/T352E

G181A/L330M P129V/I91V T248A/E240A I211V/A222H I91L/M157F

G181A/H131C P129V/M160H T248A/E240T I21 1V/A222L I91L/M157S

G181A/A189G P129V/L293F T248A/N148H I21 1V/E356S I91L/D14G

G181A/Q193K P129V/L293S T248A/F94L I21 1V/ S109G I91L/D296A

G181A/Q193R P129V/L66F T248A/F94Y I21 1V/I290L I91L/D296L

G181A/L242I P129V/C282D T248A/V150L I21 1V/I290M I91L/T314A

G181A/Q108H P129V/A222H T248A/F68P I21 1V/L330M I91L/T314E

G181A/F68V P129V/A222L T248A/N148R I21 1V/H131C I91L/F267Y

G181A/G100S P129V/E356S T248A/K361R I211V/A189G I91L/E71N

G181A/G100T P129V/ S109G T248A/Q280E I21 1V/Q193K I91L/E252Q

G181A/L323I P129V/I290L T248A/Q280R I21 1V/Q193R I91L/I367V

G181A/L323M P129V/I290M T248A/K225E I21 1V/L242I I91L/A31M

G181A/Q277D P129V/L330M T248A/K225G I211V/Q108H I91L/A31 S

G181A/Q277E P129V/H131C T248A/L238A I21 1V/F68V I91L/F93A

G181A/C269N P129V/A189G T248A/L238S I21 1V/G100S I91L/L323C

G181A/C269T P129V/Q193K T248A/C269A I21 1V/G100T I91L/L323V

G181A/A326F P129V/Q193R T248A/C269I I21 1V/L323I I91L/T83G

G181A/A326I P129V/L242I T248A/D296P I21 1V/L323M I91L/T83N

G181A/L152F P129V/Q108H T248A/F140Y I211V/Q277D I91L/Q92R

G181A/C282N P129V/F68V T248A/I24L I21 1V/Q277E I91L/F267I

G181A/ S329P P129V/G100S T248A/I24V I21 1V/C269N I91L/F267Q

G181A/I45D P129V/G100T T248A/D170S I21 1V/C269T I91L/E4K

G181A/I45L P129V/L323I T248A/V229M I21 1V/A326F I91L/E90D

G181A/E258A P129V/L323M T248A/E360A I21 1V/A326I I91L/T312K

G181A/A272E P129V/Q277D T248A/ S322V I21 1V/L152F I91L/T312N

G181A/T312A P129V/Q277E T248A/F347I I21 1V/C282N I91L/L241V

G181A/T312R P129V/C269N T248A/V221F I21 1V/ S329P I91L/V255I

G181A/M327Q P129V/C269T T248A/V221I I21 1V/I45D I91L/F344G

G181A/M327T P129V/A326F T248A/G245S I21 1V/I45L I91L/I76L

G181A/N174Y P129V/A326I T248A/Q92C I21 1V/E258A I91L/I76M

G181A/L340I P129V/L152F T248A/Q92S I21 1V/A272E I91L/G138K

G181A/L340M P129V/C282N T248A/F230A I21 1V/T312A I91L/L238F

G181A/A189H P129V/ S329P T248A/F230N I21 1V/T312R I91L/L238T

G181A/A189Y P129V/I45D T248A/ S87P I21 1V/M327Q I91L/I35L

G181A/N194R P129V/I45L T248A/ S87Q I21 1V/M327T I91L/I35V

G181A/N194S P129V/E258A T248A/L98H I21 1V/N174Y I91L/C208A

G181A/L169V P129V/A272E T248A/ S70K I21 1V/L340I I91L/C208S Positions Positions Positions Positions Positions

G181A/K225D P129V/T312A T248A/F351A I211V/L340M I91L/E240A

G181A/K225S P129V/T312R T248A/F351V I211V/A189H I91L/E240T

G181A/A63I P129V/M327Q T248A/M157Y I211V/A189Y I91L/N148H

G181A/A63P P129V/M327T T248A/C44F I211V/N194R I91L/F94L

G181A/I180L P129V/N174Y T248A/C44Y I211V/N194S I91L/F94Y

G181A/I180V P129V/L340I T248A/I3L I211V/L169V I91L/V150L

G181A/H151D P129V/L340M T248A/I3M I211V/K225D I91L/F68P

G181A/T220I P129V/A189H T248D/L284S I211V/K225S I91L/N148R

G181A/T220S P129V/A189Y T248D/N350K I211V/A63I I91L/K361R

G181A/L246I P129V/N194R T248D/N350R I211V/A63P I91L/Q280E

G181A/A272P P129V/N194S T248D/F132L I211V/I180L I91L/Q280R

G181A/S353E P129V/L169V T248D/I287L I211V/I180V I91L/K225E

G181A/S353K P129V/K225D T248D/V36I I211V/H151D I91L/K225G

G181A/A256D P129V/K225S T248D/V36L I211V/T220I I91L/L238A

G181A/A256E P129V/A63I T248D/H131V I211V/T220S I91L/L238S

G181A/R224L P129V/A63P T248D/H131Y I211V/L246I I91L/C269A

G181A/A134M P129V/I180L T248D/S243E I211V/A272P I91L/C269I

G181A/V359E P129V/I180V T248D/I211L I211V/S353E I91L/D296P

G181A/V359K P129V/H151D T248D/I211V I211V/S353K I91L/F140Y

G181A/S333A P129V/T220I T248D/I91F I211V/A256D I91L/I24L

G181A/S333E P129V/T220S T248D/E360G I211V/A256E I91L/I24V

G181A/T352D P129V/L246I T248D/E360L I211V/R224L I91L/D170S

G181A/T352E P129V/A272P T248D/A315R I211V/A134M I91L/V229M

G181A/M157F P129V/S353E T248D/A315S I211V/V359E I91L/E360A

G181A/M157S P129V/S353K T248D/C282S I211V/V359K I91L/S322V

G181A/D14G P129V/A256D T248D/C282V I211V/S333A I91L/F347I

G181A/D296A P129V/A256E T248D/G135A I211V/S333E I91L/V221F

G181A/D296L P129V/R224L T248D/V221C I211V/T352D I91L/V221I

G181A/T314A P129V/A134M T248D/V221M I211V/T352E I91L/G245S

G181A/T314E P129V/V359E T248D/R247M I211V/M157F I91L/Q92C

G181A/F267Y P129V/V359K T248D/R247N I211V/M157S I91L/Q92S

G181A/E71N P129V/S333A T248D/I91L I211V/D14G I91L/F230A

G181A/E252Q P129V/S333E T248D/I91V I211V/D296A I91L/F230N

G181A/I367V P129V/T352D T248D/M160H I211V/D296L I91L/S87P

G181A/A31M P129V/T352E T248D/L293F I211V/T314A I91L/S87Q

G181A/A31S P129V/M157F T248D/L293S I211V/T314E I91L/L98H

G181A/F93A P129V/M157S T248D/L66F I211V/F267Y I91L/S70K

G181A/L323C P129V/D14G T248D/C282D I211V/E71N I91L/F351A

G181A/L323V P129V/D296A T248D/A222H I211V/E252Q I91L/F351V

G181A/T83G P129V/D296L T248D/A222L I211V/I367V I91L/M157Y

G181A/T83N P129V/T314A T248D/E356S I211V/A31M I91L/C44F

G181A/Q92R P129V/T314E T248D/S109G I211V/A31S I91L/C44Y Positions Positions Positions Positions Positions

G181A/F267I P129V/F267Y T248D/I290L I211V/F93A I91L/I3L

G181A/F267Q P129V/E71N T248D/I290M I211V/L323C I91L/I3M

G181A/E4K P129V/E252Q T248D/L330M I211V/L323V I91V/M160H

G181A/E90D PI 29V/ 1367V T248D/H131C I211V/T83G I91V/L293F

G181A/T312K P129V/A31M T248D/A189G I211V/T83N I91V/L293S

G181A/T312N P 129V/ A3 IS T248D/Q193K I211V/Q92R I91V/L66F

G181A/L241V P129V/F93A T248D/Q193R I211V/F267I I91V/C282D

G181A/V255I P129V/L323C T248D/L242I I211V/F267Q I91V/A222H

G181A/F344G P129V/L323V T248D/Q108H I211V/E4K I91V/A222L

G181A/I76L P129V/T83G T248D/F68V I211V/E90D I91V/E356S

G181A/I76M P129V/T83N T248D/G100S I211V/T312K I91V/S109G

G181A/G138K P129V/Q92R T248D/G100T I211V/T312N I91V/I290L

G181A/L238F P129V/F267I T248D/L323I I211V/L241V I91V/I290M

G181A/L238T P129V/F267Q T248D/L323M I211V/V255I I91V/L330M

G181A/I35L P129V/E4K T248D/Q277D I211V/F344G I91V/H131C

G181A/I35V P129V/E90D T248D/Q277E I211V/I76L I91V/A189G

G181A/C208A P129V/T312K T248D/C269N I211V/I76M I91V/Q193K

G181A/C208S P129V/T312N T248D/C269T I211V/G138K I91V/Q193R

G181A/E240A P129V/L241V T248D/A326F I211V/L238F I91V/L242I

G181A/E240T P129V/V255I T248D/A326I I211V/L238T I91V/Q108H

G181A/N148H P129V/F344G T248D/L152F I211V/I35L I91V/F68V

G181A/F94L P129V/I76L T248D/C282N I211V/I35V I91V/G100S

G181A/F94Y P129V/I76M T248D/S329P I211V/C208A I91V/G100T

G181A/V150L P129V/G138K T248D/I45D I211V/C208S I91V/L323I

G181A/F68P P129V/L238F T248D/I45L I211V/E240A I91V/L323M

G181A/N148R P129V/L238T T248D/E258A I211V/E240T I91V/Q277D

G181A/K361R P129V/I35L T248D/A272E I211V/N148H I91V/Q277E

G181A/Q280E P129V/I35V T248D/T312A I211V/F94L I91V/C269N

G181A/Q280R P129V/C208A T248D/T312R I211V/F94Y I91V/C269T

G181A/K225E P129V/C208S T248D/M327Q I211V/V150L I91V/A326F

G181A/K225G P129V/E240A T248D/M327T I211V/F68P I91V/A326I

G181A/L238A P129V/E240T T248D/N174Y I211V/N148R I91V/L152F

G181A/L238S P129V/N148H T248D/L340I I211V/K361R I91V/C282N

G181A/C269A P129V/F94L T248D/L340M I211V/Q280E I91V/S329P

G181A/C269I P129V/F94Y T248D/A189H I211V/Q280R I91V/I45D

G181A/D296P P129V/V150L T248D/A189Y I211V/K225E I91V/I45L

G181A/F140Y P129V/F68P T248D/N194R I211V/K225G I91V/E258A

G181A/I24L P129V/N148R T248D/N194S I211V/L238A I91V/A272E

G181A/I24V P129V/K361R T248D/L169V I211V/L238S I91V/T312A

G181A/D170S P129V/Q280E T248D/K225D I211V/C269A I91V/T312R

G181A/V229M P129V/Q280R T248D/K225S I211V/C269I I91V/M327Q

G181A/E360A P129V/K225E T248D/A63I I211V/D296P I91V/M327T Positions Positions Positions Positions Positions

G181A/S322V P129V/K225G T248D/A63P I211V/F140Y I91V/N174Y

G181A/F347I P129V/L238A T248D/I180L I211V/I24L I91V/L340I

G181A/V221F P129V/L238S T248D/I180V I211V/I24V I91V/L340M

G181A/V221I P129V/C269A T248D/H151D I211V/D170S I91V/A189H

G181A/G245S P129V/C269I T248D/T220I I211V/V229M I91V/A189Y

G181A/Q92C P129V/D296P T248D/T220S I211V/E360A I91V/N194R

G181A/Q92S P129V/F140Y T248D/L246I I211V/S322V I91V/N194S

G181A/F230A P129V/I24L T248D/A272P I211V/F347I I91V/L169V

G181A/F230N P129V/I24V T248D/S353E I211V/V221F I91V/K225D

G181A/S87P P129V/D170S T248D/S353K I211V/V221I I91V/K225S

G181A/S87Q P129V/V229M T248D/A256D I211V/G245S I91V/A63I

G181A/L98H P129V/E360A T248D/A256E I211V/Q92C I91V/A63P

G181A/S70K P129V/S322V T248D/R224L I211V/Q92S I91V/I180L

G181A/F351A P129V/F347I T248D/A134M I211V/F230A I91V/I180V

G181A/F351V P129V/V221F T248D/V359E I211V/F230N I91V/H151D

G181A/M157Y P129V/V221I T248D/V359K I211V/S87P I91V/T220I

G181A/C44F P129V/G245S T248D/S333A I211V/S87Q I91V/T220S

G181A/C44Y P129V/Q92C T248D/S333E I211V/L98H I91V/L246I

G181A/I3L P129V/Q92S T248D/T352D I211V/S70K I91V/A272P

G181A/I3M P129V/F230A T248D/T352E I211V/F351A I91V/S353E

G181S/E111P P129V/F230N T248D/M157F I211V/F351V I91V/S353K

G181S/E111S P129V/S87P T248D/M157S I211V/M157Y I91V/A256D

G181S/F344Y P129V/S87Q T248D/D14G I211V/C44F I91V/A256E

G181S/V165A P129V/L98H T248D/D296A I211V/C44Y I91V/R224L

G181S/V218F P129V/S70K T248D/D296L I211V/I3L I91V/A134M

G181S/N96S P129V/F351A T248D/T314A I211V/I3M I91V/V359E

G181S/F347Y P129V/F351V T248D/T314E I91F/E360G I91V/V359K

G181S/M206C P129V/M157Y T248D/F267Y I91F/E360L I91V/S333A

G181S/M206L P129V/C44F T248D/E71N I91F/A315R I91V/S333E

G181S/P129V P129V/C44Y T248D/E252Q I91F/A315S I91V/T352D

G181S/T65A P129V/I3L T248D/I367V I91F/C282S I91V/T352E

G181S/I106V P129V/I3M T248D/A31M I91F/C282V I91V/M157F

G181S/P186Q T65A/I106V T248D/A31S I91F/G135A I91V/M157S

G181S/M319I T65A/P186Q T248D/F93A I91F/V221C I91V/D14G

G181S/M319V T65A/M319I T248D/L323C I91F/V221M I91V/D296A

G181S/G245A T65A/M319V T248D/L323V I91F/R247M I91V/D296L

G181S/G245C T65A/G245A T248D/T83G I91F/R247N I91V/T314A

G181S/C282E T65A/G245C T248D/T83N I91F/I91L I91V/T314E

G181S/C282I T65A/C282E T248D/Q92R I91F/I91V I91V/F267Y

G181S/F335L T65A/C282I T248D/F267I I91F/M160H I91V/E71N

G181S/T248A T65A/F335L T248D/F267Q I91F/L293F I91V/E252Q

G181S/T248D T65A/T248A T248D/E4K I91F/L293S I91V/I367V Positions Positions Positions Positions Positions

G181S/L284S T65A/T248D T248D/E90D I91F/L66F I91V/A31M

G181S/N350K T65A/L284S T248D/T312K I91F/C282D I91V/A31S

G181S/N350R T65A/N350K T248D/T312N I91F/A222H I91V/F93A

G181S/F132L T65A/N350R T248D/L241V I91F/A222L I91V/L323C

G181S/I287L T65A/F132L T248D/V255I I91F/E356S I91V/L323V

G181S/V36I T65A/I287L T248D/F344G I91F/S109G I91V/T83G

G181S/V36L T65A/V36I T248D/I76L I91F/I290L I91V/T83N

G181S/H131V T65A/V36L T248D/I76M I91F/I290M I91V/Q92R

G181S/H131Y T65A/H131V T248D/G138K I91F/L330M I91V/F267I

G181S/S243E T65A/H131Y T248D/L238F I91F/H131C I91V/F267Q

G181S/I211L T65A/S243E T248D/L238T I91F/A189G I91V/E4K

G181S/I211V T65A/I211L T248D/I35L I91F/Q193K I91V/E90D

G181S/I91F T65A/I211V T248D/I35V I91F/Q193R I91V/T312K

G181S/E360G T65A/I91F T248D/C208A I91F/L242I I91V/T312N

G181S/E360L T65A/E360G T248D/C208S I91F/Q108H I91V/L241V

G181S/A315R T65A/E360L T248D/E240A I91F/F68V I91V/V255I

G181S/A315S T65A/A315R T248D/E240T I91F/G100S I91V/F344G

G181S/C282S T65A/A315S T248D/N148H I91F/G100T I91V/I76L

G181S/C282V T65A/C282S T248D/F94L I91F/L323I I91V/I76M

G181S/G135A T65A/C282V T248D/F94Y I91F/L323M I91V/G138K

G181S/V221C T65A/G135A T248D/V150L I91F/Q277D I91V/L238F

G181S/V221M T65A/V221C T248D/F68P I91F/Q277E I91V/L238T

G181S/R247M T65A/V221M T248D/N148R I91F/C269N I91V/I35L

G181S/R247N T65A/R247M T248D/K361R I91F/C269T I91V/I35V

G181S/I91L T65A/R247N T248D/Q280E I91F/A326F I91V/C208A

G181S/I91V T65A/I91L T248D/Q280R I91F/A326I I91V/C208S

G181S/M160H T65A/I91V T248D/K225E I91F/L152F I91V/E240A

G181S/L293F T65A/M160H T248D/K225G I91F/C282N I91V/E240T

G181S/L293S T65A/L293F T248D/L238A I91F/S329P I91V/N148H

G181S/L66F T65A/L293S T248D/L238S I91F/I45D I91V/F94L

G181S/C282D T65A/L66F T248D/C269A I91F/I45L I91V/F94Y

G181S/A222H T65A/C282D T248D/C269I I91F/E258A I91V/V150L

G181S/A222L T65A/A222H T248D/D296P I91F/A272E I91V/F68P

G181S/E356S T65A/A222L T248D/F140Y I91F/T312A I91V/N148R

G181S/S109G T65A/E356S T248D/I24L I91F/T312R I91V/K361R

G181S/I290L T65A/S109G T248D/I24V I91F/M327Q I91V/Q280E

G181S/I290M T65A/I290L T248D/D170S I91F/M327T I91V/Q280R

G181S/L330M T65A/I290M T248D/V229M I91F/N174Y I91V/K225E

G181S/H131C T65A/L330M T248D/E360A I91F/L340I I91V/K225G

G181S/A189G T65A/H131C T248D/S322V I91F/L340M I91V/L238A

G181S/Q193K T65A/A189G T248D/F347I I91F/A189H I91V/L238S

G181S/Q193R T65A/Q193K T248D/V221F I91F/A189Y I91V/C269A Positions Positions Positions Positions Positions

G181S/L242I T65A/Q193R T248D/V221I I91F/N194R I91V/C269I

G181S/Q108H T65A/L242I T248D/G245S I91F/N194S I91V/D296P

G181S/F68V T65A/Q108H T248D/Q92C I91F/L169V I91V/F140Y

G181S/G100S T65A/F68V T248D/Q92S I91F/K225D I91V/I24L

G181S/G100T T65A/G100S T248D/F230A I91F/K225S I91V/I24V

G181S/L323I T65A/G100T T248D/F230N I91F/A63I I91V/D170S

G181S/L323M T65A/L323I T248D/S87P I91F/A63P I91V/V229M

G181S/Q277D T65A/L323M T248D/S87Q I91F/I180L I91V/E360A

G181S/Q277E T65A/Q277D T248D/L98H I91F/I180V I91V/S322V

G181S/C269N T65A/Q277E T248D/S70K I91F/H151D I91V/F347I

G181S/C269T T65A/C269N T248D/F351A I91F/T220I I91V/V221F

G181S/A326F T65A/C269T T248D/F351V I91F/T220S I91V/V221I

G181S/A326I T65A/A326F T248D/M157Y I91F/L246I I91V/G245S

G181S/L152F T65A/A326I T248D/C44F I91F/A272P I91V/Q92C

G181S/C282N T65A/L152F T248D/C44Y I91F/S353E I91V/Q92S

G181S/S329P T65A/C282N T248D/I3L I91F/S353K I91V/F230A

G181S/I45D T65A/S329P T248D/I3M I91F/A256D I91V/F230N

G181S/I45L T65A/I45D L284S/N350K I91F/A256E I91V/S87P

G181S/E258A T65A/I45L L284S/N350R I91F/R224L I91V/S87Q

G181S/A272E T65A/E258A L284S/F132L I91F/A134M I91V/L98H

G181S/T312A T65A/A272E L284S/I287L I91F/V359E I91V/S70K

G181S/T312R T65A/T312A L284S/V36I I91F/V359K I91V/F351A

G181S/M327Q T65A/T312R L284S/V36L I91F/S333A I91V/F351V

G181S/M327T T65A/M327Q L284S/H131V I91F/S333E I91V/M157Y

G181S/N174Y T65A/M327T L284S/H131Y I91F/T352D I91V/C44F

G181S/L340I T65A/N174Y L284S/S243E I91F/T352E I91V/C44Y

G181S/L340M T65A/L340I L284S/I211L I91F/M157F I91V/I3L

G181S/A189H T65A/L340M L284S/I211V I91F/M157S I91V/I3M

G181S/A189Y T65A/A189H L284S/I91F I91F/D14G M160H/L293F

G181S/N194R T65A/A189Y L284S/E360G I91F/D296A M160H/L293S

G181S/N194S T65A/N194R L284S/E360L I91F/D296L M160H/L66F

G181S/L169V T65A/N194S L284S/A315R I91F/T314A M160H/C282D

G181S/K225D T65A/L169V L284S/A315S I91F/T314E M160H/A222H

G181S/K225S T65A/K225D L284S/C282S I91F/F267Y M160H/A222L

G181S/A63I T65A/K225S L284S/C282V I91F/E71N M160H/E356S

G181S/A63P T65A/A63I L284S/G135A I91F/E252Q M160H/S109G

G181S/I180L T65A/A63P L284S/V221C I91F/I367V M160H/I290L

G181S/I180V T65A/I180L L284S/V221M I91F/A31M M160H/I290M

G181S/H151D T65A/I180V L284S/R247M I91F/A31S M160H/L330M

G181S/T220I T65A/H151D L284S/R247N I91F/F93A M160H/H131C

G181S/T220S T65A/T220I L284S/I91L I91F/L323C M160H/A189G

G181S/L246I T65A/T220S L284S/I91V I91F/L323V M160H/Q193K Positions Positions Positions Positions Positions

G181S/A272P T65A/L246I L284S/M160H I91F/T83G M160H/Q193R

G181S/S353E T65A/A272P L284S/L293F I91F/T83N M160H/L242I

G181S/S353K T65A/S353E L284S/L293S I91F/Q92R M160H/Q108H

G181S/A256D T65A/S353K L284S/L66F I91F/F267I M160H/F68V

G181S/A256E T65A/A256D L284S/C282D I91F/F267Q M160H/G100S

G181S/R224L T65A/A256E L284S/A222H I91F/E4K M160H/G100T

G181S/A134M T65A/R224L L284S/A222L I91F/E90D M160H/L323I

G181S/V359E T65A/A134M L284S/E356S I91F/T312K M160H/L323M

G181S/V359K T65A/V359E L284S/S109G I91F/T312N M160H/Q277D

G181S/S333A T65A/V359K L284S/I290L I91F/L241V M160H/Q277E

G181S/S333E T65A/S333A L284S/I290M I91F/V255I M160H/C269N

G181S/T352D T65A/S333E L284S/L330M I91F/F344G M160H/C269T

G181S/T352E T65A/T352D L284S/H131C I91F/I76L M160H/A326F

G181S/M157F T65A/T352E L284S/A189G I91F/I76M M160H/A326I

G181S/M157S T65A/M157F L284S/Q193K I91F/G138K M160H/L152F

G181S/D14G T65A/M157S L284S/Q193R I91F/L238F M160H/C282N

G181S/D296A T65A/D14G L284S/L242I I91F/L238T M160H/S329P

G181S/D296L T65A/D296A L284S/Q108H I91F/I35L M160H/I45D

G181S/T314A T65A/D296L L284S/F68V I91F/I35V M160H/I45L

G181S/T314E T65A/T314A L284S/G100S I91F/C208A M160H/E258A

G181S/F267Y T65A/T314E L284S/G100T I91F/C208S M160H/A272E

G181S/E71N T65A/F267Y L284S/L323I I91F/E240A M160H/T312A

G181S/E252Q T65A/E71N L284S/L323M I91F/E240T M160H/T312R

G181S/I367V T65A/E252Q L284S/Q277D I91F/N148H M160H/M327Q

G181S/A31M T65A/I367V L284S/Q277E I91F/F94L M160H/M327T

G181S/A31S T65A/A31M L284S/C269N I91F/F94Y M160H/N174Y

G181S/F93A T65A/A31S L284S/C269T I91F/V150L M160H/L340I

G181S/L323C T65A/F93A L284S/A326F I91F/F68P M160H/L340M

G181S/L323V T65A/L323C L284S/A326I I91F/N148R M160H/A189H

G181S/T83G T65A/L323V L284S/L152F I91F/K361R M160H/A189Y

G181S/T83N T65A/T83G L284S/C282N I91F/Q280E M160H/N194R

G181S/Q92R T65A/T83N L284S/S329P I91F/Q280R M160H/N194S

G181S/F267I T65A/Q92R L284S/I45D I91F/K225E M160H/L169V

G181S/F267Q T65A/F267I L284S/I45L I91F/K225G M160H/K225D

G181S/E4K T65A/F267Q L284S/E258A I91F/L238A M160H/K225S

G181S/E90D T65A/E4K L284S/A272E I91F/L238S M160H/A63I

G181S/T312K T65A/E90D L284S/T312A I91F/C269A M160H/A63P

G181S/T312N T65A/T312K L284S/T312R I91F/C269I M160H/I180L

G181S/L241V T65A/T312N L284S/M327Q I91F/D296P M160H/I180V

G181S/V255I T65A/L241V L284S/M327T I91F/F140Y M160H/H151D

G181S/F344G T65A/V255I L284S/N174Y I91F/I24L M160H/T220I

G181S/I76L T65A/F344G L284S/L340I I91F/I24V M160H/T220S Positions Positions Positions Positions Positions

G181S/I76M T65A/I76L L284S/L340M I91F/D170S M160H/L246I

G181S/G138K T65A/I76M L284S/A189H I91F/V229M M160H/A272P

G181S/L238F T65A/G138K L284S/A189Y I91F/E360A M160H/S353E

G181S/L238T T65A/L238F L284S/N194R I91F/S322V M160H/S353K

G181S/I35L T65A/L238T L284S/N194S I91F/F347I M160H/A256D

G181S/I35V T65A/I35L L284S/L169V I91F/V221F M160H/A256E

G181S/C208A T65A/I35V L284S/K225D I91F/V221I M160H/R224L

G181S/C208S T65A/C208A L284S/K225S I91F/G245S M160H/A134M

G181S/E240A T65A/C208S L284S/A63I I91F/Q92C M160H/V359E

G181S/E240T T65A/E240A L284S/A63P I91F/Q92S M160H/V359K

G181S/N148H T65A/E240T L284S/I180L I91F/F230A M160H/S333A

G181S/F94L T65A/N148H L284S/I180V I91F/F230N M160H/S333E

G181S/F94Y T65A/F94L L284S/H151D I91F/S87P M160H/T352D

G181S/V150L T65A/F94Y L284S/T220I I91F/S87Q M160H/T352E

G181S/F68P T65A/V150L L284S/T220S I91F/L98H M160H/M157F

G181S/N148R T65A/F68P L284S/L246I I91F/S70K M160H/M157S

G181S/K361R T65A/N148R L284S/A272P I91F/F351A M160H/D14G

G181S/Q280E T65A/K361R L284S/S353E I91F/F351V M160H/D296A

G181S/Q280R T65A/Q280E L284S/S353K I91F/M157Y M160H/D296L

G181S/K225E T65A/Q280R L284S/A256D I91F/C44F M160H/T314A

G181S/K225G T65A/K225E L284S/A256E I91F/C44Y M160H/T314E

G181S/L238A T65A/K225G L284S/R224L I91F/I3L M160H/F267Y

G181S/L238S T65A/L238A L284S/A134M I91F/I3M M160H/E71N

G181S/C269A T65A/L238S L284S/V359E E360G/E360L M160H/E252Q

G181S/C269I T65A/C269A L284S/V359K E360G/A315R M160H/I367V

G181S/D296P T65A/C269I L284S/S333A E360G/A315S M160H/A31M

G181S/F140Y T65A/D296P L284S/S333E E360G/C282S M160H/A31S

G181S/I24L T65A/F140Y L284S/T352D E360G/C282V M160H/F93A

G181S/I24V T65A/I24L L284S/T352E E360G/G135A M160H/L323C

G181S/D170S T65A/I24V L284S/M157F E360G/V221C M160H/L323V

G181S/V229M T65A/D170S L284S/M157S E360G/V221M M160H/T83G

G181S/E360A T65A/V229M L284S/D14G E360G/R247M M160H/T83N

G181S/S322V T65A/E360A L284S/D296A E360G/R247N M160H/Q92R

G181S/F347I T65A/S322V L284S/D296L E360G/I91L M160H/F267I

G181S/V221F T65A/F347I L284S/T314A E360G/I91V M160H/F267Q

G181S/V221I T65A/V221F L284S/T314E E360G/M160H M160H/E4K

G181S/G245S T65A/V221I L284S/F267Y E360G/L293F M160H/E90D

G181S/Q92C T65A/G245S L284S/E71N E360G/L293S M160H/T312K

G181S/Q92S T65A/Q92C L284S/E252Q E360G/L66F M160H/T312N

G181S/F230A T65A/Q92S L284S/I367V E360G/C282D M160H/L241V

G181S/F230N T65A/F230A L284S/A31M E360G/A222H M160H/V255I

G181S/S87P T65A/F230N L284S/A31S E360G/A222L M160H/F344G Positions Positions Positions Positions Positions

G181S/S87Q T65A/S87P L284S/F93A E360G/E356S M160H/I76L

G181S/L98H T65A/S87Q L284S/L323C E360G/S109G M160H/I76M

G181S/S70K T65A/L98H L284S/L323V E360G/I290L M160H/G138K

G181S/F351A T65A/S70K L284S/T83G E360G/I290M M160H/L238F

G181S/F351V T65A/F351A L284S/T83N E360G/L330M M160H/L238T

G181S/M157Y T65A/F351V L284S/Q92R E360G/H131C M160H/I35L

G181S/C44F T65A/M157Y L284S/F267I E360G/A189G M160H/I35V

G181S/C44Y T65A/C44F L284S/F267Q E360G/Q193K M160H/C208A

G181S/I3L T65A/C44Y L284S/E4K E360G/Q193R M160H/C208S

G181S/I3M T65A/I3L L284S/E90D E360G/L242I M160H/E240A

E111P/E111S T65A/I3M L284S/T312K E360G/Q108H M160H/E240T

E111P/F344Y I106V/P186Q L284S/T312N E360G/F68V M160H/N148H

E111P/V165A I106V/M319I L284S/L241V E360G/G100S M160H/F94L

E111P/V218F I106V/M319V L284S/V255I E360G/G100T M160H/F94Y

E111P/N96S I106V/G245A L284S/F344G E360G/L323I M160H/V150L

E111P/F347Y I106V/G245C L284S/I76L E360G/L323M M160H/F68P

E111P/M206C I106V/C282E L284S/I76M E360G/Q277D M160H/N148R

E111P/M206L I106V/C282I L284S/G138K E360G/Q277E M160H/K361R

E111P/P129V I106V/F335L L284S/L238F E360G/C269N M160H/Q280E

E111P/T65A I106V/T248A L284S/L238T E360G/C269T M160H/Q280R

E111P/I106V I106V/T248D L284S/I35L E360G/A326F M160H/K225E

E111P/P186Q I106V/L284S L284S/I35V E360G/A326I M160H/K225G

E111P/M319I I106V/N350K L284S/C208A E360G/L152F M160H/L238A

E111P/M319V I106V/N350R L284S/C208S E360G/C282N M160H/L238S

E111P/G245A I106V/F132L L284S/E240A E360G/S329P M160H/C269A

E111P/G245C I106V/I287L L284S/E240T E360G/I45D M160H/C269I

E111P/C282E I106V/V36I L284S/N148H E360G/I45L M160H/D296P

E111P/C282I I106V/V36L L284S/F94L E360G/E258A M160H/F140Y

E111P/F335L I106V/H131V L284S/F94Y E360G/A272E M160H/I24L

E111P/T248A I106V/H131Y L284S/V150L E360G/T312A M160H/I24V

E111P/T248D I106V/S243E L284S/F68P E360G/T312R M160H/D170S

E111P/L284S I106V/I211L L284S/N148R E360G/M327Q M160H/V229M

E111P/N350K I106V/I211V L284S/K361R E360G/M327T M160H/E360A

E111P/N350R I106V/I91F L284S/Q280E E360G/N174Y M160H/S322V

E111P/F132L I106V/E360G L284S/Q280R E360G/L340I M160H/F347I

E111P/I287L I106V/E360L L284S/K225E E360G/L340M M160H/V221F

E111P/V36I I106V/A315R L284S/K225G E360G/A189H M160H/V221I

E111P/V36L I106V/A315S L284S/L238A E360G/A189Y M160H/G245S

E111P/H131V I106V/C282S L284S/L238S E360G/N194R M160H/Q92C

E111P/H131Y I106V/C282V L284S/C269A E360G/N194S M160H/Q92S

E111P/S243E I106V/G135A L284S/C269I E360G/L169V M160H/F230A

E111P/I211L I106V/V221C L284S/D296P E360G/K225D M160H/F230N Positions Positions Positions Positions Positions

E111P/I211V I106V/V221M L284S/F140Y E360G/K225S M160H/S87P

E111P/I91F I106V/R247M L284S/I24L E360G/A63I M160H/S87Q

E111P/E360G I106V/R247N L284S/I24V E360G/A63P M160H/L98H

E111P/E360L I106V/I91L L284S/D170S E360G/I180L M160H/S70K

E111P/A315R I106V/I91V L284S/V229M E360G/I180V M160H/F351A

E111P/A315S I106V/M160H L284S/E360A E360G/H151D M160H/F351V

E111P/C282S I106V/L293F L284S/S322V E360G/T220I M160H/M157Y

E111P/C282V I106V/L293S L284S/F347I E360G/T220S M160H/C44F

E111P/G135A I106V/L66F L284S/V221F E360G/L246I M160H/C44Y

E111P/V221C I106V/C282D L284S/V221I E360G/A272P M160H/I3L

E111P/V221M I106V/A222H L284S/G245S E360G/S353E M160H/I3M

E111P/R247M I106V/A222L L284S/Q92C E360G/S353K L293F/L293S

E111P/R247N I106V/E356S L284S/Q92S E360G/A256D L293F/L66F

E111P/I91L I106V/S109G L284S/F230A E360G/A256E L293F/C282D

E111P/I91V I106V/I290L L284S/F230N E360G/R224L L293F/A222H

E111P/M160H I106V/I290M L284S/S87P E360G/A134M L293F/A222L

E111P/L293F I106V/L330M L284S/S87Q E360G/V359E L293F/E356S

E111P/L293S I106V/H131C L284S/L98H E360G/V359K L293F/S109G

E111P/L66F I106V/A189G L284S/S70K E360G/S333A L293F/I290L

E111P/C282D I106V/Q193K L284S/F351A E360G/S333E L293F/I290M

E111P/A222H I106V/Q193R L284S/F351V E360G/T352D L293F/L330M

E111P/A222L I106V/L242I L284S/M157Y E360G/T352E L293F/H131C

E111P/E356S I106V/Q108H L284S/C44F E360G/M157F L293F/A189G

E111P/S109G I106V/F68V L284S/C44Y E360G/M157S L293F/Q193K

E111P/I290L I106V/G100S L284S/I3L E360G/D14G L293F/Q193R

E111P/I290M I106V/G100T L284S/I3M E360G/D296A L293F/L242I

E111P/L330M I106V/L323I N350K/N350R E360G/D296L L293F/Q108H

E111P/H131C I106V/L323M N350K/F132L E360G/T314A L293F/F68V

E111P/A189G I106V/Q277D N350K/I287L E360G/T314E L293F/G100S

E111P/Q193K I106V/Q277E N350K/V36I E360G/F267Y L293F/G100T

E111P/Q193R I106V/C269N N350K/V36L E360G/E71N L293F/L323I

E111P/L242I I106V/C269T N350K/H131V E360G/E252Q L293F/L323M

E111P/Q108H I106V/A326F N350K/H131Y E360G/I367V L293F/Q277D

E111P/F68V I106V/A326I N350K/S243E E360G/A31M L293F/Q277E

E111P/G100S I106V/L152F N350K/I211L E360G/A31S L293F/C269N

E111P/G100T I106V/C282N N350K/I211V E360G/F93A L293F/C269T

E111P/L323I I106V/S329P N350K/I91F E360G/L323C L293F/A326F

E111P/L323M I106V/I45D N350K/E360G E360G/L323V L293F/A326I

E111P/Q277D I106V/I45L N350K/E360L E360G/T83G L293F/L152F

E111P/Q277E I106V/E258A N350K/A315R E360G/T83N L293F/C282N

E111P/C269N I106V/A272E N350K/A315S E360G/Q92R L293F/S329P

E111P/C269T I106V/T312A N350K/C282S E360G/F267I L293F/I45D Positions Positions Positions Positions Positions

E111P/A326F I106V/T312R N350K/C282V E360G/F267Q L293F/I45L

E111P/A326I I106V/M327Q N350K/G135A E360G/E4K L293F/E258A

E111P/L152F I106V/M327T N350K/V221C E360G/E90D L293F/A272E

E111P/C282N I106V/N174Y N350K/V221M E360G/T312K L293F/T312A

E111P/S329P I106V/L340I N350K/R247M E360G/T312N L293F/T312R

E111P/I45D I106V/L340M N350K/R247N E360G/L241V L293F/M327Q

E111P/I45L I106V/A189H N350K/I91L E360G/V255I L293F/M327T

E111P/E258A I106V/A189Y N350K/I91V E360G/F344G L293F/N174Y

E111P/A272E I106V/N194R N350K/M160H E360G/I76L L293F/L340I

E111P/T312A I106V/N194S N350K/L293F E360G/I76M L293F/L340M

E111P/T312R I106V/L169V N350K/L293S E360G/G138K L293F/A189H

E111P/M327Q I106V/K225D N350K/L66F E360G/L238F L293F/A189Y

E111P/M327T I106V/K225S N350K/C282D E360G/L238T L293F/N194R

E111P/N174Y I106V/A63I N350K/A222H E360G/I35L L293F/N194S

E111P/L340I I106V/A63P N350K/A222L E360G/I35V L293F/L169V

E111P/L340M I106V/I180L N350K/E356S E360G/C208A L293F/K225D

E111P/A189H I106V/I180V N350K/S109G E360G/C208S L293F/K225S

E111P/A189Y I106V/H151D N350K/I290L E360G/E240A L293F/A63I

E111P/N194R I106V/T220I N350K/I290M E360G/E240T L293F/A63P

E111P/N194S I106V/T220S N350K/L330M E360G/N148H L293F/I180L

E111P/L169V I106V/L246I N350K/H131C E360G/F94L L293F/I180V

E111P/K225D I106V/A272P N350K/A189G E360G/F94Y L293F/H151D

E111P/K225S I106V/S353E N350K/Q193K E360G/V150L L293F/T220I

E111P/A63I I106V/S353K N350K/Q193R E360G/F68P L293F/T220S

E111P/A63P I106V/A256D N350K/L242I E360G/N148R L293F/L246I

E111P/I180L I106V/A256E N350K/Q108H E360G/K361R L293F/A272P

E111P/I180V I106V/R224L N350K/F68V E360G/Q280E L293F/S353E

E111P/H151D I106V/A134M N350K/G100S E360G/Q280R L293F/S353K

E111P/T220I I106V/V359E N350K/G100T E360G/K225E L293F/A256D

E111P/T220S I106V/V359K N350K/L323I E360G/K225G L293F/A256E

E111P/L246I I106V/S333A N350K/L323M E360G/L238A L293F/R224L

E111P/A272P I106V/S333E N350K/Q277D E360G/L238S L293F/A134M

E111P/S353E I106V/T352D N350K/Q277E E360G/C269A L293F/V359E

E111P/S353K I106V/T352E N350K/C269N E360G/C269I L293F/V359K

E111P/A256D I106V/M157F N350K/C269T E360G/D296P L293F/S333A

E111P/A256E I106V/M157S N350K/A326F E360G/F140Y L293F/S333E

E111P/R224L I106V/D14G N350K/A326I E360G/I24L L293F/T352D

E111P/A134M I106V/D296A N350K/L152F E360G/I24V L293F/T352E

E111P/V359E I106V/D296L N350K/C282N E360G/D170S L293F/M157F

E111P/V359K I106V/T314A N350K/S329P E360G/V229M L293F/M157S

E111P/S333A I106V/T314E N350K/I45D E360G/E360A L293F/D14G

E111P/S333E I106V/F267Y N350K/I45L E360G/S322V L293F/D296A Positions Positions Positions Positions Positions

E111P/T352D I106V/E71N N350K/E258A E360G/F347I L293F/D296L

E111P/T352E I106V/E252Q N350K/A272E E360G/V221F L293F/T314A

E111P/M157F 1106V/ 1367V N350K/T312A E360G/V221I L293F/T314E

E111P/M157S I106V/A31M N350K/T312R E360G/G245S L293F/F267Y

E111P/D14G I106V/A31S N350K/M327Q E360G/Q92C L293F/E71N

E111P/D296A I106V/F93A N350K/M327T E360G/Q92S L293F/E252Q

E111P/D296L I106V/L323C N350K/N174Y E360G/F230A L293F/I367V

E111P/T314A I106V/L323V N350K/L340I E360G/F230N L293F/A31M

E111P/T314E I106V/T83G N350K/L340M E360G/S87P L293F/A31S

E111P/F267Y I106V/T83N N350K/A189H E360G/S87Q L293F/F93A

E111P/E71N I106V/Q92R N350K/A189Y E360G/L98H L293F/L323C

E111P/E252Q I106V/F267I N350K/N194R E360G/S70K L293F/L323V

E111P/I367V I106V/F267Q N350K/N194S E360G/F351A L293F/T83G

E111P/A31M I106V/E4K N350K/L169V E360G/F351V L293F/T83N

E111P/A31S I106V/E90D N350K/K225D E360G/M157Y L293F/Q92R

E111P/F93A I106V/T312K N350K/K225S E360G/C44F L293F/F267I

E111P/L323C I106V/T312N N350K/A63I E360G/C44Y L293F/F267Q

E111P/L323V I106V/L241V N350K/A63P E360G/I3L L293F/E4K

E111P/T83G I106V/V255I N350K/I180L E360G/I3M L293F/E90D

E111P/T83N I106V/F344G N350K/I180V E360L/A315R L293F/T312K

E111P/Q92R I106V/I76L N350K/H151D E360L/A315S L293F/T312N

E111P/F267I I106V/I76M N350K/T220I E360L/C282S L293F/L241V

E111P/F267Q I106V/G138K N350K/T220S E360L/C282V L293F/V255I

E111P/E4K I106V/L238F N350K/L246I E360L/G135A L293F/F344G

E111P/E90D I106V/L238T N350K/A272P E360L/V221C L293F/I76L

E111P/T312K I106V/I35L N350K/S353E E360L/V221M L293F/I76M

E111P/T312N I106V/I35V N350K/S353K E360L/R247M L293F/G138K

E111P/L241V I106V/C208A N350K/A256D E360L/R247N L293F/L238F

E111P/V255I I106V/C208S N350K/A256E E360L/I91L L293F/L238T

E111P/F344G I106V/E240A N350K/R224L E360L/I91V L293F/I35L

E111P/I76L I106V/E240T N350K/A134M E360L/M160H L293F/I35V

E111P/I76M I106V/N148H N350K/V359E E360L/L293F L293F/C208A

E111P/G138K I106V/F94L N350K/V359K E360L/L293S L293F/C208S

E111P/L238F I106V/F94Y N350K/S333A E360L/L66F L293F/E240A

E111P/L238T I106V/V150L N350K/S333E E360L/C282D L293F/E240T

E111P/I35L I106V/F68P N350K/T352D E360L/A222H L293F/N148H

E111P/I35V I106V/N148R N350K/T352E E360L/A222L L293F/F94L

E111P/C208A I106V/K361R N350K/M157F E360L/E356S L293F/F94Y

E111P/C208S I106V/Q280E N350K/M157S E360L/S109G L293F/V150L

E111P/E240A I106V/Q280R N350K/D14G E360L/I290L L293F/F68P

E111P/E240T I106V/K225E N350K/D296A E360L/I290M L293F/N148R

E111P/N148H I106V/K225G N350K/D296L E360L/L330M L293F/K361R Positions Positions Positions Positions Positions

E111P/F94L I106V/L238A N350K/T314A E360L/H131C L293F/Q280E

E111P/F94Y I106V/L238S N350K/T314E E360L/A189G L293F/Q280R

E111P/V150L I106V/C269A N350K/F267Y E360L/Q193K L293F/K225E

E111P/F68P I106V/C269I N350K/E71N E360L/Q193R L293F/K225G

E111P/N148R I106V/D296P N350K/E252Q E360L/L242I L293F/L238A

E111P/K361R I106V/F140Y N350K/I367V E360L/Q108H L293F/L238S

E111P/Q280E I106V/I24L N350K/A31M E360L/F68V L293F/C269A

E111P/Q280R I106V/I24V N350K/A31S E360L/G100S L293F/C269I

E111P/K225E I106V/D170S N350K/F93A E360L/G100T L293F/D296P

E111P/K225G I106V/V229M N350K/L323C E360L/L323I L293F/F140Y

E111P/L238A I106V/E360A N350K/L323V E360L/L323M L293F/I24L

E111P/L238S I106V/S322V N350K/T83G E360L/Q277D L293F/I24V

E111P/C269A I106V/F347I N350K/T83N E360L/Q277E L293F/D170S

E111P/C269I I106V/V221F N350K/Q92R E360L/C269N L293F/V229M

E111P/D296P I106V/V221I N350K/F267I E360L/C269T L293F/E360A

E111P/F140Y I106V/G245S N350K/F267Q E360L/A326F L293F/S322V

E111P/I24L I106V/Q92C N350K/E4K E360L/A326I L293F/F347I

E111P/I24V I106V/Q92S N350K/E90D E360L/L152F L293F/V221F

E111P/D170S I106V/F230A N350K/T312K E360L/C282N L293F/V221I

E111P/V229M I106V/F230N N350K/T312N E360L/S329P L293F/G245S

E111P/E360A I106V/S87P N350K/L241V E360L/I45D L293F/Q92C

E111P/S322V I106V/S87Q N350K/V255I E360L/I45L L293F/Q92S

E111P/F347I I106V/L98H N350K/F344G E360L/E258A L293F/F230A

E111P/V221F I106V/S70K N350K/I76L E360L/A272E L293F/F230N

E111P/V221I I106V/F351A N350K/I76M E360L/T312A L293F/S87P

E111P/G245S I106V/F351V N350K/G138K E360L/T312R L293F/S87Q

E111P/Q92C I106V/M157Y N350K/L238F E360L/M327Q L293F/L98H

E111P/Q92S I106V/C44F N350K/L238T E360L/M327T L293F/S70K

E111P/F230A I106V/C44Y N350K/I35L E360L/N174Y L293F/F351A

E111P/F230N I106V/I3L N350K/I35V E360L/L340I L293F/F351V

E111P/S87P I106V/I3M N350K/C208A E360L/L340M L293F/M157Y

E111P/S87Q P186Q/M319I N350K/C208S E360L/A189H L293F/C44F

E111P/L98H P186Q/M319V N350K/E240A E360L/A189Y L293F/C44Y

E111P/S70K P186Q/G245A N350K/E240T E360L/N194R L293F/I3L

E111P/F351A P186Q/G245C N350K/N148H E360L/N194S L293F/I3M

E111P/F351V P186Q/C282E N350K/F94L E360L/L169V L293S/L66F

E111P/M157Y P186Q/C282I N350K/F94Y E360L/K225D L293S/C282D

E111P/C44F P186Q/F335L N350K/V150L E360L/K225S L293S/A222H

E111P/C44Y P186Q/T248A N350K/F68P E360L/A63I L293S/A222L

E111P/I3L P186Q/T248D N350K/N148R E360L/A63P L293S/E356S

E111P/I3M P186Q/L284S N350K/K361R E360L/I180L L293S/S109G

E111S/F344Y P186Q/N350K N350K/Q280E E360L/I180V L293S/I290L Positions Positions Positions Positions Positions

E111S/V165A P186Q/N350R N350K/Q280R E360L/H151D L293S/I290M

E111S/V218F P186Q/F132L N350K/K225E E360L/T220I L293S/L330M

E111S/N96S P186Q/I287L N350K/K225G E360L/T220S L293S/H131C

E111S/F347Y P186Q/V36I N350K/L238A E360L/L246I L293S/A189G

E111S/M206C P186Q/V36L N350K/L238S E360L/A272P L293S/Q193K

E111S/M206L P186Q/H131V N350K/C269A E360L/S353E L293S/Q193R

E111S/P129V P186Q/H131Y N350K/C269I E360L/S353K L293S/L242I

E111S/T65A P186Q/S243E N350K/D296P E360L/A256D L293S/Q108H

E111S/I106V P186Q/I211L N350K/F140Y E360L/A256E L293S/F68V

E111S/P186Q P186Q/I211V N350K/I24L E360L/R224L L293S/G100S

E111S/M319I P186Q/I91F N350K/I24V E360L/A134M L293S/G100T

E111S/M319V P186Q/E360G N350K/D170S E360L/V359E L293S/L323I

E111S/G245A P186Q/E360L N350K/V229M E360L/V359K L293S/L323M

E111S/G245C P186Q/A315R N350K/E360A E360L/S333A L293S/Q277D

E111S/C282E P186Q/A315S N350K/S322V E360L/S333E L293S/Q277E

E111S/C282I P186Q/C282S N350K/F347I E360L/T352D L293S/C269N

E111S/F335L P186Q/C282V N350K/V221F E360L/T352E L293S/C269T

E111S/T248A P186Q/G135A N350K/V221I E360L/M157F L293S/A326F

E111S/T248D P186Q/V221C N350K/G245S E360L/M157S L293S/A326I

E111S/L284S P186Q/V221M N350K/Q92C E360L/D14G L293S/L152F

E111S/N350K P186Q/R247M N350K/Q92S E360L/D296A L293S/C282N

E111S/N350R P186Q/R247N N350K/F230A E360L/D296L L293S/S329P

E111S/F132L P186Q/I91L N350K/F230N E360L/T314A L293S/I45D

E111S/I287L P186Q/I91V N350K/S87P E360L/T314E L293S/I45L

E111S/V36I P186Q/M160H N350K/S87Q E360L/F267Y L293S/E258A

E111S/V36L P186Q/L293F N350K/L98H E360L/E71N L293S/A272E

E111S/H131V P186Q/L293S N350K/S70K E360L/E252Q L293S/T312A

E111S/H131Y P186Q/L66F N350K/F351A E360L/I367V L293S/T312R

E111S/S243E P186Q/C282D N350K/F351V E360L/A31M L293S/M327Q

E111S/I211L P186Q/A222H N350K/M157Y E360L/A31S L293S/M327T

E111S/I211V P186Q/A222L N350K/C44F E360L/F93A L293S/N174Y

E111S/I91F P186Q/E356S N350K/C44Y E360L/L323C L293S/L340I

E111S/E360G P186Q/S109G N350K/I3L E360L/L323V L293S/L340M

E111S/E360L P186Q/I290L N350K/I3M E360L/T83G L293S/A189H

E111S/A315R P186Q/I290M N350R/F132L E360L/T83N L293S/A189Y

E111S/A315S P186Q/L330M N350R/I287L E360L/Q92R L293S/N194R

E111S/C282S P186Q/H131C N350R/V36I E360L/F267I L293S/N194S

E111S/C282V P186Q/A189G N350R/V36L E360L/F267Q L293S/L169V

E111S/G135A P186Q/Q193K N350R/H131V E360L/E4K L293S/K225D

E111S/V221C P186Q/Q193R N350R/H131Y E360L/E90D L293S/K225S

E111S/V221M P186Q/L242I N350R/S243E E360L/T312K L293S/A63I

E111S/R247M P186Q/Q108H N350R/I211L E360L/T312N L293S/A63P Positions Positions Positions Positions Positions

E111S/R247N P186Q/F68V N350R/I211V E360L/L241V L293S/I180L

E111S/I91L P186Q/G100S N350R/I91F E360L/V255I L293S/I180V

E111S/I91V P186Q/G100T N350R/E360G E360L/F344G L293S/H151D

E111S/M160H P186Q/L323I N350R/E360L E360L/I76L L293S/T220I

E111S/L293F P186Q/L323M N350R/A315R E360L/I76M L293S/T220S

E111S/L293S P186Q/Q277D N350R/A315S E360L/G138K L293S/L246I

E111S/L66F P186Q/Q277E N350R/C282S E360L/L238F L293S/A272P

E111S/C282D P186Q/C269N N350R/C282V E360L/L238T L293S/S353E

E111S/A222H P186Q/C269T N350R/G135A E360L/I35L L293S/S353K

E111S/A222L P186Q/A326F N350R/V221C E360L/I35V L293S/A256D

E111S/E356S P186Q/A326I N350R/V221M E360L/C208A L293S/A256E

E111S/S109G P186Q/L152F N350R/R247M E360L/C208S L293S/R224L

E111S/I290L P186Q/C282N N350R/R247N E360L/E240A L293S/A134M

E111S/I290M P186Q/S329P N350R/I91L E360L/E240T L293S/V359E

E111S/L330M P186Q/I45D N350R/I91V E360L/N148H L293S/V359K

E111S/H131C P186Q/I45L N350R/M160H E360L/F94L L293S/S333A

E111S/A189G P186Q/E258A N350R/L293F E360L/F94Y L293S/S333E

E111S/Q193K P186Q/A272E N350R/L293S E360L/V150L L293S/T352D

E111S/Q193R P186Q/T312A N350R/L66F E360L/F68P L293S/T352E

E111S/L242I P186Q/T312R N350R/C282D E360L/N148R L293S/M157F

E111S/Q108H P186Q/M327Q N350R/A222H E360L/K361R L293S/M157S

E111S/F68V P186Q/M327T N350R/A222L E360L/Q280E L293S/D14G

E111S/G100S P186Q/N174Y N350R/E356S E360L/Q280R L293S/D296A

E111S/G100T P186Q/L340I N350R/S109G E360L/K225E L293S/D296L

E111S/L323I P186Q/L340M N350R/I290L E360L/K225G L293S/T314A

E111S/L323M P186Q/A189H N350R/I290M E360L/L238A L293S/T314E

E111S/Q277D P186Q/A189Y N350R/L330M E360L/L238S L293S/F267Y

E111S/Q277E P186Q/N194R N350R/H131C E360L/C269A L293S/E71N

E111S/C269N P186Q/N194S N350R/A189G E360L/C269I L293S/E252Q

E111S/C269T P186Q/L169V N350R/Q193K E360L/D296P L293S/I367V

E111S/A326F P186Q/K225D N350R/Q193R E360L/F140Y L293S/A31M

E111S/A326I P186Q/K225S N350R/L242I E360L/I24L L293S/A31S

E111S/L152F P186Q/A63I N350R/Q108H E360L/I24V L293S/F93A

E111S/C282N P186Q/A63P N350R/F68V E360L/D170S L293S/L323C

E111S/S329P P186Q/I180L N350R/G100S E360L/V229M L293S/L323V

E111S/I45D P186Q/I180V N350R/G100T E360L/E360A L293S/T83G

E111S/I45L P186Q/H151D N350R/L323I E360L/S322V L293S/T83N

E111S/E258A P186Q/T220I N350R/L323M E360L/F347I L293S/Q92R

E111S/A272E P186Q/T220S N350R/Q277D E360L/V221F L293S/F267I

E111S/T312A P186Q/L246I N350R/Q277E E360L/V221I L293S/F267Q

E111S/T312R P186Q/A272P N350R/C269N E360L/G245S L293S/E4K

E111S/M327Q P186Q/S353E N350R/C269T E360L/Q92C L293S/E90D Positions Positions Positions Positions Positions

E111S/M327T P186Q/S353K N350R/A326F E360L/Q92S L293S/T312K

E111S/N174Y P186Q/A256D N350R/A326I E360L/F230A L293S/T312N

E111S/L340I P186Q/A256E N350R/L152F E360L/F230N L293S/L241V

E111S/L340M P186Q/R224L N350R/C282N E360L/S87P L293S/V255I

E111S/A189H P186Q/A134M N350R/S329P E360L/S87Q L293S/F344G

E111S/A189Y P186Q/V359E N350R/I45D E360L/L98H L293S/I76L

E111S/N194R P186Q/V359K N350R/I45L E360L/S70K L293S/I76M

E111S/N194S P186Q/S333A N350R/E258A E360L/F351A L293S/G138K

E111S/L169V P186Q/S333E N350R/A272E E360L/F351V L293S/L238F

E111S/K225D P186Q/T352D N350R/T312A E360L/M157Y L293S/L238T

E111S/K225S P186Q/T352E N350R/T312R E360L/C44F L293S/I35L

E111S/A63I P186Q/M157F N350R/M327Q E360L/C44Y L293S/I35V

E111S/A63P P186Q/M157S N350R/M327T E360L/I3L L293S/C208A

E111S/I180L P186Q/D14G N350R/N174Y E360L/I3M L293S/C208S

E111S/I180V P186Q/D296A N350R/L340I A315R/A315S L293S/E240A

E111S/H151D P186Q/D296L N350R/L340M A315R/C282S L293S/E240T

E111S/T220I P186Q/T314A N350R/A189H A315R/C282V L293S/N148H

E111S/T220S P186Q/T314E N350R/A189Y A315R/G135A L293S/F94L

E111S/L246I P186Q/F267Y N350R/N194R A315R/V221C L293S/F94Y

E111S/A272P P186Q/E71N N350R/N194S A315R/V221M L293S/V150L

E111S/S353E P186Q/E252Q N350R/L169V A315R/R247M L293S/F68P

E111S/S353K P186Q/I367V N350R/K225D A315R/R247N L293S/N148R

E111S/A256D P186Q/A31M N350R/K225S A315R/I91L L293S/K361R

E111S/A256E P186Q/A31S N350R/A63I A315R/I91V L293S/Q280E

E111S/R224L P186Q/F93A N350R/A63P A315R/M160H L293S/Q280R

E111S/A134M P186Q/L323C N350R/I180L A315R/L293F L293S/K225E

E111S/V359E P186Q/L323V N350R/I180V A315R/L293S L293S/K225G

E111S/V359K P186Q/T83G N350R/H151D A315R/L66F L293S/L238A

E111S/S333A P186Q/T83N N350R/T220I A315R/C282D L293S/L238S

E111S/S333E P186Q/Q92R N350R/T220S A315R/A222H L293S/C269A

E111S/T352D P186Q/F267I N350R/L246I A315R/A222L L293S/C269I

E111S/T352E P186Q/F267Q N350R/A272P A315R/E356S L293S/D296P

E111S/M157F P186Q/E4K N350R/S353E A315R/S109G L293S/F140Y

E111S/M157S P186Q/E90D N350R/S353K A315R/I290L L293S/I24L

E111S/D14G P186Q/T312K N350R/A256D A315R/I290M L293S/I24V

E111S/D296A P186Q/T312N N350R/A256E A315R/L330M L293S/D170S

E111S/D296L P186Q/L241V N350R/R224L A315R/H131C L293S/V229M

E111S/T314A P186Q/V255I N350R/A134M A315R/A189G L293S/E360A

E111S/T314E P186Q/F344G N350R/V359E A315R/Q193K L293S/S322V

E111S/F267Y P186Q/I76L N350R/V359K A315R/Q193R L293S/F347I

E111S/E71N P186Q/I76M N350R/S333A A315R/L242I L293S/V221F

E111S/E252Q P186Q/G138K N350R/S333E A315R/Q108H L293S/V221I Positions Positions Positions Positions Positions

E111S/I367V P186Q/L238F N350R/T352D A315R/F68V L293S/G245S

E111S/A31M P186Q/L238T N350R/T352E A315R/G100S L293S/Q92C

E111S/A31S P186Q/I35L N350R/M157F A315R/G100T L293S/Q92S

E111S/F93A P186Q/I35V N350R/M157S A315R/L323I L293S/F230A

E111S/L323C P186Q/C208A N350R/D14G A315R/L323M L293S/F230N

E111S/L323V P186Q/C208S N350R/D296A A315R/Q277D L293S/S87P

E111S/T83G P186Q/E240A N350R/D296L A315R/Q277E L293S/S87Q

E111S/T83N P186Q/E240T N350R/T314A A315R/C269N L293S/L98H

E111S/Q92R P186Q/N148H N350R/T314E A315R/C269T L293S/S70K

E111S/F267I P186Q/F94L N350R/F267Y A315R/A326F L293S/F351A

E111S/F267Q P186Q/F94Y N350R/E71N A315R/A326I L293S/F351V

E111S/E4K P186Q/V150L N350R/E252Q A315R/L152F L293S/M157Y

E111S/E90D P186Q/F68P N350R/I367V A315R/C282N L293S/C44F

E111S/T312K P186Q/N148R N350R/A31M A315R/S329P L293S/C44Y

E111S/T312N P186Q/K361R N350R/A31S A315R/I45D L293S/I3L

E111S/L241V P186Q/Q280E N350R/F93A A315R/I45L L293S/I3M

E111S/V255I P186Q/Q280R N350R/L323C A315R/E258A L66F/C282D

E111S/F344G P186Q/K225E N350R/L323V A315R/A272E L66F/A222H

E111S/I76L P186Q/K225G N350R/T83G A315R/T312A L66F/A222L

E111S/I76M P186Q/L238A N350R/T83N A315R/T312R L66F/E356S

E111S/G138K P186Q/L238S N350R/Q92R A315R/M327Q L66F/S109G

E111S/L238F P186Q/C269A N350R/F267I A315R/M327T L66F/I290L

E111S/L238T P186Q/C269I N350R/F267Q A315R/N174Y L66F/I290M

E111S/I35L P186Q/D296P N350R/E4K A315R/L340I L66F/L330M

E111S/I35V P186Q/F140Y N350R/E90D A315R/L340M L66F/H131C

E111S/C208A P186Q/I24L N350R/T312K A315R/A189H L66F/A189G

E111S/C208S P186Q/I24V N350R/T312N A315R/A189Y L66F/Q193K

E111S/E240A P186Q/D170S N350R/L241V A315R/N194R L66F/Q193R

E111S/E240T P186Q/V229M N350R/V255I A315R/N194S L66F/L242I

E111S/N148H P186Q/E360A N350R/F344G A315R/L169V L66F/Q108H

E111S/F94L P186Q/S322V N350R/I76L A315R/K225D L66F/F68V

E111S/F94Y P186Q/F347I N350R/I76M A315R/K225S L66F/G100S

E111S/V150L P186Q/V221F N350R/G138K A315R/A63I L66F/G100T

E111S/F68P P186Q/V221I N350R/L238F A315R/A63P L66F/L323I

E111S/N148R P186Q/G245S N350R/L238T A315R/I180L L66F/L323M

E111S/K361R P186Q/Q92C N350R/I35L A315R/I180V L66F/Q277D

E111S/Q280E P186Q/Q92S N350R/I35V A315R/H151D L66F/Q277E

E111S/Q280R P186Q/F230A N350R/C208A A315R/T220I L66F/C269N

E111S/K225E P186Q/F230N N350R/C208S A315R/T220S L66F/C269T

E111S/K225G P186Q/S87P N350R/E240A A315R/L246I L66F/A326F

E111S/L238A P186Q/S87Q N350R/E240T A315R/A272P L66F/A326I

E111S/L238S P186Q/L98H N350R/N148H A315R/S353E L66F/L152F Positions Positions Positions Positions Positions

E111S/C269A P186Q/S70K N350R/F94L A315R/S353K L66F/C282N

E111S/C269I P186Q/F351A N350R/F94Y A315R/A256D L66F/S329P

E111S/D296P P186Q/F351V N350R/V150L A315R/A256E L66F/I45D

E111S/F140Y P186Q/M157Y N350R/F68P A315R/R224L L66F/I45L

E111S/I24L P186Q/C44F N350R/N148R A315R/A134M L66F/E258A

E111S/I24V P186Q/C44Y N350R/K361R A315R/V359E L66F/A272E

E111S/D170S P186Q/I3L N350R/Q280E A315R/V359K L66F/T312A

E111S/V229M P186Q/I3M N350R/Q280R A315R/S333A L66F/T312R

E111S/E360A M319I/M319V N350R/K225E A315R/S333E L66F/M327Q

E111S/S322V M319I/G245A N350R/K225G A315R/T352D L66F/M327T

E111S/F347I M319I/G245C N350R/L238A A315R/T352E L66F/N174Y

E111S/V221F M319I/C282E N350R/L238S A315R/M157F L66F/L340I

E111S/V221I M319I/C282I N350R/C269A A315R/M157S L66F/L340M

E111S/G245S M319I/F335L N350R/C269I A315R/D14G L66F/A189H

E111S/Q92C M319I/T248A N350R/D296P A315R/D296A L66F/A189Y

E111S/Q92S M319I/T248D N350R/F140Y A315R/D296L L66F/N194R

E111S/F230A M319I/L284S N350R/I24L A315R/T314A L66F/N194S

E111S/F230N M319I/N350K N350R/I24V A315R/T314E L66F/L169V

E111S/S87P M319I/N350R N350R/D170S A315R/F267Y L66F/K225D

E111S/S87Q M319I/F132L N350R/V229M A315R/E71N L66F/K225S

E111S/L98H M319I/I287L N350R/E360A A315R/E252Q L66F/A63I

E111S/S70K M319I/V36I N350R/S322V A315R/I367V L66F/A63P

E111S/F351A M319I/V36L N350R/F347I A315R/A31M L66F/I180L

E111S/F351V M319I/H131V N350R/V221F A315R/A31S L66F/I180V

E111S/M157Y M319I/H131Y N350R/V221I A315R/F93A L66F/H151D

E111S/C44F M319I/S243E N350R/G245S A315R/L323C L66F/T220I

E111S/C44Y M319I/I211L N350R/Q92C A315R/L323V L66F/T220S

E111S/I3L M319I/I211V N350R/Q92S A315R/T83G L66F/L246I

E111S/I3M M319I/I91F N350R/F230A A315R/T83N L66F/A272P

F344Y/V165A M319I/E360G N350R/F230N A315R/Q92R L66F/S353E

F344Y/V218F M319I/E360L N350R/S87P A315R/F267I L66F/S353K

F344Y/N96S M319I/A315R N350R/S87Q A315R/F267Q L66F/A256D

F344Y/F347Y M319I/A315S N350R/L98H A315R/E4K L66F/A256E

F344Y/M206C M319I/C282S N350R/S70K A315R/E90D L66F/R224L

F344Y/M206L M319I/C282V N350R/F351A A315R/T312K L66F/A134M

F344Y/P129V M319I/G135A N350R/F351V A315R/T312N L66F/V359E

F344Y/T65A M319I/V221C N350R/M157Y A315R/L241V L66F/V359K

F344Y/I106V M319I/V221M N350R/C44F A315R/V255I L66F/S333A

F344Y/P186Q M319I/R247M N350R/C44Y A315R/F344G L66F/S333E

F344Y/M319I M319I/R247N N350R/I3L A315R/I76L L66F/T352D

F344Y/M319V M319I/I91L N350R/I3M A315R/I76M L66F/T352E

F344Y/G245A M319I/I91V F132L/I287L A315R/G138K L66F/M157F Positions Positions Positions Positions Positions

F344Y/G245C M319I/M160H F132L/V36I A315R/L238F L66F/M157S

F344Y/C282E M319I/L293F F132L/V36L A315R/L238T L66F/D14G

F344Y/C282I M319I/L293S F132L/H131V A315R/I35L L66F/D296A

F344Y/F335L M319I/L66F F132L/H131Y A315R/I35V L66F/D296L

F344Y/T248A M319I/C282D F132L/ S243E A315R/C208A L66F/T314A

F344Y/T248D M319I/A222H F132L/I21 1L A315R/C208S L66F/T314E

F344Y/L284S M319I/A222L F132L/I21 1V A315R/E240A L66F/F267Y

F344Y/N350K M319I/E356S F132L/I91F A315R/E240T L66F/E71N

F344Y/N350R M319I/ S 109G F132L/E360G A315R/N148H L66F/E252Q

F344Y/F132L M319I/I290L F132L/E360L A315R/F94L L66F/I367V

F344Y/I287L M319I/I290M F132L/A315R A315R/F94Y L66F/A31M

F344Y/V36I M319I/L330M F132L/A315S A315R/V150L L66F/A31 S

F344Y/V36L M319I/H131C F132L/C282S A315R/F68P L66F/F93A

F344Y/H131V M319I/A189G F132L/C282V A315R/N148R L66F/L323C

F344Y/H131Y M319I/Q193K F132L/G135A A315R/K361R L66F/L323V

F344Y/ S243E M319I/Q193R F132L/V221C A315R/Q280E L66F/T83G

F344Y/I21 1L M319I/L242I F132L/V221M A315R/Q280R L66F/T83N

F344Y/I21 1V M319I/Q108H F132L/R247M A315R/K225E L66F/Q92R

F344Y/I91F M319I/F68V F132L/R247N A315R/K225G L66F/F267I

F344Y/E360G M319I/G100S F132L/I91L A315R/L238A L66F/F267Q

F344Y/E360L M319I/G100T F132L/I91V A315R/L238S L66F/E4K

F344Y/A315R M319I/L323I F132L/M160H A315R/C269A L66F/E90D

F344Y/A315S M319I/L323M F132L/L293F A315R/C269I L66F/T312K

F344Y/C282S M319I/Q277D F132L/L293S A315R/D296P L66F/T312N

F344Y/C282V M319I/Q277E F132L/L66F A315R/F140Y L66F/L241V

F344Y/G135A M319I/C269N F132L/C282D A315R/I24L L66F/V255I

F344Y/V221C M319I/C269T F132L/A222H A315R/I24V L66F/F344G

F344Y/V221M M319I/A326F F132L/A222L A315R/D170S L66F/I76L

F344Y/R247M M319I/A326I F132L/E356S A315R/V229M L66F/I76M

F344Y/R247N M319I/L152F F132L/ S109G A315R/E360A L66F/G138K

F344Y/I91L M319I/C282N F132L/I290L A315R/ S322V L66F/L238F

F344Y/I91V M319I/ S329P F132L/I290M A315R/F347I L66F/L238T

F344Y/M160H M319I/I45D F132L/L330M A315R/V221F L66F/I35L

F344Y/L293F M319I/I45L F132L/H131C A315R/V221I L66F/I35V

F344Y/L293S M319I/E258A F132L/A189G A315R/G245S L66F/C208A

F344Y/L66F M319I/A272E F132L/Q193K A315R/Q92C L66F/C208S

F344Y/C282D M319I/T312A F132L/Q193R A315R/Q92S L66F/E240A

F344Y/A222H M319I/T312R F132L/L242I A315R/F230A L66F/E240T

F344Y/A222L M319I/M327Q F132L/Q108H A315R/F230N L66F/N148H

F344Y/E356S M319I/M327T F132L/F68V A315R/ S87P L66F/F94L

F344Y/ S109G M319I/N174Y F132L/G100S A315R/ S87Q L66F/F94Y

F344Y/I290L M319I/L340I F132L/G100T A315R/L98H L66F/V150L Positions Positions Positions Positions Positions

F344Y/I290M M319I/L340M F132L/L323I A315R/ S70K L66F/F68P

F344Y/L330M M319I/A189H F132L/L323M A315R/F351A L66F/N148R

F344Y/H131C M319I/A189Y F132L/Q277D A315R/F351V L66F/K361R

F344Y/A189G M319I/N194R F132L/Q277E A315R/M157Y L66F/Q280E

F344Y/Q193K M319I/N194S F132L/C269N A315R/C44F L66F/Q280R

F344Y/Q193R M319I/L169V F132L/C269T A315R/C44Y L66F/K225E

F344Y/L242I M319I/K225D F132L/A326F A315R/I3L L66F/K225G

F344Y/Q108H M319I/K225S F132L/A326I A315R/I3M L66F/L238A

F344Y/F68V M319I/A63I F132L/L152F A315S /C282S L66F/L238S

F344Y/G100S M319I/A63P F132L/C282N A315S /C282V L66F/C269A

F344Y/G100T M319I/I180L F132L/ S329P A315S /G135A L66F/C269I

F344Y/L323I M319I/I180V F132L/I45D A315S /V221C L66F/D296P

F344Y/L323M M319I/H151D F132L/I45L A315S /V221M L66F/F140Y

F344Y/Q277D M319I/T220I F132L/E258A A315S /R247M L66F/I24L

F344Y/Q277E M319I/T220S F132L/A272E A315S /R247N L66F/I24V

F344Y/C269N M319I/L246I F132L/T312A A315S /I91L L66F/D170S

F344Y/C269T M319I/A272P F132L/T312R A315S /I91V L66F/V229M

F344Y/A326F M319I/ S353E F132L/M327Q A315S /M160H L66F/E360A

F344Y/A326I M319I/ S353K F132L/M327T A315S /L293F L66F/ S322V

F344Y/L152F M319I/A256D F132L/N174Y A315S /L293S L66F/F347I

F344Y/C282N M319I/A256E F132L/L340I A315S /L66F L66F/V221F

F344Y/ S329P M319I/R224L F132L/L340M A315S /C282D L66F/V221I

F344Y/I45D M319I/A134M F132L/A189H A315S /A222H L66F/G245S

F344Y/I45L M319I/V359E F132L/A189Y A315S /A222L L66F/Q92C

F344Y/E258A M319I/V359K F132L/N194R A315S /E356S L66F/Q92S

F344Y/A272E M319I/ S333A F132L/N194S A315S / S109G L66F/F230A

F344Y/T312A M319I/ S333E F132L/L169V A315S /I290L L66F/F230N

F344Y/T312R M319I/T352D F132L/K225D A315S /I290M L66F/ S87P

F344Y/M327Q M319I/T352E F132L/K225S A315S /L330M L66F/ S87Q

F344Y/M327T M319I/M157F F132L/A63I A315S /H131C L66F/L98H

F344Y/N174Y M319I/M157S F132L/A63P A315S /A189G L66F/ S70K

F344Y/L340I M319I/D14G F132L/I180L A315S /Q193K L66F/F351A

F344Y/L340M M319I/D296A F132L/I180V A315S /Q193R L66F/F351V

F344Y/A189H M319I/D296L F132L/H151D A315S /L242I L66F/M157Y

F344Y/A189Y M319I/T314A F132L/T220I A315S /Q108H L66F/C44F

F344Y/N194R M319I/T314E F132L/T220S A315S /F68V L66F/C44Y

F344Y/N194S M319I/F267Y F132L/L246I A315S /G100S L66F/I3L

F344Y/L169V M319I/E71N F132L/A272P A315S /G100T L66F/I3M

F344Y/K225D M319I/E252Q F132L/ S353E A315S /L323I C282D /A222H

F344Y/K225S M319I/I367V F132L/ S353K A315S /L323M C282D/A222L

F344Y/A63I M319I/A31M F132L/A256D A315S /Q277D C282D/E356S

F344Y/A63P M319I/A31 S F132L/A256E A315S /Q277E C282D / S109G Positions Positions Positions Positions Positions

F344Y/I180L M319I/F93A F132L/R224L A315S/C269N C282D/I290L

F344Y/I180V M319I/L323C F132L/A134M A315S/C269T C282D/I290M

F344Y/H151D M319I/L323V F132L/V359E A315S/A326F C282D/L330M

F344Y/T220I M319I/T83G F132L/V359K A315S/A326I C282D/H131C

F344Y/T220S M319I/T83N F132L/S333A A315S/L152F C282D/A189G

F344Y/L246I M319I/Q92R F132L/S333E A315S/C282N C282D/Q193K

F344Y/A272P M319I/F267I F132L/T352D A315S/S329P C282D/Q193R

F344Y/S353E M319I/F267Q F132L/T352E A315S/I45D C282D/L242I

F344Y/S353K M319I/E4K F132L/M157F A315S/I45L C282D/Q108H

F344Y/A256D M319I/E90D F132L/M157S A315S/E258A C282D/F68V

F344Y/A256E M319I/T312K F132L/D14G A315S/A272E C282D/G100S

F344Y/R224L M319I/T312N F132L/D296A A315S/T312A C282D/G100T

F344Y/A134M M319I/L241V F132L/D296L A315S/T312R C282D/L323I

F344Y/V359E M319I/V255I F132L/T314A A315S/M327Q C282D/L323M

F344Y/V359K M319I/F344G F132L/T314E A315S/M327T C282D/Q277D

F344Y/S333A M319I/I76L F132L/F267Y A315S/N174Y C282D/Q277E

F344Y/S333E M319I/I76M F132L/E71N A315S/L340I C282D/C269N

F344Y/T352D M319I/G138K F132L/E252Q A315S/L340M C282D/C269T

F344Y/T352E M319I/L238F F132L/I367V A315S/A189H C282D/A326F

F344Y/M157F M319I/L238T F132L/A31M A315S/A189Y C282D/A326I

F344Y/M157S M319I/I35L F132L/A31S A315S/N194R C282D/L152F

F344Y/D14G M319I/I35V F132L/F93A A315S/N194S C282D/C282N

F344Y/D296A M319I/C208A F132L/L323C A315S/L169V C282D/S329P

F344Y/D296L M319I/C208S F132L/L323V A315S/K225D C282D/I45D

F344Y/T314A M319I/E240A F132L/T83G A315S/K225S C282D/I45L

F344Y/T314E M319I/E240T F132L/T83N A315S/A63I C282D/E258A

F344Y/F267Y M319I/N148H F132L/Q92R A315S/A63P C282D/A272E

F344Y/E71N M319I/F94L F132L/F267I A315S/I180L C282D/T312A

F344Y/E252Q M319I/F94Y F132L/F267Q A315S/I180V C282D/T312R

F344Y/I367V M319I/V150L F132L/E4K A315S/H151D C282D/M327Q

F344Y/A31M M319I/F68P F132L/E90D A315S/T220I C282D/M327T

F344Y/A31S M319I/N148R F132L/T312K A315S/T220S C282D/N174Y

F344Y/F93A M319I/K361R F132L/T312N A315S/L246I C282D/L340I

F344Y/L323C M319I/Q280E F132L/L241V A315S/A272P C282D/L340M

F344Y/L323V M319I/Q280R F132L/V255I A315S/S353E C282D/A189H

F344Y/T83G M319I/K225E F132L/F344G A315S/S353K C282D/A189Y

F344Y/T83N M319I/K225G F132L/I76L A315S/A256D C282D/N194R

F344Y/Q92R M319I/L238A F132L/I76M A315S/A256E C282D/N194S

F344Y/F267I M319I/L238S F132L/G138K A315S/R224L C282D/L169V

F344Y/F267Q M319I/C269A F132L/L238F A315S/A134M C282D/K225D

F344Y/E4K M319I/C269I F132L/L238T A315S/V359E C282D/K225S

F344Y/E90D M319I/D296P F132L/I35L A315S/V359K C282D/A63I Positions Positions Positions Positions Positions

F344Y/T312K M319I/F140Y F132L/I35V A315S/S333A C282D/A63P

F344Y/T312N M319I/I24L F132L/C208A A315S/S333E C282D/I180L

F344Y/L241V M319I/I24V F132L/C208S A315S/T352D C282D/I180V

F344Y/V255I M319I/D170S F132L/E240A A315S/T352E C282D/H151D

F344Y/F344G M319I/V229M F132L/E240T A315S/M157F C282D/T220I

F344Y/I76L M319I/E360A F132L/N148H A315S/M157S C282D/T220S

F344Y/I76M M319I/S322V F132L/F94L A315S/D14G C282D/L246I

F344Y/G138K M319I/F347I F132L/F94Y A315S/D296A C282D/A272P

F344Y/L238F M319I/V221F F132L/V150L A315S/D296L C282D/S353E

F344Y/L238T M319I/V221I F132L/F68P A315S/T314A C282D/S353K

F344Y/I35L M319I/G245S F132L/N148R A315S/T314E C282D/A256D

F344Y/I35V M319I/Q92C F132L/K361R A315S/F267Y C282D/A256E

F344Y/C208A M319I/Q92S F132L/Q280E A315S/E71N C282D/R224L

F344Y/C208S M319I/F230A F132L/Q280R A315S/E252Q C282D/A134M

F344Y/E240A M319I/F230N F132L/K225E A315S/I367V C282D/V359E

F344Y/E240T M319I/S87P F132L/K225G A315S/A31M C282D/V359K

F344Y/N148H M319I/S87Q F132L/L238A A315S/A31S C282D/S333A

F344Y/F94L M319I/L98H F132L/L238S A315S/F93A C282D/S333E

F344Y/F94Y M319I/S70K F132L/C269A A315S/L323C C282D/T352D

F344Y/V150L M319I/F351A F132L/C269I A315S/L323V C282D/T352E

F344Y/F68P M319I/F351V F132L/D296P A315S/T83G C282D/M157F

F344Y/N148R M319I/M157Y F132L/F140Y A315S/T83N C282D/M157S

F344Y/K361R M319I/C44F F132L/I24L A315S/Q92R C282D/D14G

F344Y/Q280E M319I/C44Y F132L/I24V A315S/F267I C282D/D296A

F344Y/Q280R M319I/I3L F132L/D170S A315S/F267Q C282D/D296L

F344Y/K225E M319I/I3M F132L/V229M A315S/E4K C282D/T314A

F344Y/K225G M319V/G245A F132L/E360A A315S/E90D C282D/T314E

F344Y/L238A M319V/G245C F132L/S322V A315S/T312K C282D/F267Y

F344Y/L238S M319V/C282E F132L/F347I A315S/T312N C282D/E71N

F344Y/C269A M319V/C282I F132L/V221F A315S/L241V C282D/E252Q

F344Y/C269I M319V/F335L F132L/V221I A315S/V255I C282D/I367V

F344Y/D296P M319V/T248A F132L/G245S A315S/F344G C282D/A31M

F344Y/F140Y M319V/T248D F132L/Q92C A315S/I76L C282D/A31S

F344Y/I24L M319V/L284S F132L/Q92S A315S/I76M C282D/F93A

F344Y/I24V M319V/N350K F132L/F230A A315S/G138K C282D/L323C

F344Y/D170S M319V/N350R F132L/F230N A315S/L238F C282D/L323V

F344Y/V229M M319V/F132L F132L/S87P A315S/L238T C282D/T83G

F344Y/E360A M319V/I287L F132L/S87Q A315S/I35L C282D/T83N

F344Y/S322V M319V/V36I F132L/L98H A315S/I35V C282D/Q92R

F344Y/F347I M319V/V36L F132L/S70K A315S/C208A C282D/F267I

F344Y/V221F M319V/H131V F132L/F351A A315S/C208S C282D/F267Q

F344Y/V221I M319V/H131Y F132L/F351V A315S/E240A C282D/E4K Positions Positions Positions Positions Positions

F344Y/G245S M319V/S243E F132L/M157Y A315S/E240T C282D/E90D

F344Y/Q92C M319V/I211L F132L/C44F A315S/N148H C282D/T312K

F344Y/Q92S M319V/I211V F132L/C44Y A315S/F94L C282D/T312N

F344Y/F230A M319V/I91F F132L/I3L A315S/F94Y C282D/L241V

F344Y/F230N M319V/E360G F132L/I3M A315S/V150L C282D/V255I

F344Y/S87P M319V/E360L I287L/V36I A315S/F68P C282D/F344G

F344Y/S87Q M319V/A315R I287L/V36L A315S/N148R C282D/I76L

F344Y/L98H M319V/A315S I287L/H131V A315S/K361R C282D/I76M

F344Y/S70K M319V/C282S I287L/H131Y A315S/Q280E C282D/G138K

F344Y/F351A M319V/C282V I287L/S243E A315S/Q280R C282D/L238F

F344Y/F351V M319V/G135A I287L/I211L A315S/K225E C282D/L238T

F344Y/M157Y M319V/V221C I287L/I211V A315S/K225G C282D/I35L

F344Y/C44F M319V/V221M I287L/I91F A315S/L238A C282D/I35V

F344Y/C44Y M319V/R247M I287L/E360G A315S/L238S C282D/C208A

F344Y/I3L M319V/R247N I287L/E360L A315S/C269A C282D/C208S

F344Y/I3M M319V/I91L I287L/A315R A315S/C269I C282D/E240A

V165A/V218F M319V/I91V I287L/A315S A315S/D296P C282D/E240T

V165A/N96S M319V/M160H I287L/C282S A315S/F140Y C282D/N148H

V165A/F347Y M319V/L293F I287L/C282V A315S/I24L C282D/F94L

V165A/M206C M319V/L293S I287L/G135A A315S/I24V C282D/F94Y

V165A/M206L M319V/L66F I287L/V221C A315S/D170S C282D/V150L

V165A/P129V M319V/C282D I287L/V221M A315S/V229M C282D/F68P

V165A/T65A M319V/A222H I287L/R247M A315S/E360A C282D/N148R

V165A/I106V M319V/A222L I287L/R247N A315S/S322V C282D/K361R

V165A/P186Q M319V/E356S I287L/I91L A315S/F347I C282D/Q280E

V165A/M319I M319V/S109G I287L/I91V A315S/V221F C282D/Q280R

V165A/M319V M319V/I290L I287L/M160H A315S/V221I C282D/K225E

V165A/G245A M319V/I290M I287L/L293F A315S/G245S C282D/K225G

V165A/G245C M319V/L330M I287L/L293S A315S/Q92C C282D/L238A

V165A/C282E M319V/H131C I287L/L66F A315S/Q92S C282D/L238S

V165A/C282I M319V/A189G I287L/C282D A315S/F230A C282D/C269A

V165A/F335L M319V/Q193K I287L/A222H A315S/F230N C282D/C269I

V165A/T248A M319V/Q193R I287L/A222L A315S/S87P C282D/D296P

V165A/T248D M319V/L242I I287L/E356S A315S/S87Q C282D/F140Y

V165A/L284S M319V/Q108H I287L/S109G A315S/L98H C282D/I24L

V165A/N350K M319V/F68V I287L/I290L A315S/S70K C282D/I24V

V165A/N350R M319V/G100S I287L/I290M A315S/F351A C282D/D170S

V165A/F132L M319V/G100T I287L/L330M A315S/F351V C282D/V229M

V165A/I287L M319V/L323I I287L/H131C A315S/M157Y C282D/E360A

V165A/V36I M319V/L323M I287L/A189G A315S/C44F C282D/S322V

V165A/V36L M319V/Q277D I287L/Q193K A315S/C44Y C282D/F347I

V165A/H131V M319V/Q277E I287L/Q193R A315S/I3L C282D/V221F Positions Positions Positions Positions Positions

V165A/H131Y M319V/C269N I287L/L242I A315S/I3M C282D/V221I

V165A/S243E M319V/C269T I287L/Q108H C282S/C282V C282D/G245S

V165A/I211L M319V/A326F I287L/F68V C282S/G135A C282D/Q92C

V165A/I211V M319V/A326I I287L/G100S C282S/V221C C282D/Q92S

V165A/I91F M319V/L152F I287L/G100T C282S/V221M C282D/F230A

V165A/E360G M319V/C282N I287L/L323I C282S/R247M C282D/F230N

V165A/E360L M319V/S329P I287L/L323M C282S/R247N C282D/S87P

V165A/A315R M319V/I45D I287L/Q277D C282S/I91L C282D/S87Q

V165A/A315S M319V/I45L I287L/Q277E C282S/I91V C282D/L98H

V165A/C282S M319V/E258A I287L/C269N C282S/M160H C282D/S70K

V165A/C282V M319V/A272E I287L/C269T C282S/L293F C282D/F351A

V165A/G135A M319V/T312A I287L/A326F C282S/L293S C282D/F351V

V165A/V221C M319V/T312R I287L/A326I C282S/L66F C282D/M157Y

V165A/V221M M319V/M327Q I287L/L152F C282S/C282D C282D/C44F

V165A/R247M M319V/M327T I287L/C282N C282S/A222H C282D/C44Y

V165A/R247N M319V/N174Y I287L/S329P C282S/A222L C282D/I3L

V165A/I91L M319V/L340I I287L/I45D C282S/E356S C282D/I3M

V165A/I91V M319V/L340M I287L/I45L C282S/S109G A222H/A222L

V165A/M160H M319V/A189H I287L/E258A C282S/I290L A222H/E356S

V165A/L293F M319V/A189Y I287L/A272E C282S/I290M A222H/S109G

V165A/L293S M319V/N194R I287L/T312A C282S/L330M A222H/I290L

V165A/L66F M319V/N194S I287L/T312R C282S/H131C A222H/I290M

V165A/C282D M319V/L169V I287L/M327Q C282S/A189G A222H/L330M

V165A/A222H M319V/K225D I287L/M327T C282S/Q193K A222H/H131C

V165A/A222L M319V/K225S I287L/N174Y C282S/Q193R A222H/A189G

V165A/E356S M319V/A63I I287L/L340I C282S/L242I A222H/Q193K

V165A/S109G M319V/A63P I287L/L340M C282S/Q108H A222H/Q193R

V165A/I290L M319V/I180L I287L/A189H C282S/F68V A222H/L242I

V165A/I290M M319V/I180V I287L/A189Y C282S/G100S A222H/Q108H

V165A/L330M M319V/H151D I287L/N194R C282S/G100T A222H/F68V

V165A/H131C M319V/T220I I287L/N194S C282S/L323I A222H/G100S

V165A/A189G M319V/T220S I287L/L169V C282S/L323M A222H/G100T

V165A/Q193K M319V/L246I I287L/K225D C282S/Q277D A222H/L323I

V165A/Q193R M319V/A272P I287L/K225S C282S/Q277E A222H/L323M

V165A/L242I M319V/S353E I287L/A63I C282S/C269N A222H/Q277D

V165A/Q108H M319V/S353K I287L/A63P C282S/C269T A222H/Q277E

V165A/F68V M319V/A256D I287L/I180L C282S/A326F A222H/C269N

V165A/G100S M319V/A256E I287L/I180V C282S/A326I A222H/C269T

V165A/G100T M319V/R224L I287L/H151D C282S/L152F A222H/A326F

V165A/L323I M319V/A134M I287L/T220I C282S/C282N A222H/A326I

V165A/L323M M319V/V359E I287L/T220S C282S/S329P A222H/L152F

V165A/Q277D M319V/V359K I287L/L246I C282S/I45D A222H/C282N Positions Positions Positions Positions Positions

V165A/Q277E M319V/S333A I287L/A272P C282S/I45L A222H/S329P

V165A/C269N M319V/S333E I287L/S353E C282S/E258A A222H/I45D

V165A/C269T M319V/T352D I287L/S353K C282S/A272E A222H/I45L

V165A/A326F M319V/T352E I287L/A256D C282S/T312A A222H/E258A

V165A/A326I M319V/M157F I287L/A256E C282S/T312R A222H/A272E

V165A/L152F M319V/M157S I287L/R224L C282S/M327Q A222H/T312A

V165A/C282N M319V/D14G I287L/A134M C282S/M327T A222H/T312R

V165A/S329P M319V/D296A I287L/V359E C282S/N174Y A222H/M327Q

V165A/I45D M319V/D296L I287L/V359K C282S/L340I A222H/M327T

V165A/I45L M319V/T314A I287L/S333A C282S/L340M A222H/N174Y

V165A/E258A M319V/T314E I287L/S333E C282S/A189H A222H/L340I

V165A/A272E M319V/F267Y I287L/T352D C282S/A189Y A222H/L340M

V165A/T312A M319V/E71N I287L/T352E C282S/N194R A222H/A189H

V165A/T312R M319V/E252Q I287L/M157F C282S/N194S A222H/A189Y

V165A/M327Q M319V/ 1367V I287L/M157S C282S/L169V A222H/N194R

V165A/M327T M319V/A31M I287L/D14G C282S/K225D A222H/N194S

V165A/N174Y M319V/A31S I287L/D296A C282S/K225S A222H/L169V

V165A/L340I M319V/F93A I287L/D296L C282S/A63I A222H/K225D

V165A/L340M M319V/L323C I287L/T314A C282S/A63P A222H/K225S

V165A/A189H M319V/L323V I287L/T314E C282S/I180L A222H/A63I

V165A/A189Y M319V/T83G I287L/F267Y C282S/I180V A222H/A63P

V165A/N194R M319V/T83N I287L/E71N C282S/H151D A222H/I180L

V165A/N194S M319V/Q92R I287L/E252Q C282S/T220I A222H/I180V

V165A/L169V M319V/F267I I287L/I367V C282S/T220S A222H/H151D

V165A/K225D M319V/F267Q I287L/A31M C282S/L246I A222H/T220I

V165A/K225S M319V/E4K I287L/A31S C282S/A272P A222H/T220S

V165A/A63I M319V/E90D I287L/F93A C282S/S353E A222H/L246I

V165A/A63P M319V/T312K I287L/L323C C282S/S353K A222H/A272P

V165A/I180L M319V/T312N I287L/L323V C282S/A256D A222H/S353E

V165A/I180V M319V/L241V I287L/T83G C282S/A256E A222H/S353K

V165A/H151D M319V/V255I I287L/T83N C282S/R224L A222H/A256D

V165A/T220I M319V/F344G I287L/Q92R C282S/A134M A222H/A256E

V165A/T220S M319V/I76L I287L/F267I C282S/V359E A222H/R224L

V165A/L246I M319V/I76M I287L/F267Q C282S/V359K A222H/A134M

V165A/A272P M319V/G138K I287L/E4K C282S/S333A A222H/V359E

V165A/S353E M319V/L238F I287L/E90D C282S/S333E A222H/V359K

V165A/S353K M319V/L238T I287L/T312K C282S/T352D A222H/S333A

V165A/A256D M319V/I35L I287L/T312N C282S/T352E A222H/S333E

V165A/A256E M319V/I35V I287L/L241V C282S/M157F A222H/T352D

V165A/R224L M319V/C208A I287L/V255I C282S/M157S A222H/T352E

V165A/A134M M319V/C208S I287L/F344G C282S/D14G A222H/M157F

V165A/V359E M319V/E240A I287L/I76L C282S/D296A A222H/M157S Positions Positions Positions Positions Positions

V165A/V359K M319V/E240T I287L/I76M C282S /D296L A222H/D14G

V165A/ S333A M319V/N148H I287L/G138K C282S/T314A A222H/D296A

V165A/ S333E M319V/F94L I287L/L238F C282S /T314E A222H/D296L

V165A/T352D M319V/F94Y I287L/L238T C282S /F267Y A222H/T314A

V165A/T352E M319V/V150L I287L/I35L C282S /E71N A222H/T314E

V165A/M157F M319V/F68P I287L/I35V C282S /E252Q A222H/F267Y

V165A/M157S M319V/N148R I287L/C208A C282S /I367V A222H/E71N

V165A/D14G M319V/K361R I287L/C208S C282S /A31M A222H/E252Q

A222H/I367V G100T/ S70K M327Q/F267I S353E/I367V L323V/E240A

A222H/A31M G100T/F351A M327Q/F267Q S353E/A31M L323V/E240T

A222H/A31 S G100T/F351V M327Q /E4K S353E/A31 S L323V/N148H

A222H/F93A G100T/M157Y M327Q/E90D S353E/F93A L323V/F94L

A222H/L323C G100T/C44F M327Q /T312K S353E/L323C L323V/F94Y

A222H/L323V G100T/C44Y M327Q /T312N S353E/L323V L323V/V150L

A222H/T83G G100T/I3L M327Q /L241V S353E/T83G L323V/F68P

A222H/T83N G100T/I3M M327Q/V255I S353E/T83N L323V/N148R

A222H/Q92R L323I/L323M M327Q/F344G S353E/Q92R L323V/K361R

A222H/F267I L323I/Q277D M327Q/I76L S353E/F267I L323V/Q280E

A222H/F267Q L323I/Q277E M327Q /I76M S353E/F267Q L323V/Q280R

A222H/E4K L323I/C269N M327Q/G138K S353E/E4K L323V/K225E

A222H/E90D L323I/C269T M327Q /L238F S353E/E90D L323V/K225G

A222H/T312K L323I/A326F M327Q/L238T S353E/T312K L323V/L238A

A222H/T312N L323I/A326I M327Q/I35L S353E/T312N L323V/L238S

A222H/L241V L323I/L152F M327Q /I35V S353E/L241V L323V/C269A

A222H/V255I L323I/C282N M327Q /C208A S353E/V255I L323V/C269I

A222H/F344G L323I/ S329P M327Q/C208S S353E/F344G L323V/D296P

A222H/I76L L323I/I45D M327Q /E240A S353E/I76L L323V/F140Y

A222H/I76M L323I/I45L M327Q/E240T S353E/I76M L323V/I24L

A222H/G138K L323I/E258A M327Q/N148H S353E/G138K L323V/I24V

A222H/L238F L323I/A272E M327Q/F94L S353E/L238F L323V/D170S

A222H/L238T L323I/T312A M327Q /F94Y S353E/L238T L323V/V229M

A222H/I35L L323I/T312R M327Q /V150L S353E/I35L L323V/E360A

A222H/I35V L323I/M327Q M327Q/F68P S353E/I35V L323V/ S322V

A222H/C208A L323I/M327T M327Q /N148R S353E/C208A L323V/F347I

A222H/C208S L323I/N174Y M327Q /K361R S353E/C208S L323V/V221F

A222H/E240A L323I/L340I M327Q /Q280E S353E/E240A L323V/V221I

A222H/E240T L323I/L340M M327Q /Q280R S353E/E240T L323V/G245S

A222H/N148H L323I/A189H M327Q /K225E S353E/N148H L323V/Q92C

A222H/F94L L323I/A189Y M327Q/K225G S353E/F94L L323V/Q92S

A222H/F94Y L323I/N194R M327Q /L238A S353E/F94Y L323V/F230A

A222H/V150L L323I/N194S M327Q /L238S S353E/V150L L323V/F230N

A222H/F68P L323I/L169V M327Q /C269A S353E/F68P L323V/ S87P Positions Positions Positions Positions Positions

A222H/N148R L323I/K225D M327Q /C269I S353E/N148R L323V/ S87Q

A222H/K361R L323I/K225S M327Q/D296P S353E/K361R L323V/L98H

A222H/Q280E L323I/A63I M327Q/F140Y S353E/Q280E L323V/ S70K

A222H/Q280R L323I/A63P M327Q/I24L S353E/Q280R L323V/F351A

A222H/K225E L323I/I180L M327Q /I24V S353E/K225E L323V/F351V

A222H/K225G L323I/I180V M327Q/D170S S353E/K225G L323V/M157Y

A222H/L238A L323I/H151D M327Q /V229M S353E/L238A L323V/C44F

A222H/L238S L323I/T220I M327Q /E360A S353E/L238S L323V/C44Y

A222H/C269A L323I/T220S M327Q/ S322V S353E/C269A L323V/I3L

A222H/C269I L323I/L246I M327Q/F347I S353E/C269I L323V/I3M

A222H/D296P L323I/A272P M327Q/V221F S353E/D296P T83G/T83N

A222H/F140Y L323I/ S353E M327Q/V221I S353E/F140Y T83G/Q92R

A222H/I24L L323I/ S353K M327Q/G245S S353E/I24L T83G/F267I

A222H/I24V L323I/A256D M327Q/Q92C S353E/I24V T83G/F267Q

A222H/D170S L323I/A256E M327Q /Q92S S353E/D170S T83G/E4K

A222H/V229M L323I/R224L M327Q/F230A S353E/V229M T83G/E90D

A222H/E360A L323I/A134M M327Q/F230N S353E/E360A T83G/T312K

A222H/ S322V L323I/V359E M327Q/ S87P S353E/ S322V T83G/T312N

A222H/F347I L323I/V359K M327Q / S87Q S353E/F347I T83G/L241V

A222H/V221F L323I/ S333A M327Q/L98H S353E/V221F T83G/V255I

A222H/V221I L323I/ S333E M327Q / S70K S353E/V221I T83G/F344G

A222H/G245S L323I/T352D M327Q/F351A S353E/G245S T83G/I76L

A222H/Q92C L323I/T352E M327Q/F351V S353E/Q92C T83G/I76M

A222H/Q92S L323I/M157F M327Q /M157Y S353E/Q92S T83G/G138K

A222H/F230A L323I/M157S M327Q /C44F S353E/F230A T83G/L238F

A222H/F230N L323I/D14G M327Q/C44Y S353E/F230N T83G/L238T

A222H/ S87P L323I/D296A M327Q /I3L S353E/ S87P T83G/I35L

A222H/ S87Q L323I/D296L M327Q/I3M S353E/ S87Q T83G/I35V

A222H/L98H L323I/T314A M327T/N174Y S353E/L98H T83G/C208A

A222H/ S70K L323I/T314E M327T/L340I S353E/ S70K T83G/C208S

A222H/F351A L323I/F267Y M327T/L340M S353E/F351A T83G/E240A

A222H/F351V L323I/E71N M327T/A189H S353E/F351V T83G/E240T

A222H/M157Y L323I/E252Q M327T/A189Y S353E/M157Y T83G/N148H

A222H/C44F L323I/I367V M327T/N194R S353E/C44F T83G/F94L

A222H/C44Y L323I/A31M M327T/N194S S353E/C44Y T83G/F94Y

A222H/I3L L323I/A31 S M327T/L169V S353E/I3L T83G/V150L

A222H/I3M L323I/F93A M327T/K225D S353E/I3M T83G/F68P

A222L/E356S L323I/L323C M327T/K225S S353K/A256D T83G/N148R

A222L/ S 109G L323I/L323V M327T/A63I S353K/A256E T83G/K361R

A222L/I290L L323I/T83G M327T/A63P S353K/R224L T83G/Q280E

A222L/I290M L323I/T83N M327T/I180L S353K/A134M T83G/Q280R

A222L/L330M L323I/Q92R M327T/I180V S353K/V359E T83G/K225E Positions Positions Positions Positions Positions

A222L/H131C L323I/F267I M327T/H151D S353K/V359K T83G/K225G

A222L/A189G L323I/F267Q M327T/T220I S353K/ S333A T83G/L238A

A222L/Q193K L323I/E4K M327T/T220S S353K/ S333E T83G/L238S

A222L/Q193R L323I/E90D M327T/L246I S353K/T352D T83G/C269A

A222L/L242I L323I/T312K M327T/A272P S353K/T352E T83G/C269I

A222L/Q108H L323I/T312N M327T/ S353E S353K/M157F T83G/D296P

A222L/F68V L323I/L241V M327T/ S353K S353K/M157S T83G/F140Y

A222L/G100S L323I/V255I M327T/A256D S353K/D14G T83G/I24L

A222L/G100T L323I/F344G M327T/A256E S353K/D296A T83G/I24V

A222L/L323I L323I/I76L M327T/R224L S353K/D296L T83G/D170S

A222L/L323M L323I/I76M M327T/A134M S353K/T314A T83G/V229M

A222L/Q277D L323I/G138K M327T/V359E S353K/T314E T83G/E360A

A222L/Q277E L323I/L238F M327T/V359K S353K/F267Y T83G/ S322V

A222L/C269N L323I/L238T M327T/ S333A S353K/E71N T83G/F347I

A222L/C269T L323I/I35L M327T/ S333E S353K/E252Q T83G/V221F

A222L/A326F L323I/I35V M327T/T352D S353K/I367V T83G/V221I

A222L/A326I L323I/C208A M327T/T352E S353K/A31M T83G/G245S

A222L/L152F L323I/C208S M327T/M157F S353K/A31 S T83G/Q92C

A222L/C282N L323I/E240A M327T/M157S S353K/F93A T83G/Q92S

A222L/ S329P L323I/E240T M327T/D14G S353K/L323C T83G/F230A

A222L/I45D L323I/N148H M327T/D296A S353K/L323V T83G/F230N

A222L/I45L L323I/F94L M327T/D296L S353K/T83G T83G/ S87P

A222L/E258A L323I/F94Y M327T/T314A S353K/T83N T83G/ S87Q

A222L/A272E L323I/V150L M327T/T314E S353K/Q92R T83G/L98H

A222L/T312A L323I/F68P M327T/F267Y S353K/F267I T83G/ S70K

A222L/T312R L323I/N148R M327T/E71N S353K/F267Q T83G/F351A

A222L/M327Q L323I/K361R M327T/E252Q S353K/E4K T83G/F351V

A222L/M327T L323I/Q280E M327T/I367V S353K/E90D T83G/M157Y

A222L/N174Y L323I/Q280R M327T/A31M S353K/T312K T83G/C44F

A222L/L340I L323I/K225E M327T/A31 S S353K/T312N T83G/C44Y

A222L/L340M L323I/K225G M327T/F93A S353K/L241V T83G/I3L

A222L/A189H L323I/L238A M327T/L323C S353K/V255I T83G/I3M

A222L/A189Y L323I/L238S M327T/L323V S353K/F344G T83N/Q92R

A222L/N194R L323I/C269A M327T/T83G S353K/I76L T83N/F267I

A222L/N194S L323I/C269I M327T/T83N S353K/I76M T83N/F267Q

A222L/L169V L323I/D296P M327T/Q92R S353K/G138K T83N/E4K

A222L/K225D L323I/F140Y M327T/F267I S353K/L238F T83N/E90D

A222L/K225S L323I/I24L M327T/F267Q S353K/L238T T83N/T312K

A222L/A63I L323I/I24V M327T/E4K S353K/I35L T83N/T312N

A222L/A63P L323I/D170S M327T/E90D S353K/I35V T83N/L241V

A222L/I180L L323I/V229M M327T/T312K S353K/C208A T83N/V255I

A222L/I180V L323I/E360A M327T/T312N S353K/C208S T83N/F344G Positions Positions Positions Positions Positions

A222L/H151D L323I/ S322V M327T/L241V S353K/E240A T83N/I76L

A222L/T220I L323I/F347I M327T/V255I S353K/E240T T83N/I76M

A222L/T220S L323I/V221F M327T/F344G S353K/N148H T83N/G138K

A222L/L246I L323I/V221I M327T/I76L S353K/F94L T83N/L238F

A222L/A272P L323I/G245S M327T/I76M S353K/F94Y T83N/L238T

A222L/ S353E L323I/Q92C M327T/G138K S353K/V150L T83N/I35L

A222L/ S353K L323I/Q92S M327T/L238F S353K/F68P T83N/I35V

A222L/A256D L323I/F230A M327T/L238T S353K/N148R T83N/C208A

A222L/A256E L323I/F230N M327T/I35L S353K/K361R T83N/C208S

A222L/R224L L323I/ S87P M327T/I35V S353K/Q280E T83N/E240A

A222L/A134M L323I/ S87Q M327T/C208A S353K/Q280R T83N/E240T

A222L/V359E L323I/L98H M327T/C208S S353K/K225E T83N/N148H

A222L/V359K L323I/ S70K M327T/E240A S353K/K225G T83N/F94L

A222L/ S333A L323I/F351A M327T/E240T S353K/L238A T83N/F94Y

A222L/ S333E L323I/F351V M327T/N148H S353K/L238S T83N/V150L

A222L/T352D L323I/M157Y M327T/F94L S353K/C269A T83N/F68P

A222L/T352E L323I/C44F M327T/F94Y S353K/C269I T83N/N148R

A222L/M157F L323I/C44Y M327T/V150L S353K/D296P T83N/K361R

A222L/M157S L323I/I3L M327T/F68P S353K/F140Y T83N/Q280E

A222L/D14G L323I/I3M M327T/N148R S353K/I24L T83N/Q280R

A222L/D296A L323M/Q277D M327T/K361R S353K/I24V T83N/K225E

A222L/D296L L323M/Q277E M327T/Q280E S353K/D170S T83N/K225G

A222L/T314A L323M/C269N M327T/Q280R S353K/V229M T83N/L238A

A222L/T314E L323M/C269T M327T/K225E S353K/E360A T83N/L238S

A222L/F267Y L323M/A326F M327T/K225G S353K/ S322V T83N/C269A

A222L/E71N L323M/A326I M327T/L238A S353K/F347I T83N/C269I

A222L/E252Q L323M/L152F M327T/L238S S353K/V221F T83N/D296P

A222L/I367V L323M/C282N M327T/C269A S353K/V221I T83N/F140Y

A222L/A31M L323M/ S329P M327T/C269I S353K/G245S T83N/I24L

A222L/A31S L323M/I45D M327T/D296P S353K/Q92C T83N/I24V

A222L/F93A L323M/I45L M327T/F140Y S353K/Q92S T83N/D170S

A222L/L323C L323M/E258A M327T/I24L S353K/F230A T83N/V229M

A222L/L323V L323M/A272E M327T/I24V S353K/F230N T83N/E360A

A222L/T83G L323M/T312A M327T/D170S S353K/ S87P T83N/ S322V

A222L/T83N L323M/T312R M327T/V229M S353K/ S87Q T83N/F347I

A222L/Q92R L323M/M327Q M327T/E360A S353K/L98H T83N/V221F

A222L/F267I L323M/M327T M327T/ S322V S353K/ S70K T83N/V221I

A222L/F267Q L323M/N174Y M327T/F347I S353K/F351A T83N/G245S

A222L/E4K L323M/L340I M327T/V221F S353K/F351V T83N/Q92C

A222L/E90D L323M/L340M M327T/V221I S353K/M157Y T83N/Q92S

A222L/T312K L323M/A189H M327T/G245S S353K/C44F T83N/F230A

A222L/T312N L323M/A189Y M327T/Q92C S353K/C44Y T83N/F230N Positions Positions Positions Positions Positions

A222L/L241V L323M/N194R M327T/Q92S S353K/I3L T83N/ S87P

A222L/V255I L323M/N194S M327T/F230A S353K/I3M T83N/ S87Q

A222L/F344G L323M/L169V M327T/F230N A256D/A256E T83N/L98H

A222L/I76L L323M/K225D M327T/ S87P A256D/R224L T83N/ S70K

A222L/I76M L323M/K225S M327T/ S87Q A256D /A134M T83N/F351A

A222L/G138K L323M/A63I M327T/L98H A256D/V359E T83N/F351V

A222L/L238F L323M/A63P M327T/ S70K A256D /V359K T83N/M157Y

A222L/L238T L323M/I180L M327T/F351A A256D/ S333A T83N/C44F

A222L/I35L L323M/I180V M327T/F351V A256D / S333E T83N/C44Y

A222L/I35V L323M/H151D M327T/M157Y A256D/T352D T83N/I3L

A222L/C208A L323M/T220I M327T/C44F A256D /T352E T83N/I3M

A222L/C208S L323M/T220S M327T/C44Y A256D /M157F Q92R/F267I

A222L/E240A L323M/L246I M327T/I3L A256D /M157S Q92R/F267Q

A222L/E240T L323M/A272P M327T/I3M A256D/D14G Q92R/E4K

A222L/N148H L323M/ S353E N174Y/L340I A256D /D296A Q92R/E90D

A222L/F94L L323M/ S353K N174Y/L340M A256D/D296L Q92R/T312K

A222L/F94Y L323M/A256D N174Y/A189H A256D/T314A Q92R/T312N

A222L/V150L L323M/A256E N174Y/A189Y A256D /T314E Q92R/L241V

A222L/F68P L323M/R224L N174Y/N194R A256D/F267Y Q92R/V255I

A222L/N148R L323M/A134M N174Y/N194S A256D /E71N Q92R/F344G

A222L/K361R L323M/V359E N174Y/L169V A256D/E252Q Q92R/I76L

A222L/Q280E L323M/V359K N174Y/K225D A256D /I367V Q92R/I76M

A222L/Q280R L323M/ S333A N174Y/K225S A256D/A31M Q92R/G138K

A222L/K225E L323M/ S333E N174Y/A63I A256D/A31 S Q92R/L238F

A222L/K225G L323M/T352D N174Y/A63P A256D /F93A Q92R/L238T

A222L/L238A L323M/T352E N174Y/I180L A256D/L323C Q92R/I35L

A222L/L238S L323M/M157F N174Y/I180V A256D/L323V Q92R/I35V

A222L/C269A L323M/M157S N174Y/H151D A256D /T83G Q92R/C208A

A222L/C269I L323M/D14G N174Y/T220I A256D /T83N Q92R/C208S

A222L/D296P L323M/D296A N174Y/T220S A256D/Q92R Q92R/E240A

A222L/F140Y L323M/D296L N174Y/L246I A256D/F267I Q92R/E240T

A222L/I24L L323M/T314A N174Y/A272P A256D/F267Q Q92R/N148H

A222L/I24V L323M/T314E N174Y/ S353E A256D/E4K Q92R/F94L

A222L/D170S L323M/F267Y N174Y/ S353K A256D /E90D Q92R/F94Y

A222L/V229M L323M/E71N N174Y/A256D A256D/T312K Q92R/V150L

A222L/E360A L323M/E252Q N174Y/A256E A256D/T312N Q92R/F68P

A222L/ S322V L323M/I367V N174Y/R224L A256D/L241V Q92R/N148R

A222L/F347I L323M/A31M N174Y/A134M A256D /V255I Q92R/K361R

A222L/V221F L323M/A31 S N174Y/V359E A256D/F344G Q92R/Q280E

A222L/V221I L323M/F93A N174Y/V359K A256D /I76L Q92R/Q280R

A222L/G245S L323M/L323C N174Y/ S333A A256D/I76M Q92R/K225E

A222L/Q92C L323M/L323V N174Y/ S333E A256D /G138K Q92R/K225G Positions Positions Positions Positions Positions

A222L/Q92S L323M/T83G N174Y/T352D A256D/L238F Q92R/L238A

A222L/F230A L323M/T83N N174Y/T352E A256D/L238T Q92R/L238S

A222L/F230N L323M/Q92R N174Y/M157F A256D/I35L Q92R/C269A

A222L/S87P L323M/F267I N174Y/M157S A256D/I35V Q92R/C269I

A222L/S87Q L323M/F267Q N174Y/D14G A256D/C208A Q92R/D296P

A222L/L98H L323M/E4K N174Y/D296A A256D/C208S Q92R/F140Y

A222L/S70K L323M/E90D N174Y/D296L A256D/E240A Q92R/I24L

A222L/F351A L323M/T312K N174Y/T314A A256D/E240T Q92R/I24V

A222L/F351V L323M/T312N N174Y/T314E A256D/N148H Q92R/D170S

A222L/M157Y L323M/L241V N174Y/F267Y A256D/F94L Q92R/V229M

A222L/C44F L323M/V255I N174Y/E71N A256D/F94Y Q92R/E360A

A222L/C44Y L323M/F344G N174Y/E252Q A256D/V150L Q92R/S322V

A222L/I3L L323M/I76L N174Y/I367V A256D/F68P Q92R/F347I

A222L/I3M L323M/I76M N174Y/A31M A256D/N148R Q92R/V221F

E356S/S109G L323M/G138K N174Y/A31S A256D/K361R Q92R/V221I

E356S/I290L L323M/L238F N174Y/F93A A256D/Q280E Q92R/G245S

E356S/I290M L323M/L238T N174Y/L323C A256D/Q280R Q92R/Q92C

E356S/L330M L323M/I35L N174Y/L323V A256D/K225E Q92R/Q92S

E356S/H131C L323M/I35V N174Y/T83G A256D/K225G Q92R/F230A

E356S/A189G L323M/C208A N174Y/T83N A256D/L238A Q92R/F230N

E356S/Q193K L323M/C208S N174Y/Q92R A256D/L238S Q92R/S87P

E356S/Q193R L323M/E240A N174Y/F267I A256D/C269A Q92R/S87Q

E356S/L242I L323M/E240T N174Y/F267Q A256D/C269I Q92R/L98H

E356S/Q108H L323M/N148H N174Y/E4K A256D/D296P Q92R/S70K

E356S/F68V L323M/F94L N174Y/E90D A256D/F140Y Q92R/F351A

E356S/G100S L323M/F94Y N174Y/T312K A256D/I24L Q92R/F351V

E356S/G100T L323M/V150L N174Y/T312N A256D/I24V Q92R/M157Y

E356S/L323I L323M/F68P N174Y/L241V A256D/D170S Q92R/C44F

E356S/L323M L323M/N148R N174Y/V255I A256D/V229M Q92R/C44Y

E356S/Q277D L323M/K361R N174Y/F344G A256D/E360A Q92R/I3L

E356S/Q277E L323M/Q280E N174Y/I76L A256D/S322V Q92R/I3M

E356S/C269N L323M/Q280R N174Y/I76M A256D/F347I F267I/F267Q

E356S/C269T L323M/K225E N174Y/G138K A256D/V221F F267I/E4K

E356S/A326F L323M/K225G N174Y/L238F A256D/V221I F267I/E90D

E356S/A326I L323M/L238A N174Y/L238T A256D/G245S F267I/T312K

E356S/L152F L323M/L238S N174Y/I35L A256D/Q92C F267I/T312N

E356S/C282N L323M/C269A N174Y/I35V A256D/Q92S F267I/L241V

E356S/S329P L323M/C269I N174Y/C208A A256D/F230A F267I/V255I

E356S/I45D L323M/D296P N174Y/C208S A256D/F230N F267I/F344G

E356S/I45L L323M/F140Y N174Y/E240A A256D/S87P F267I/I76L

E356S/E258A L323M/I24L N174Y/E240T A256D/S87Q F267I/I76M

E356S/A272E L323M/I24V N174Y/N148H A256D/L98H F267I/G138K Positions Positions Positions Positions Positions

E356S/T312A L323M/D170S N174Y/F94L A256D/S70K F267I/L238F

E356S/T312R L323M/V229M N174Y/F94Y A256D/F351A F267I/L238T

E356S/M327Q L323M/E360A N174Y/V150L A256D/F351V F267I/I35L

E356S/M327T L323M/S322V N174Y/F68P A256D/M157Y F267I/I35V

E356S/N174Y L323M/F347I N174Y/N148R A256D/C44F F267I/C208A

E356S/L340I L323M/V221F N174Y/K361R A256D/C44Y F267I/C208S

E356S/L340M L323M/V221I N174Y/Q280E A256D/I3L F267I/E240A

E356S/A189H L323M/G245S N174Y/Q280R A256D/I3M F267I/E240T

E356S/A189Y L323M/Q92C N174Y/K225E A256E/R224L F267I/N148H

E356S/N194R L323M/Q92S N174Y/K225G A256E/A134M F267I/F94L

E356S/N194S L323M/F230A N174Y/L238A A256E/V359E F267I/F94Y

E356S/L169V L323M/F230N N174Y/L238S A256E/V359K F267I/V150L

E356S/K225D L323M/S87P N174Y/C269A A256E/S333A F267I/F68P

E356S/K225S L323M/S87Q N174Y/C269I A256E/S333E F267I/N148R

E356S/A63I L323M/L98H N174Y/D296P A256E/T352D F267I/K361R

E356S/A63P L323M/S70K N174Y/F140Y A256E/T352E F267I/Q280E

E356S/I180L L323M/F351A N174Y/I24L A256E/M157F F267I/Q280R

E356S/I180V L323M/F351V N174Y/I24V A256E/M157S F267I/K225E

E356S/H151D L323M/M157Y N174Y/D170S A256E/D14G F267I/K225G

E356S/T220I L323M/C44F N174Y/V229M A256E/D296A F267I/L238A

E356S/T220S L323M/C44Y N174Y/E360A A256E/D296L F267I/L238S

E356S/L246I L323M/I3L N174Y/S322V A256E/T314A F267I/C269A

E356S/A272P L323M/I3M N174Y/F347I A256E/T314E F267I/C269I

E356S/S353E Q277D/Q277E N174Y/V221F A256E/F267Y F267I/D296P

E356S/S353K Q277D/C269N N174Y/V221I A256E/E71N F267I/F140Y

E356S/A256D Q277D/C269T N174Y/G245S A256E/E252Q F267I/I24L

E356S/A256E Q277D/A326F N174Y/Q92C A256E/I367V F267I/I24V

E356S/R224L Q277D/A326I N174Y/Q92S A256E/A31M F267I/D170S

E356S/A134M Q277D/L152F N174Y/F230A A256E/A31S F267I/V229M

E356S/V359E Q277D/C282N N174Y/F230N A256E/F93A F267I/E360A

E356S/V359K Q277D/S329P N174Y/S87P A256E/L323C F267I/S322V

E356S/S333A Q277D/I45D N174Y/S87Q A256E/L323V F267I/F347I

E356S/S333E Q277D/I45L N174Y/L98H A256E/T83G F267I/V221F

E356S/T352D Q277D/E258A N174Y/S70K A256E/T83N F267I/V221I

E356S/T352E Q277D/A272E N174Y/F351A A256E/Q92R F267I/G245S

E356S/M157F Q277D/T312A N174Y/F351V A256E/F267I F267I/Q92C

E356S/M157S Q277D/T312R N174Y/M157Y A256E/F267Q F267I/Q92S

E356S/D14G Q277D/M327Q N174Y/C44F A256E/E4K F267I/F230A

E356S/D296A Q277D/M327T N174Y/C44Y A256E/E90D F267I/F230N

E356S/D296L Q277D/N174Y N174Y/I3L A256E/T312K F267I/S87P

E356S/T314A Q277D/L340I N174Y/I3M A256E/T312N F267I/S87Q

E356S/T314E Q277D/L340M L340I/L340M A256E/L241V F267I/L98H Positions Positions Positions Positions Positions

E356S/F267Y Q277D/A189H L340I/A189H A256E/V255I F267I/S70K

E356S/E71N Q277D/A189Y L340I/A189Y A256E/F344G F267I/F351A

E356S/E252Q Q277D/N194R L340I/N194R A256E/I76L F267I/F351V

E356S/I367V Q277D/N194S L340I/N194S A256E/I76M F267I/M157Y

E356S/A31M Q277D/L169V L340I/L169V A256E/G138K F267I/C44F

E356S/A31S Q277D/K225D L340I/K225D A256E/L238F F267I/C44Y

E356S/F93A Q277D/K225S L340I/K225S A256E/L238T F267I/I3L

E356S/L323C Q277D/A63I L340I/A63I A256E/I35L F267I/I3M

E356S/L323V Q277D/A63P L340I/A63P A256E/I35V F267Q/E4K

E356S/T83G Q277D/I180L L340I/I180L A256E/C208A F267Q/E90D

E356S/T83N Q277D/I180V L340I/I180V A256E/C208S F267Q/T312K

E356S/Q92R Q277D/H151D L340I/H151D A256E/E240A F267Q/T312N

E356S/F267I Q277D/T220I L340I/T220I A256E/E240T F267Q/L241V

E356S/F267Q Q277D/T220S L340I/T220S A256E/N148H F267Q/V255I

E356S/E4K Q277D/L246I L340I/L246I A256E/F94L F267Q/F344G

E356S/E90D Q277D/A272P L340I/A272P A256E/F94Y F267Q/I76L

E356S/T312K Q277D/S353E L340I/S353E A256E/V150L F267Q/I76M

E356S/T312N Q277D/S353K L340I/S353K A256E/F68P F267Q/G138K

E356S/L241V Q277D/A256D L340I/A256D A256E/N148R F267Q/L238F

E356S/V255I Q277D/A256E L340I/A256E A256E/K361R F267Q/L238T

E356S/F344G Q277D/R224L L340I/R224L A256E/Q280E F267Q/I35L

E356S/I76L Q277D/A134M L340I/A134M A256E/Q280R F267Q/I35V

E356S/I76M Q277D/V359E L340I/V359E A256E/K225E F267Q/C208A

E356S/G138K Q277D/V359K L340I/V359K A256E/K225G F267Q/C208S

E356S/L238F Q277D/S333A L340I/S333A A256E/L238A F267Q/E240A

E356S/L238T Q277D/S333E L340I/S333E A256E/L238S F267Q/E240T

E356S/I35L Q277D/T352D L340I/T352D A256E/C269A F267Q/N148H

E356S/I35V Q277D/T352E L340I/T352E A256E/C269I F267Q/F94L

E356S/C208A Q277D/M157F L340I/M157F A256E/D296P F267Q/F94Y

E356S/C208S Q277D/M157S L340I/M157S A256E/F140Y F267Q/V150L

E356S/E240A Q277D/D14G L340I/D14G A256E/I24L F267Q/F68P

E356S/E240T Q277D/D296A L340I/D296A A256E/I24V F267Q/N148R

E356S/N148H Q277D/D296L L340I/D296L A256E/D170S F267Q/K361R

E356S/F94L Q277D/T314A L340I/T314A A256E/V229M F267Q/Q280E

E356S/F94Y Q277D/T314E L340I/T314E A256E/E360A F267Q/Q280R

E356S/V150L Q277D/F267Y L340I/F267Y A256E/S322V F267Q/K225E

E356S/F68P Q277D/E71N L340I/E71N A256E/F347I F267Q/K225G

E356S/N148R Q277D/E252Q L340I/E252Q A256E/V221F F267Q/L238A

E356S/K361R Q277D/I367V L340I/I367V A256E/V221I F267Q/L238S

E356S/Q280E Q277D/A31M L340I/A31M A256E/G245S F267Q/C269A

E356S/Q280R Q277D/A31S L340I/A31S A256E/Q92C F267Q/C269I

E356S/K225E Q277D/F93A L340I/F93A A256E/Q92S F267Q/D296P Positions Positions Positions Positions Positions

E356S/K225G Q277D/L323C L340I/L323C A256E/F230A F267Q/F140Y

E356S/L238A Q277D/L323V L340I/L323V A256E/F230N F267Q/I24L

E356S/L238S Q277D/T83G L340I/T83G A256E/S87P F267Q/I24V

E356S/C269A Q277D/T83N L340I/T83N A256E/S87Q F267Q/D170S

E356S/C269I Q277D/Q92R L340I/Q92R A256E/L98H F267Q/V229M

E356S/D296P Q277D/F267I L340I/F267I A256E/S70K F267Q/E360A

E356S/F140Y Q277D/F267Q L340I/F267Q A256E/F351A F267Q/S322V

E356S/I24L Q277D/E4K L340I/E4K A256E/F351V F267Q/F347I

E356S/I24V Q277D/E90D L340I/E90D A256E/M157Y F267Q/V221F

E356S/D170S Q277D/T312K L340I/T312K A256E/C44F F267Q/V221I

E356S/V229M Q277D/T312N L340I/T312N A256E/C44Y F267Q/G245S

E356S/E360A Q277D/L241V L340I/L241V A256E/I3L F267Q/Q92C

E356S/S322V Q277D/V255I L340I/V255I A256E/I3M F267Q/Q92S

E356S/F347I Q277D/F344G L340I/F344G R224L/A134M F267Q/F230A

E356S/V221F Q277D/I76L L340I/I76L R224L/V359E F267Q/F230N

E356S/V221I Q277D/I76M L340I/I76M R224L/V359K F267Q/S87P

E356S/G245S Q277D/G138K L340I/G138K R224L/S333A F267Q/S87Q

E356S/Q92C Q277D/L238F L340I/L238F R224L/S333E F267Q/L98H

E356S/Q92S Q277D/L238T L340I/L238T R224L/T352D F267Q/S70K

E356S/F230A Q277D/I35L L340I/I35L R224L/T352E F267Q/F351A

E356S/F230N Q277D/I35V L340I/I35V R224L/M157F F267Q/F351V

E356S/S87P Q277D/C208A L340I/C208A R224L/M157S F267Q/M157Y

E356S/S87Q Q277D/C208S L340I/C208S R224L/D14G F267Q/C44F

E356S/L98H Q277D/E240A L340I/E240A R224L/D296A F267Q/C44Y

E356S/S70K Q277D/E240T L340I/E240T R224L/D296L F267Q/I3L

E356S/F351A Q277D/N148H L340I/N148H R224L/T314A F267Q/I3M

E356S/F351V Q277D/F94L L340I/F94L R224L/T314E E4K/E90D

E356S/M157Y Q277D/F94Y L340I/F94Y R224L/F267Y E4K/T312K

E356S/C44F Q277D/V150L L340I/V150L R224L/E71N E4K/T312N

E356S/C44Y Q277D/F68P L340I/F68P R224L/E252Q E4K/L241V

E356S/I3L Q277D/N148R L340I/N148R R224L/I367V E4K/V255I

E356S/I3M Q277D/K361R L340I/K361R R224L/A31M E4K/F344G

S109G/I290L Q277D/Q280E L340I/Q280E R224L/A31S E4K/I76L

S109G/I290M Q277D/Q280R L340I/Q280R R224L/F93A E4K/I76M

S109G/L330M Q277D/K225E L340I/K225E R224L/L323C E4K/G138K

S109G/H131C Q277D/K225G L340I/K225G R224L/L323V E4K/L238F

S109G/A189G Q277D/L238A L340I/L238A R224L/T83G E4K/L238T

S109G/Q193K Q277D/L238S L340I/L238S R224L/T83N E4K/I35L

S109G/Q193R Q277D/C269A L340I/C269A R224L/Q92R E4K/I35V

S109G/L242I Q277D/C269I L340I/C269I R224L/F267I E4K/C208A

S109G/Q108H Q277D/D296P L340I/D296P R224L/F267Q E4K/C208S

S109G/F68V Q277D/F140Y L340I/F140Y R224L/E4K E4K/E240A Positions Positions Positions Positions Positions

S 109G/G100S Q277D/I24L L340I/I24L R224L/E90D E4K/E240T

S109G/G100T Q277D/I24V L340I/I24V R224L/T312K E4K/N148H

S109G/L323I Q277D/D170S L340I/D170S R224L/T312N E4K/F94L

S 109G/L323M Q277D /V229M L340I/V229M R224L/L241V E4K/F94Y

S 109G/Q277D Q277D /E360A L340I/E360A R224L/V255I E4K/V150L

S109G/Q277E Q277D/ S322V L340I/ S322V R224L/F344G E4K/F68P

S109G/C269N Q277D/F347I L340I/F347I R224L/I76L E4K/N148R

S 109G/C269T Q277D/V221F L340I/V221F R224L/I76M E4K/K361R

S 109G/A326F Q277D/V221I L340I/V221I R224L/G138K E4K/Q280E

S 109G/A326I Q277D/G245S L340I/G245S R224L/L238F E4K/Q280R

S109G/L152F Q277D/Q92C L340I/Q92C R224L/L238T E4K/K225E

S109G/C282N Q277D /Q92S L340I/Q92S R224L/I35L E4K/K225G

S109G/ S329P Q277D/F230A L340I/F230A R224L/I35V E4K/L238A

S109G/I45D Q277D/F230N L340I/F230N R224L/C208A E4K/L238S

S 109G/I45L Q277D/ S87P L340I/ S87P R224L/C208S E4K/C269A

S109G/E258A Q277D / S87Q L340I/ S87Q R224L/E240A E4K/C269I

S109G/A272E Q277D/L98H L340I/L98H R224L/E240T E4K/D296P

S109G/T312A Q277D / S70K L340I/ S70K R224L/N148H E4K/F140Y

S 109G/T312R Q277D/F351A L340I/F351A R224L/F94L E4K/I24L

S 109G/M327Q Q277D/F351V L340I/F351V R224L/F94Y E4K/I24V

S109G/M327T Q277D /M157Y L340I/M157Y R224L/V150L E4K/D170S

S 109G/N174Y Q277D /C44F L340I/C44F R224L/F68P E4K/V229M

S109G/L340I Q277D/C44Y L340I/C44Y R224L/N148R E4K/E360A

S 109G/L340M Q277D /I3L L340I/I3L R224L/K361R E4K/ S322V

S 109G/A189H Q277D/I3M L340I/I3M R224L/Q280E E4K/F347I

S 109G/A189Y Q277E/C269N L340M/A189H R224L/Q280R E4K/V221F

S109G/N194R Q277E/C269T L340M/A189Y R224L/K225E E4K/V221I

S 109G/N194S Q277E/A326F L340M/N194R R224L/K225G E4K/G245S

S109G/L169V Q277E/A326I L340M/N194S R224L/L238A E4K/Q92C

S 109G/K225D Q277E/L152F L340M/L169V R224L/L238S E4K/Q92S

S 109G/K225S Q277E/C282N L340M/K225D R224L/C269A E4K/F230A

S109G/A63I Q277E/ S329P L340M/K225S R224L/C269I E4K/F230N

S109G/A63P Q277E/I45D L340M/A63I R224L/D296P E4K/ S87P

S109G/I180L Q277E/I45L L340M/A63P R224L/F140Y E4K/ S87Q

S 109G/I180V Q277E/E258A L340M/I180L R224L/I24L E4K/L98H

S 109G/H151D Q277E/A272E L340M/I180V R224L/I24V E4K/ S70K

S109G/T220I Q277E/T312A L340M/H151D R224L/D170S E4K/F351A

S109G/T220S Q277E/T312R L340M/T220I R224L/V229M E4K/F351V

S109G/L246I Q277E/M327Q L340M/T220S R224L/E360A E4K/M157Y

S 109G/A272P Q277E/M327T L340M/L246I R224L/ S322V E4K/C44F

S109G/ S353E Q277E/N174Y L340M/A272P R224L/F347I E4K/C44Y

S 109G/ S353K Q277E/L340I L340M/ S353E R224L/V221F E4K/I3L Positions Positions Positions Positions Positions

S109G/A256D Q277E/L340M L340M/S353K R224L/V221I E4K/I3M

S109G/A256E Q277E/A189H L340M/A256D R224L/G245S E90D/T312K

S109G/R224L Q277E/A189Y L340M/A256E R224L/Q92C E90D/T312N

S109G/A134M Q277E/N194R L340M/R224L R224L/Q92S E90D/L241V

S109G/V359E Q277E/N194S L340M/A134M R224L/F230A E90D/V255I

S109G/V359K Q277E/L169V L340M/V359E R224L/F230N E90D/F344G

S109G/S333A Q277E/K225D L340M/V359K R224L/S87P E90D/I76L

S109G/S333E Q277E/K225S L340M/S333A R224L/S87Q E90D/I76M

S109G/T352D Q277E/A63I L340M/S333E R224L/L98H E90D/G138K

S109G/T352E Q277E/A63P L340M/T352D R224L/S70K E90D/L238F

S109G/M157F Q277E/I180L L340M/T352E R224L/F351A E90D/L238T

S109G/M157S Q277E/I180V L340M/M157F R224L/F351V E90D/I35L

S109G/D14G Q277E/H151D L340M/M157S R224L/M157Y E90D/I35V

S109G/D296A Q277E/T220I L340M/D14G R224L/C44F E90D/C208A

S109G/D296L Q277E/T220S L340M/D296A R224L/C44Y E90D/C208S

S109G/T314A Q277E/L246I L340M/D296L R224L/I3L E90D/E240A

S109G/T314E Q277E/A272P L340M/T314A R224L/I3M E90D/E240T

S109G/F267Y Q277E/S353E L340M/T314E A134M/V359E E90D/N148H

S109G/E71N Q277E/S353K L340M/F267Y A134M/V359K E90D/F94L

S109G/E252Q Q277E/A256D L340M/E71N A134M/S333A E90D/F94Y

S109G/I367V Q277E/A256E L340M/E252Q A134M/S333E E90D/V150L

S109G/A31M Q277E/R224L L340M/I367V A134M/T352D E90D/F68P

S109G/A31S Q277E/A134M L340M/A31M A134M/T352E E90D/N148R

S109G/F93A Q277E/V359E L340M/A31S A134M/M157F E90D/K361R

S109G/L323C Q277E/V359K L340M/F93A A134M/M157S E90D/Q280E

S109G/L323V Q277E/S333A L340M/L323C A134M/D14G E90D/Q280R

S109G/T83G Q277E/S333E L340M/L323V A134M/D296A E90D/K225E

S109G/T83N Q277E/T352D L340M/T83G A134M/D296L E90D/K225G

S109G/Q92R Q277E/T352E L340M/T83N A134M/T314A E90D/L238A

S109G/F267I Q277E/M157F L340M/Q92R A134M/T314E E90D/L238S

S109G/F267Q Q277E/M157S L340M/F267I A134M/F267Y E90D/C269A

S109G/E4K Q277E/D14G L340M/F267Q A134M/E71N E90D/C269I

S109G/E90D Q277E/D296A L340M/E4K A134M/E252Q E90D/D296P

S109G/T312K Q277E/D296L L340M/E90D A134M/I367V E90D/F140Y

S109G/T312N Q277E/T314A L340M/T312K A134M/A31M E90D/I24L

S109G/L241V Q277E/T314E L340M/T312N A134M/A31S E90D/I24V

S109G/V255I Q277E/F267Y L340M/L241V A134M/F93A E90D/D170S

S109G/F344G Q277E/E71N L340M/V255I A134M/L323C E90D/V229M

S109G/I76L Q277E/E252Q L340M/F344G A134M/L323V E90D/E360A

S109G/I76M Q277E/I367V L340M/I76L A134M/T83G E90D/S322V

S109G/G138K Q277E/A31M L340M/I76M A134M/T83N E90D/F347I

S109G/L238F Q277E/A31S L340M/G138K A134M/Q92R E90D/V221F Positions Positions Positions Positions Positions

S 109G/L238T Q277E/F93A L340M/L238F A134M/F267I E90D /V221I

S 109G/I35L Q277E/L323C L340M/L238T A134M/F267Q E90D /G245S

S109G/I35V Q277E/L323V L340M/I35L A134M/E4K E90D /Q92C

S109G/C208A Q277E/T83G L340M/I35V A134M/E90D E90D/Q92S

S 109G/C208S Q277E/T83N L340M/C208A A134M/T312K E90D /F230A

S109G/E240A Q277E/Q92R L340M/C208S A134M/T312N E90D /F230N

S 109G/E240T Q277E/F267I L340M/E240A A134M/L241V E90D/ S87P

S 109G/N148H Q277E/F267Q L340M/E240T A134M/V255I E90D/ S87Q

S 109G/F94L Q277E/E4K L340M/N148H A134M/F344G E90D/L98H

S109G/F94Y Q277E/E90D L340M/F94L A134M/I76L E90D/ S70K

S109G/V150L Q277E/T312K L340M/F94Y A134M/I76M E90D /F351A

S 109G/F68P Q277E/T312N L340M/V150L A134M/G138K E90D /F351V

S109G/N148R Q277E/L241V L340M/F68P A134M/L238F E90D/M157Y

S109G/K361R Q277E/V255I L340M/N148R A134M/L238T E90D /C44F

S109G/Q280E Q277E/F344G L340M/K361R A134M/I35L E90D /C44Y

S109G/Q280R Q277E/I76L L340M/Q280E A134M/I35V E90D/I3L

S109G/K225E Q277E/I76M L340M/Q280R A134M/C208A E90D/I3M

S 109G/K225G Q277E/G138K L340M/K225E A134M/C208S T312K/T312N

S109G/L238A Q277E/L238F L340M/K225G A134M/E240A T312K/L241V

S109G/L238S Q277E/L238T L340M/L238A A134M/E240T T312K/V255I

S109G/C269A Q277E/I35L L340M/L238S A134M/N148H T312K/F344G

S 109G/C269I Q277E/I35V L340M/C269A A134M/F94L T312K/I76L

S 109G/D296P Q277E/C208A L340M/C269I A134M/F94Y T312K/I76M

S 109G/F140Y Q277E/C208S L340M/D296P A134M/V150L T312K/G138K

S 109G/I24L Q277E/E240A L340M/F140Y A134M/F68P T312K/L238F

S109G/I24V Q277E/E240T L340M/I24L A134M/N148R T312K/L238T

S 109G/D170S Q277E/N148H L340M/I24V A134M/K361R T312K/I35L

S 109G/V229M Q277E/F94L L340M/D170S A134M/Q280E T312K/I35V

S109G/E360A Q277E/F94Y L340M/V229M A134M/Q280R T312K/C208A

S 109G/ S322V Q277E/V150L L340M/E360A A134M/K225E T312K/C208S

S 109G/F347I Q277E/F68P L340M/ S322V A134M/K225G T312K/E240A

S 109G/V221F Q277E/N148R L340M/F347I A134M/L238A T312K/E240T

S 109G/V221I Q277E/K361R L340M/V221F A134M/L238S T312K/N148H

S 109G/G245S Q277E/Q280E L340M/V221I A134M/C269A T312K/F94L

S 109G/Q92C Q277E/Q280R L340M/G245S A134M/C269I T312K/F94Y

S109G/Q92S Q277E/K225E L340M/Q92C A134M/D296P T312K/V150L

S 109G/F230A Q277E/K225G L340M/Q92S A134M/F140Y T312K/F68P

S 109G/F230N Q277E/L238A L340M/F230A A134M/I24L T312K/N148R

S 109G/ S87P Q277E/L238S L340M/F230N A134M/I24V T312K/K361R

S109G/ S87Q Q277E/C269A L340M/ S87P A134M/D170S T312K/Q280E

S 109G/L98H Q277E/C269I L340M/ S87Q A134M/V229M T312K/Q280R

S109G/ S70K Q277E/D296P L340M/L98H A134M/E360A T312K/K225E Positions Positions Positions Positions Positions

S 109G/F351A Q277E/F140Y L340M/ S70K A134M/ S322V T312K/K225G

S 109G/F351V Q277E/I24L L340M/F351A A134M/F347I T312K/L238A

S 109G/M157Y Q277E/I24V L340M/F351V A134M/V221F T312K/L238S

S109G/C44F Q277E/D170S L340M/M157Y A134M/V221I T312K/C269A

S 109G/C44Y Q277E/V229M L340M/C44F A134M/G245S T312K/C269I

S109G/I3L Q277E/E360A L340M/C44Y A134M/Q92C T312K/D296P

S 109G/I3M Q277E/ S322V L340M/I3L A134M/Q92S T312K/F140Y

I290L/I290M Q277E/F347I L340M/I3M A134M/F230A T312K/I24L

I290L/L330M Q277E/V221F A189H/A189Y A134M/F230N T312K/I24V

I290L/H131C Q277E/V221I A189H/N194R A134M/ S87P T312K/D170S

I290L/A189G Q277E/G245S A189H/N194S A134M/ S87Q T312K/V229M

I290L/Q193K Q277E/Q92C A189H/L169V A134M/L98H T312K/E360A

I290L/Q193R Q277E/Q92S A189H/K225D A134M/ S70K T312K/ S322V

I290L/L242I Q277E/F230A A189H/K225S A134M/F351A T312K/F347I

I290L/Q108H Q277E/F230N A189H/A63I A134M/F351V T312K/V221F

I290L/F68V Q277E/ S87P A189H/A63P A134M/M157Y T312K/V221I

I290L/G100S Q277E/ S87Q A189H/I180L A134M/C44F T312K/G245S

I290L/G100T Q277E/L98H A189H/I180V A134M/C44Y T312K/Q92C

I290L/L323I Q277E/ S70K A189H/H151D A134M/I3L T312K/Q92S

I290L/L323M Q277E/F351A A189H/T220I A134M/I3M T312K/F230A

I290L/Q277D Q277E/F351V A189H/T220S V359E/V359K T312K/F230N

I290L/Q277E Q277E/M157Y A189H/L246I V359E/ S333A T312K/ S87P

I290L/C269N Q277E/C44F A189H/A272P V359E/ S333E T312K/ S87Q

I290L/C269T Q277E/C44Y A189H/ S353E V359E/T352D T312K/L98H

I290L/A326F Q277E/I3L A189H/ S353K V359E/T352E T312K/ S70K

I290L/A326I Q277E/I3M A189H/A256D V359E/M157F T312K/F351A

I290L/L152F C269N/C269T A189H/A256E V359E/M157S T312K/F351V

I290L/C282N C269N/A326F A189H/R224L V359E/D14G T312K/M157Y

I290L/ S329P C269N/A326I A189H/A134M V359E/D296A T312K/C44F

I290L/I45D C269N/L152F A189H/V359E V359E/D296L T312K/C44Y

I290L/I45L C269N/C282N A189H/V359K V359E/T314A T312K/I3L

I290L/E258A C269N/ S329P A189H/ S333A V359E/T314E T312K/I3M

I290L/A272E C269N/I45D A189H/ S333E V359E/F267Y T312N/L241V

I290L/T312A C269N/I45L A189H/T352D V359E/E71N T312N/V255I

I290L/T312R C269N/E258A A189H/T352E V359E/E252Q T312N/F344G

I290L/M327Q C269N/A272E A189H/M157F V359E/I367V T312N/I76L

I290L/M327T C269N/T312A A189H/M157S V359E/A31M T312N/I76M

I290L/N174Y C269N/T312R A189H/D14G V359E/A31 S T312N/G138K

I290L/L340I C269N/M327Q A189H/D296A V359E/F93A T312N/L238F

I290L/L340M C269N/M327T A189H/D296L V359E/L323C T312N/L238T

I290L/A189H C269N/N174Y A189H/T314A V359E/L323V T312N/I35L

I290L/A189Y C269N/L340I A189H/T314E V359E/T83G T312N/I35V Positions Positions Positions Positions Positions

I290L/N194R C269N/L340M A189H/F267Y V359E/T83N T312N/C208A

I290L/N194S C269N/A189H A189H/E71N V359E/Q92R T312N/C208S

I290L/L169V C269N/A189Y A189H/E252Q V359E/F267I T312N/E240A

I290L/K225D C269N/N194R A189H/I367V V359E/F267Q T312N/E240T

I290L/K225S C269N/N194S A189H/A31M V359E/E4K T312N/N148H

I290L/A63I C269N/L169V A189H/A31 S V359E/E90D T312N/F94L

I290L/A63P C269N/K225D A189H/F93A V359E/T312K T312N/F94Y

I290L/I180L C269N/K225S A189H/L323C V359E/T312N T312N/V150L

I290L/I180V C269N/A63I A189H/L323V V359E/L241V T312N/F68P

I290L/H151D C269N/A63P A189H/T83G V359E/V255I T312N/N148R

I290L/T220I C269N/I180L A189H/T83N V359E/F344G T312N/K361R

I290L/T220S C269N/I180V A189H/Q92R V359E/I76L T312N/Q280E

I290L/L246I C269N/H151D A189H/F267I V359E/I76M T312N/Q280R

I290L/A272P C269N/T220I A189H/F267Q V359E/G138K T312N/K225E

I290L/ S353E C269N/T220S A189H/E4K V359E/L238F T312N/K225G

I290L/ S353K C269N/L246I A189H/E90D V359E/L238T T312N/L238A

I290L/A256D C269N/A272P A189H/T312K V359E/I35L T312N/L238S

I290L/A256E C269N/ S353E A189H/T312N V359E/I35V T312N/C269A

I290L/R224L C269N/ S353K A189H/L241V V359E/C208A T312N/C269I

I290L/A134M C269N/A256D A189H/V255I V359E/C208S T312N/D296P

I290L/V359E C269N/A256E A189H/F344G V359E/E240A T312N/F140Y

I290L/V359K C269N/R224L A189H/I76L V359E/E240T T312N/I24L

I290L/ S333A C269N/A134M A189H/I76M V359E/N148H T312N/I24V

I290L/ S333E C269N/V359E A189H/G138K V359E/F94L T312N/D170S

I290L/T352D C269N/V359K A189H/L238F V359E/F94Y T312N/V229M

I290L/T352E C269N/ S333A A189H/L238T V359E/V150L T312N/E360A

I290L/M157F C269N/ S333E A189H/I35L V359E/F68P T312N/ S322V

I290L/M157S C269N/T352D A189H/I35V V359E/N148R T312N/F347I

I290L/D14G C269N/T352E A189H/C208A V359E/K361R T312N/V221F

I290L/D296A C269N/M157F A189H/C208S V359E/Q280E T312N/V221I

I290L/D296L C269N/M157S A189H/E240A V359E/Q280R T312N/G245S

I290L/T314A C269N/D14G A189H/E240T V359E/K225E T312N/Q92C

I290L/T314E C269N/D296A A189H/N148H V359E/K225G T312N/Q92S

I290L/F267Y C269N/D296L A189H/F94L V359E/L238A T312N/F230A

I290L/E71N C269N/T314A A189H/F94Y V359E/L238S T312N/F230N

I290L/E252Q C269N/T314E A189H/V150L V359E/C269A T312N/ S87P

I290L/I367V C269N/F267Y A189H/F68P V359E/C269I T312N/ S87Q

I290L/A31M C269N/E71N A189H/N148R V359E/D296P T312N/L98H

I290L/A31 S C269N/E252Q A189H/K361R V359E/F140Y T312N/ S70K

I290L/F93A C269N/I367V A189H/Q280E V359E/I24L T312N/F351A

I290L/L323C C269N/A31M A189H/Q280R V359E/I24V T312N/F351V

I290L/L323V C269N/A31 S A189H/K225E V359E/D170S T312N/M157Y Positions Positions Positions Positions Positions

I290L/T83G C269N/F93A A189H/K225G V359E/V229M T312N/C44F

I290L/T83N C269N/L323C A189H/L238A V359E/E360A T312N/C44Y

I290L/Q92R C269N/L323V A189H/L238S V359E/ S322V T312N/I3L

I290L/F267I C269N/T83G A189H/C269A V359E/F347I T312N/I3M

I290L/F267Q C269N/T83N A189H/C269I V359E/V221F L241V/V255I

I290L/E4K C269N/Q92R A189H/D296P V359E/V221I L241V/F344G

I290L/E90D C269N/F267I A189H/F140Y V359E/G245S L241V/I76L

I290L/T312K C269N/F267Q A189H/I24L V359E/Q92C L241V/I76M

I290L/T312N C269N/E4K A189H/I24V V359E/Q92S L241V/G138K

I290L/L241V C269N/E90D A189H/D170S V359E/F230A L241V/L238F

I290L/V255I C269N/T312K A189H/V229M V359E/F230N L241V/L238T

I290L/F344G C269N/T312N A189H/E360A V359E/ S87P L241V/I35L

I290L/I76L C269N/L241V A189H/ S322V V359E/ S87Q L241V/I35V

I290L/I76M C269N/V255I A189H/F347I V359E/L98H L241V/C208A

I290L/G138K C269N/F344G A189H/V221F V359E/ S70K L241V/C208S

I290L/L238F C269N/I76L A189H/V221I V359E/F351A L241V/E240A

I290L/L238T C269N/I76M A189H/G245S V359E/F351V L241V/E240T

I290L/I35L C269N/G138K A189H/Q92C V359E/M157Y L241V/N148H

I290L/I35V C269N/L238F A189H/Q92S V359E/C44F L241V/F94L

I290L/C208A C269N/L238T A189H/F230A V359E/C44Y L241V/F94Y

I290L/C208S C269N/I35L A189H/F230N V359E/I3L L241V/V150L

I290L/E240A C269N/I35V A189H/ S87P V359E/I3M L241V/F68P

I290L/E240T C269N/C208A A189H/ S87Q V359K/ S333A L241V/N148R

I290L/N148H C269N/C208S A189H/L98H V359K/ S333E L241V/K361R

I290L/F94L C269N/E240A A189H/ S70K V359K/T352D L241V/Q280E

I290L/F94Y C269N/E240T A189H/F351A V359K/T352E L241V/Q280R

I290L/V150L C269N/N148H A189H/F351V V359K/M157F L241V/K225E

I290L/F68P C269N/F94L A189H/M157Y V359K/M157S L241V/K225G

I290L/N148R C269N/F94Y A189H/C44F V359K/D14G L241V/L238A

I290L/K361R C269N/V150L A189H/C44Y V359K/D296A L241V/L238S

I290L/Q280E C269N/F68P A189H/I3L V359K/D296L L241V/C269A

I290L/Q280R C269N/N148R A189H/I3M V359K/T314A L241V/C269I

I290L/K225E C269N/K361R A189Y/N194R V359K/T314E L241V/D296P

I290L/K225G C269N/Q280E A189Y/N194S V359K/F267Y L241V/F140Y

I290L/L238A C269N/Q280R A189Y/L169V V359K/E71N L241V/I24L

I290L/L238S C269N/K225E A189Y/K225D V359K/E252Q L241V/I24V

I290L/C269A C269N/K225G A189Y/K225S V359K/I367V L241V/D170S

I290L/C269I C269N/L238A A189Y/A63I V359K/A31M L241V/V229M

I290L/D296P C269N/L238S A189Y/A63P V359K/A31 S L241V/E360A

I290L/F140Y C269N/C269A A189Y/I180L V359K/F93A L241V/ S322V

I290L/I24L C269N/C269I A189Y/I180V V359K/L323C L241V/F347I

I290L/I24V C269N/D296P A189Y/H151D V359K/L323V L241V/V221F Positions Positions Positions Positions Positions

I290L/D170S C269N/F140Y A189Y/T220I V359K/T83G L241V/V221I

I290L/V229M C269N/I24L A189Y/T220S V359K/T83N L241V/G245S

I290L/E360A C269N/I24V A189Y/L246I V359K/Q92R L241V/Q92C

I290L/ S322V C269N/D170S A189Y/A272P V359K/F267I L241V/Q92S

I290L/F347I C269N/V229M A189Y/ S353E V359K/F267Q L241V/F230A

I290L/V221F C269N/E360A A189Y/ S353K V359K/E4K L241V/F230N

I290L/V221I C269N/ S322V A189Y/A256D V359K/E90D L241V/ S87P

I290L/G245S C269N/F347I A189Y/A256E V359K/T312K L241V/ S87Q

I290L/Q92C C269N/V221F A189Y/R224L V359K/T312N L241V/L98H

I290L/Q92S C269N/V221I A189Y/A134M V359K/L241V L241V/ S70K

I290L/F230A C269N/G245S A189Y/V359E V359K/V255I L241V/F351A

I290L/F230N C269N/Q92C A189Y/V359K V359K/F344G L241V/F351V

I290L/ S87P C269N/Q92S A189Y/ S333A V359K/I76L L241V/M157Y

I290L/ S87Q C269N/F230A A189Y/ S333E V359K/I76M L241V/C44F

I290L/L98H C269N/F230N A189Y/T352D V359K/G138K L241V/C44Y

I290L/ S70K C269N/ S87P A189Y/T352E V359K/L238F L241V/I3L

I290L/F351A C269N/ S87Q A189Y/M157F V359K/L238T L241V/I3M

I290L/F351V C269N/L98H A189Y/M157S V359K/I35L V255I/F344G

I290L/M157Y C269N/ S70K A189Y/D14G V359K/I35V V255I/I76L

I290L/C44F C269N/F351A A189Y/D296A V359K/C208A V255I/I76M

I290L/C44Y C269N/F351V A189Y/D296L V359K/C208S V255I/G138K

I290L/I3L C269N/M157Y A189Y/T314A V359K/E240A V255I/L238F

I290L/I3M C269N/C44F A189Y/T314E V359K/E240T V255I/L238T

I290M/L330M C269N/C44Y A189Y/F267Y V359K/N148H V255I/I35L

I290M/H131C C269N/I3L A189Y/E71N V359K/F94L V255I/I35V

I290M/A189G C269N/I3M A189Y/E252Q V359K/F94Y V255I/C208A

I290M/Q193K C269T/A326F A189Y/I367V V359K/V150L V255I/C208S

I290M/Q193R C269T/A326I A189Y/A31M V359K/F68P V255I/E240A

I290M/L242I C269T/L152F A189Y/A31 S V359K/N148R V255I/E240T

I290M/Q108H C269T/C282N A189Y/F93A V359K/K361R V255I/N148H

I290M/F68V C269T/ S329P A189Y/L323C V359K/Q280E V255I/F94L

I290M/G100S C269T/I45D A189Y/L323V V359K/Q280R V255I/F94Y

I290M/G100T C269T/I45L A189Y/T83G V359K/K225E V255I/V150L

I290M/L323I C269T/E258A A189Y/T83N V359K/K225G V255I/F68P

I290M/L323M C269T/A272E A189Y/Q92R V359K/L238A V255I/N148R

I290M/Q277D C269T/T312A A189Y/F267I V359K/L238S V255I/K361R

I290M/Q277E C269T/T312R A189Y/F267Q V359K/C269A V255I/Q280E

I290M/C269N C269T/M327Q A189Y/E4K V359K/C269I V255I/Q280R

I290M/C269T C269T/M327T A189Y/E90D V359K/D296P V255I/K225E

I290M/A326F C269T/N174Y A189Y/T312K V359K/F140Y V255I/K225G

I290M/A326I C269T/L340I A189Y/T312N V359K/I24L V255I/L238A

I290M/L152F C269T/L340M A189Y/L241V V359K/I24V V255I/L238S Positions Positions Positions Positions Positions

I290M/C282N C269T/A189H A189Y/V255I V359K/D170S V255I/C269A

I290M/ S329P C269T/A189Y A189Y/F344G V359K/V229M V255I/C269I

I290M/I45D C269T/N194R A189Y/I76L V359K/E360A V255I/D296P

I290M/I45L C269T/N194S A189Y/I76M V359K/ S322V V255I/F140Y

I290M/E258A C269T/L169V A189Y/G138K V359K/F347I V255I/I24L

I290M/A272E C269T/K225D A189Y/L238F V359K/V221F V255I/I24V

I290M/T312A C269T/K225S A189Y/L238T V359K/V221I V255I/D170S

I290M/T312R C269T/A63I A189Y/I35L V359K/G245S V255I/V229M

I290M/M327Q C269T/A63P A189Y/I35V V359K/Q92C V255I/E360A

I290M/M327T C269T/I180L A189Y/C208A V359K/Q92S V255I/ S322V

I290M/N174Y C269T/I180V A189Y/C208S V359K/F230A V255I/F347I

I290M/L340I C269T/H151D A189Y/E240A V359K/F230N V255I/V221F

I290M/L340M C269T/T220I A189Y/E240T V359K/ S87P V255I/V221I

I290M/A189H C269T/T220S A189Y/N148H V359K/ S87Q V255I/G245S

I290M/A189Y C269T/L246I A189Y/F94L V359K/L98H V255I/Q92C

I290M/N194R C269T/A272P A189Y/F94Y V359K/ S70K V255I/Q92S

I290M/N194S C269T/ S353E A189Y/V150L V359K/F351A V255I/F230A

I290M/L169V C269T/ S353K A189Y/F68P V359K/F351V V255I/F230N

I290M/K225D C269T/A256D A189Y/N148R V359K/M157Y V255I/ S87P

I290M/K225S C269T/A256E A189Y/K361R V359K/C44F V255I/ S87Q

I290M/A63I C269T/R224L A189Y/Q280E V359K/C44Y V255I/L98H

I290M/A63P C269T/A134M A189Y/Q280R V359K/I3L V255I/ S70K

I290M/I180L C269T/V359E A189Y/K225E V359K/I3M V255I/F351A

I290M/I180V C269T/V359K A189Y/K225G S333A/ S333E V255I/F351V

I290M/H151D C269T/ S333A A189Y/L238A S333A/T352D V255I/M157Y

I290M/T220I C269T/ S333E A189Y/L238S S333A/T352E V255I/C44F

I290M/T220S C269T/T352D A189Y/C269A S333A/M157F V255I/C44Y

I290M/L246I C269T/T352E A189Y/C269I S333A/M157S V255I/I3L

I290M/A272P C269T/M157F A189Y/D296P S333A/D14G V255I/I3M

I290M/ S353E C269T/M157S A189Y/F140Y S333A/D296A F344G/I76L

I290M/ S353K C269T/D14G A189Y/I24L S333A/D296L F344G/I76M

I290M/A256D C269T/D296A A189Y/I24V S333A/T314A F344G/G138K

I290M/A256E C269T/D296L A189Y/D170S S333A/T314E F344G/L238F

I290M/R224L C269T/T314A A189Y/V229M S333A/F267Y F344G/L238T

I290M/A134M C269T/T314E A189Y/E360A S333A/E71N F344G/I35L

I290M/V359E C269T/F267Y A189Y/ S322V S333A/E252Q F344G/I35V

I290M/V359K C269T/E71N A189Y/F347I S333A/I367V F344G/C208A

I290M/ S333A C269T/E252Q A189Y/V221F S333A/A31M F344G/C208S

I290M/ S333E C269T/I367V A189Y/V221I S333A/A31 S F344G/E240A

I290M/T352D C269T/A31M A189Y/G245S S333A/F93A F344G/E240T

I290M/T352E C269T/A31 S A189Y/Q92C S333A/L323C F344G/N148H

I290M/M157F C269T/F93A A189Y/Q92S S333A/L323V F344G/F94L Positions Positions Positions Positions Positions

I290M/M157S C269T/L323C A189Y/F230A S333A/T83G F344G/F94Y

I290M/D14G C269T/L323V A189Y/F230N S333A/T83N F344G/V150L

I290M/D296A C269T/T83G A189Y/ S87P S333A/Q92R F344G/F68P

I290M/D296L C269T/T83N A189Y/ S87Q S333A/F267I F344G/N148R

I290M/T314A C269T/Q92R A189Y/L98H S333A/F267Q F344G/K361R

I290M/T314E C269T/F267I A189Y/ S70K S333A/E4K F344G/Q280E

I290M/F267Y C269T/F267Q A189Y/F351A S333A/E90D F344G/Q280R

I290M/E71N C269T/E4K A189Y/F351V S333A/T312K F344G/K225E

I290M/E252Q C269T/E90D A189Y/M157Y S333A/T312N F344G/K225G

I290M/I367V C269T/T312K A189Y/C44F S333A/L241V F344G/L238A

I290M/A31M C269T/T312N A189Y/C44Y S333A/V255I F344G/L238S

I290M/A31 S C269T/L241V A189Y/I3L S333A/F344G F344G/C269A

I290M/F93A C269T/V255I A189Y/I3M S333A/I76L F344G/C269I

I290M/L323C C269T/F344G N194R/N194S S333A/I76M F344G/D296P

I290M/L323V C269T/I76L N194R/L169V S333A/G138K F344G/F140Y

I290M/T83G C269T/I76M N194R/K225D S333A/L238F F344G/I24L

I290M/T83N C269T/G138K N194R/K225S S333A/L238T F344G/I24V

I290M/Q92R C269T/L238F N194R/A63I S333A/I35L F344G/D170S

I290M/F267I C269T/L238T N194R/A63P S333A/I35V F344G/V229M

I290M/F267Q C269T/I35L N194R/I180L S333A/C208A F344G/E360A

I290M/E4K C269T/I35V N194R/I180V S333A/C208S F344G/ S322V

I290M/E90D C269T/C208A N194R/H151D S333A/E240A F344G/F347I

I290M/T312K C269T/C208S N194R/T220I S333A/E240T F344G/V221F

I290M/T312N C269T/E240A N194R/T220S S333A/N148H F344G/V221I

I290M/L241V C269T/E240T N194R/L246I S333A/F94L F344G/G245S

I290M/V255I C269T/N148H N194R/A272P S333A/F94Y F344G/Q92C

I290M/F344G C269T/F94L N194R/ S353E S333A/V150L F344G/Q92S

I290M/I76L C269T/F94Y N194R/ S353K S333A/F68P F344G/F230A

I290M/I76M C269T/V150L N194R/A256D S333A/N148R F344G/F230N

I290M/G138K C269T/F68P N194R/A256E S333A/K361R F344G/ S87P

I290M/L238F C269T/N148R N194R/R224L S333A/Q280E F344G/ S87Q

I290M/L238T C269T/K361R N194R/A134M S333A/Q280R F344G/L98H

I290M/I35L C269T/Q280E N194R/V359E S333A/K225E F344G/ S70K

I290M/I35V C269T/Q280R N194R/V359K S333A/K225G F344G/F351A

I290M/C208A C269T/K225E N194R/ S333A S333A/L238A F344G/F351V

I290M/C208S C269T/K225G N194R/ S333E S333A/L238S F344G/M157Y

I290M/E240A C269T/L238A N194R/T352D S333A/C269A F344G/C44F

I290M/E240T C269T/L238S N194R/T352E S333A/C269I F344G/C44Y

I290M/N148H C269T/C269A N194R/M157F S333A/D296P F344G/I3L

I290M/F94L C269T/C269I N194R/M157S S333A/F140Y F344G/I3M

I290M/F94Y C269T/D296P N194R/D14G S333A/I24L I76L/I76M

I290M/V150L C269T/F140Y N194R/D296A S333A/I24V I76L/G138K Positions Positions Positions Positions Positions

I290M/F68P C269T/I24L N194R/D296L S333A/D170S I76L/L238F

I290M/N148R C269T/I24V N194R/T314A S333A/V229M I76L/L238T

I290M/K361R C269T/D170S N194R/T314E S333A/E360A I76L/I35L

I290M/Q280E C269T/V229M N194R/F267Y S333A/ S322V I76L/I35V

I290M/Q280R C269T/E360A N194R/E71N S333A/F347I I76L/C208A

I290M/K225E C269T/ S322V N194R/E252Q S333A/V221F I76L/C208S

I290M/K225G C269T/F347I N194R/I367V S333A/V221I I76L/E240A

I290M/L238A C269T/V221F N194R/A31M S333A/G245S I76L/E240T

I290M/L238S C269T/V221I N194R/A31S S333A/Q92C I76L/N148H

I290M/C269A C269T/G245S N194R/F93A S333A/Q92S I76L/F94L

I290M/C269I C269T/Q92C N194R/L323C S333A/F230A I76L/F94Y

I290M/D296P C269T/Q92S N194R/L323V S333A/F230N I76L/V150L

I290M/F140Y C269T/F230A N194R/T83G S333A/ S87P I76L/F68P

I290M/I24L C269T/F230N N194R/T83N S333A/ S87Q I76L/N148R

I290M/I24V C269T/ S87P N194R/Q92R S333A/L98H I76L/K361R

I290M/D170S C269T/ S87Q N194R/F267I S333A/ S70K I76L/Q280E

I290M/V229M C269T/L98H N194R/F267Q S333A/F351A I76L/Q280R

I290M/E360A C269T/ S70K N194R/E4K S333A/F351V I76L/K225E

I290M/ S322V C269T/F351A N194R/E90D S333A/M157Y I76L/K225G

I290M/F347I C269T/F351V N194R/T312K S333A/C44F I76L/L238A

I290M/V221F C269T/M157Y N194R/T312N S333A/C44Y I76L/L238S

I290M/V221I C269T/C44F N194R/L241V S333A/I3L I76L/C269A

I290M/G245S C269T/C44Y N194R/V255I S333A/I3M I76L/C269I

I290M/Q92C C269T/I3L N194R/F344G S333E/T352D I76L/D296P

I290M/Q92S C269T/I3M N194R/I76L S333E/T352E I76L/F140Y

I290M/F230A A326F/A326I N194R/I76M S333E/M157F I76L/I24L

I290M/F230N A326F/L152F N194R/G138K S333E/M157S I76L/I24V

I290M/ S87P A326F/C282N N194R/L238F S333E/D14G I76L/D170S

I290M/ S87Q A326F/ S329P N194R/L238T S333E/D296A I76L/V229M

I290M/L98H A326F/I45D N194R/I35L S333E/D296L I76L/E360A

I290M/ S70K A326F/I45L N194R/I35V S333E/T314A I76L/ S322V

I290M/F351A A326F/E258A N194R/C208A S333E/T314E I76L/F347I

I290M/F351V A326F/A272E N194R/C208S S333E/F267Y I76L/V221F

I290M/M157Y A326F/T312A N194R/E240A S333E/E71N I76L/V221I

I290M/C44F A326F/T312R N194R/E240T S333E/E252Q I76L/G245S

I290M/C44Y A326F/M327Q N194R/N148H S333E/I367V I76L/Q92C

I290M/I3L A326F/M327T N194R/F94L S333E/A31M I76L/Q92S

I290M/I3M A326F/N174Y N194R/F94Y S333E/A31 S I76L/F230A

L330M/H131C A326F/L340I N194R/V150L S333E/F93A I76L/F230N

L330M/A189G A326F/L340M N194R/F68P S333E/L323C I76L/ S87P

L330M/Q193K A326F/A189H N194R/N148R S333E/L323V I76L/ S87Q

L330M/Q193R A326F/A189Y N194R/K361R S333E/T83G I76L/L98H Positions Positions Positions Positions Positions

L330M/L242I A326F/N194R N194R/Q280E S333E/T83N I76L/ S70K

L330M/Q108H A326F/N194S N194R/Q280R S333E/Q92R I76L/F351A

L330M/F68V A326F/L169V N194R/K225E S333E/F267I I76L/F351V

L330M/G100S A326F/K225D N194R/K225G S333E/F267Q I76L/M157Y

L330M/G100T A326F/K225S N194R/L238A S333E/E4K I76L/C44F

L330M/L323I A326F/A63I N194R/L238S S333E/E90D I76L/C44Y

L330M/L323M A326F/A63P N194R/C269A S333E/T312K I76L/I3L

L330M/Q277D A326F/I180L N194R/C269I S333E/T312N I76L/I3M

L330M/Q277E A326F/I180V N194R/D296P S333E/L241V I76M/G138K

L330M/C269N A326F/H151D N194R/F140Y S333E/V255I I76M/L238F

L330M/C269T A326F/T220I N194R/I24L S333E/F344G I76M/L238T

L330M/A326F A326F/T220S N194R/I24V S333E/I76L I76M/I35L

L330M/A326I A326F/L246I N194R/D170S S333E/I76M I76M/I35V

L330M/L152F A326F/A272P N194R/V229M S333E/G138K I76M/C208A

L330M/C282N A326F/ S353E N194R/E360A S333E/L238F I76M/C208S

L330M/ S329P A326F/ S353K N194R/ S322V S333E/L238T I76M/E240A

L330M/I45D A326F/A256D N194R/F347I S333E/I35L I76M/E240T

L330M/I45L A326F/A256E N194R/V221F S333E/I35V I76M/N148H

L330M/E258A A326F/R224L N194R/V221I S333E/C208A I76M/F94L

L330M/A272E A326F/A134M N194R/G245S S333E/C208S I76M/F94Y

L330M/T312A A326F/V359E N194R/Q92C S333E/E240A I76M/V150L

L330M/T312R A326F/V359K N194R/Q92S S333E/E240T I76M/F68P

L330M/M327Q A326F/ S333A N194R/F230A S333E/N148H I76M/N148R

L330M/M327T A326F/ S333E N194R/F230N S333E/F94L I76M/K361R

L330M/N174Y A326F/T352D N194R/ S87P S333E/F94Y I76M/Q280E

L330M/L340I A326F/T352E N194R/ S87Q S333E/V150L I76M/Q280R

L330M/L340M A326F/M157F N194R/L98H S333E/F68P I76M/K225E

L330M/A189H A326F/M157S N194R/ S70K S333E/N148R I76M/K225G

L330M/A189Y A326F/D14G N194R/F351A S333E/K361R I76M/L238A

L330M/N194R A326F/D296A N194R/F351V S333E/Q280E I76M/L238S

L330M/N194S A326F/D296L N194R/M157Y S333E/Q280R I76M/C269A

L330M/L169V A326F/T314A N194R/C44F S333E/K225E I76M/C269I

L330M/K225D A326F/T314E N194R/C44Y S333E/K225G I76M/D296P

L330M/K225S A326F/F267Y N194R/I3L S333E/L238A I76M/F140Y

L330M/A63I A326F/E71N N194R/I3M S333E/L238S I76M/I24L

L330M/A63P A326F/E252Q N194S /L169V S333E/C269A I76M/I24V

L330M/I180L A326F/I367V N194S /K225D S333E/C269I I76M/D170S

L330M/I180V A326F/A31M N194S /K225S S333E/D296P I76M/V229M

L330M/H151D A326F/A31 S N194S /A63I S333E/F140Y I76M/E360A

L330M/T220I A326F/F93A N194S /A63P S333E/I24L I76M/ S322V

L330M/T220S A326F/L323C N194S /I180L S333E/I24V I76M/F347I

L330M/L246I A326F/L323V N194S /I180V S333E/D170S I76M/V221F Positions Positions Positions Positions Positions

L330M/A272P A326F/T83G N194S/H151D S333E/V229M I76M/V221I

L330M/S353E A326F/T83N N194S/T220I S333E/E360A I76M/G245S

L330M/S353K A326F/Q92R N194S/T220S S333E/S322V I76M/Q92C

L330M/A256D A326F/F267I N194S/L246I S333E/F347I I76M/Q92S

L330M/A256E A326F/F267Q N194S/A272P S333E/V221F I76M/F230A

L330M/R224L A326F/E4K N194S/S353E S333E/V221I I76M/F230N

L330M/A134M A326F/E90D N194S/S353K S333E/G245S I76M/S87P

L330M/V359E A326F/T312K N194S/A256D S333E/Q92C I76M/S87Q

L330M/V359K A326F/T312N N194S/A256E S333E/Q92S I76M/L98H

L330M/S333A A326F/L241V N194S/R224L S333E/F230A I76M/S70K

L330M/S333E A326F/V255I N194S/A134M S333E/F230N I76M/F351A

L330M/T352D A326F/F344G N194S/V359E S333E/S87P I76M/F351V

L330M/T352E A326F/I76L N194S/V359K S333E/S87Q I76M/M157Y

L330M/M157F A326F/I76M N194S/S333A S333E/L98H I76M/C44F

L330M/M157S A326F/G138K N194S/S333E S333E/S70K I76M/C44Y

L330M/D14G A326F/L238F N194S/T352D S333E/F351A I76M/I3L

L330M/D296A A326F/L238T N194S/T352E S333E/F351V I76M/I3M

L330M/D296L A326F/I35L N194S/M157F S333E/M157Y G138K/L238F

L330M/T314A A326F/I35V N194S/M157S S333E/C44F G138K/L238T

L330M/T314E A326F/C208A N194S/D14G S333E/C44Y G138K/I35L

L330M/F267Y A326F/C208S N194S/D296A S333E/I3L G138K/I35V

L330M/E71N A326F/E240A N194S/D296L S333E/I3M G138K/C208A

L330M/E252Q A326F/E240T N194S/T314A T352D/T352E G138K/C208S

L330M/I367V A326F/N148H N194S/T314E T352D/M157F G138K/E240A

L330M/A31M A326F/F94L N194S/F267Y T352D/M157S G138K/E240T

L330M/A31S A326F/F94Y N194S/E71N T352D/D14G G138K/N148H

L330M/F93A A326F/V150L N194S/E252Q T352D/D296A G138K/F94L

L330M/L323C A326F/F68P N194S/I367V T352D/D296L G138K/F94Y

L330M/L323V A326F/N148R N194S/A31M T352D/T314A G138K/V150L

L330M/T83G A326F/K361R N194S/A31S T352D/T314E G138K/F68P

L330M/T83N A326F/Q280E N194S/F93A T352D/F267Y G138K/N148R

L330M/Q92R A326F/Q280R N194S/L323C T352D/E71N G138K/K361R

L330M/F267I A326F/K225E N194S/L323V T352D/E252Q G138K/Q280E

L330M/F267Q A326F/K225G N194S/T83G T352D/I367V G138K/Q280R

L330M/E4K A326F/L238A N194S/T83N T352D/A31M G138K/K225E

L330M/E90D A326F/L238S N194S/Q92R T352D/A31S G138K/K225G

L330M/T312K A326F/C269A N194S/F267I T352D/F93A G138K/L238A

L330M/T312N A326F/C269I N194S/F267Q T352D/L323C G138K/L238S

L330M/L241V A326F/D296P N194S/E4K T352D/L323V G138K/C269A

L330M/V255I A326F/F140Y N194S/E90D T352D/T83G G138K/C269I

L330M/F344G A326F/I24L N194S/T312K T352D/T83N G138K/D296P

L330M/I76L A326F/I24V N194S/T312N T352D/Q92R G138K/F140Y Positions Positions Positions Positions Positions

L330M/I76M A326F/D170S N194S/L241V T352D/F267I G138K/I24L

L330M/G138K A326F/V229M N194S/V255I T352D/F267Q G138K/I24V

L330M/L238F A326F/E360A N194S/F344G T352D/E4K G138K/D170S

L330M/L238T A326F/S322V N194S/I76L T352D/E90D G138K/V229M

L330M/I35L A326F/F347I N194S/I76M T352D/T312K G138K/E360A

L330M/I35V A326F/V221F N194S/G138K T352D/T312N G138K/S322V

L330M/C208A A326F/V221I N194S/L238F T352D/L241V G138K/F347I

L330M/C208S A326F/G245S N194S/L238T T352D/V255I G138K/V221F

L330M/E240A A326F/Q92C N194S/I35L T352D/F344G G138K/V221I

L330M/E240T A326F/Q92S N194S/I35V T352D/I76L G138K/G245S

L330M/N148H A326F/F230A N194S/C208A T352D/I76M G138K/Q92C

L330M/F94L A326F/F230N N194S/C208S T352D/G138K G138K/Q92S

L330M/F94Y A326F/S87P N194S/E240A T352D/L238F G138K/F230A

L330M/V150L A326F/S87Q N194S/E240T T352D/L238T G138K/F230N

L330M/F68P A326F/L98H N194S/N148H T352D/I35L G138K/S87P

L330M/N148R A326F/S70K N194S/F94L T352D/I35V G138K/S87Q

L330M/K361R A326F/F351A N194S/F94Y T352D/C208A G138K/L98H

L330M/Q280E A326F/F351V N194S/V150L T352D/C208S G138K/S70K

L330M/Q280R A326F/M157Y N194S/F68P T352D/E240A G138K/F351A

L330M/K225E A326F/C44F N194S/N148R T352D/E240T G138K/F351V

L330M/K225G A326F/C44Y N194S/K361R T352D/N148H G138K/M157Y

L330M/L238A A326F/I3L N194S/Q280E T352D/F94L G138K/C44F

L330M/L238S A326F/I3M N194S/Q280R T352D/F94Y G138K/C44Y

L330M/C269A A326I/L152F N194S/K225E T352D/V150L G138K/I3L

L330M/C269I A326I/C282N N194S/K225G T352D/F68P G138K/I3M

L330M/D296P A326I/S329P N194S/L238A T352D/N148R L238F/L238T

L330M/F140Y A326I/I45D N194S/L238S T352D/K361R L238F/I35L

L330M/I24L A326I/I45L N194S/C269A T352D/Q280E L238F/I35V

L330M/I24V A326I/E258A N194S/C269I T352D/Q280R L238F/C208A

L330M/D170S A326I/A272E N194S/D296P T352D/K225E L238F/C208S

L330M/V229M A326I/T312A N194S/F140Y T352D/K225G L238F/E240A

L330M/E360A A326I/T312R N194S/I24L T352D/L238A L238F/E240T

L330M/S322V A326I/M327Q N194S/I24V T352D/L238S L238F/N148H

L330M/F347I A326I/M327T N194S/D170S T352D/C269A L238F/F94L

L330M/V221F A326I/N174Y N194S/V229M T352D/C269I L238F/F94Y

L330M/V221I A326I/L340I N194S/E360A T352D/D296P L238F/V150L

L330M/G245S A326I/L340M N194S/S322V T352D/F140Y L238F/F68P

L330M/Q92C A326I/A189H N194S/F347I T352D/I24L L238F/N148R

L330M/Q92S A326I/A189Y N194S/V221F T352D/I24V L238F/K361R

L330M/F230A A326I/N194R N194S/V221I T352D/D170S L238F/Q280E

L330M/F230N A326I/N194S N194S/G245S T352D/V229M L238F/Q280R

L330M/S87P A326I/L169V N194S/Q92C T352D/E360A L238F/K225E Positions Positions Positions Positions Positions

L330M/ S87Q A326I/K225D N194S /Q92S T352D/ S322V L238F/K225G

L330M/L98H A326I/K225S N194S /F230A T352D /F347I L238F/L238A

L330M/ S70K A326I/A63I N194S /F230N T352D /V221F L238F/L238S

L330M/F351A A326I/A63P N194S / S87P T352D/V221I L238F/C269A

L330M/F351V A326I/I180L N194S / S87Q T352D /G245S L238F/C269I

L330M/M157Y A326I/I180V N194S /L98H T352D /Q92C L238F/D296P

L330M/C44F A326I/H151D N194S / S70K T352D/Q92S L238F/F140Y

L330M/C44Y A326I/T220I N194S /F351A T352D/F230A L238F/I24L

L330M/I3L A326I/T220S N194S /F351V T352D/F230N L238F/I24V

L330M/I3M A326I/L246I N194S /M157Y T352D/ S87P L238F/D170S

H131C/A189G A326I/A272P N194S /C44F T352D/ S87Q L238F/V229M

H131C/Q193K A326I/ S353E N194S /C44Y T352D/L98H L238F/E360A

H131C/Q193R A326I/ S353K N194S /I3L T352D/ S70K L238F/ S322V

H131C/L242I A326I/A256D N194S /I3M T352D/F351A L238F/F347I

H131C/Q108H A326I/A256E L169V/K225D T352D/F351V L238F/V221F

H131C/F68V A326I/R224L L169V/K225S T352D/M157Y L238F/V221I

H131C/G100S A326I/A134M L169V/A63I T352D /C44F L238F/G245S

H131C/G100T A326I/V359E L169V/A63P T352D /C44Y L238F/Q92C

H131C/L323I A326I/V359K L169V/I180L T352D /I3L L238F/Q92S

H131C/L323M A326I/ S333A L169V/I180V T352D/I3M L238F/F230A

H131C/Q277D A326I/ S333E L169V/H151D T352E/M157F L238F/F230N

H131C/Q277E A326I/T352D L169V/T220I T352E/M157S L238F/ S87P

H131C/C269N A326I/T352E L169V/T220S T352E/D14G L238F/ S87Q

H131C/C269T A326I/M157F L169V/L246I T352E/D296A L238F/L98H

H131C/A326F A326I/M157S L169V/A272P T352E/D296L L238F/ S70K

H131C/A326I A326I/D14G L169V/ S353E T352E/T314A L238F/F351A

H131C/L152F A326I/D296A L169V/ S353K T352E/T314E L238F/F351V

H131C/C282N A326I/D296L L169V/A256D T352E/F267Y L238F/M157Y

H131C/ S329P A326I/T314A L169V/A256E T352E/E71N L238F/C44F

H131C/I45D A326I/T314E L169V/R224L T352E/E252Q L238F/C44Y

H131C/I45L A326I/F267Y L169V/A134M T352E/I367V L238F/I3L

H131C/E258A A326I/E71N L169V/V359E T352E/A31M L238F/I3M

H131C/A272E A326I/E252Q L169V/V359K T352E/A31 S L238T/I35L

H131C/T312A A326I/I367V L169V/ S333A T352E/F93A L238T/I35V

H131C/T312R A326I/A31M L169V/ S333E T352E/L323C L238T/C208A

H131C/M327Q A326I/A31 S L169V/T352D T352E/L323V L238T/C208S

H131C/M327T A326I/F93A L169V/T352E T352E/T83G L238T/E240A

H131C/N174Y A326I/L323C L169V/M157F T352E/T83N L238T/E240T

H131C/L340I A326I/L323V L169V/M157S T352E/Q92R L238T/N148H

H131C/L340M A326I/T83G L169V/D14G T352E/F267I L238T/F94L

H131C/A189H A326I/T83N L169V/D296A T352E/F267Q L238T/F94Y

H131C/A189Y A326I/Q92R L169V/D296L T352E/E4K L238T/V150L Positions Positions Positions Positions Positions

H131C/N194R A326I/F267I L169V/T314A T352E/E90D L238T/F68P

H131C/N194S A326I/F267Q L169V/T314E T352E/T312K L238T/N148R

H131C/L169V A326I/E4K L169V/F267Y T352E/T312N L238T/K361R

H131C/K225D A326I/E90D L169V/E71N T352E/L241V L238T/Q280E

H131C/K225S A326I/T312K L169V/E252Q T352E/V255I L238T/Q280R

H131C/A63I A326I/T312N LI 69V/ 1367V T352E/F344G L238T/K225E

H131C/A63P A326I/L241V L169V/A31M T352E/I76L L238T/K225G

H131C/I180L A326I/V255I L169V/A31 S T352E/I76M L238T/L238A

H131C/I180V A326I/F344G L169V/F93A T352E/G138K L238T/L238S

H131C/H151D A326I/I76L L169V/L323C T352E/L238F L238T/C269A

H131C/T220I A326I/I76M L169V/L323V T352E/L238T L238T/C269I

H131C/T220S A326I/G138K L169V/T83G T352E/I35L L238T/D296P

H131C/L246I A326I/L238F L169V/T83N T352E/I35V L238T/F140Y

H131C/A272P A326I/L238T L169V/Q92R T352E/C208A L238T/I24L

H131C/ S353E A326I/I35L L169V/F267I T352E/C208S L238T/I24V

H131C/ S353K A326I/I35V L169V/F267Q T352E/E240A L238T/D170S

H131C/A256D A326I/C208A L169V/E4K T352E/E240T L238T/V229M

H131C/A256E A326I/C208S L169V/E90D T352E/N148H L238T/E360A

H131C/R224L A326I/E240A L169V/T312K T352E/F94L L238T/ S322V

H131C/A134M A326I/E240T L169V/T312N T352E/F94Y L238T/F347I

H131C/V359E A326I/N148H L169V/L241V T352E/V150L L238T/V221F

H131C/V359K A326I/F94L L169V/V255I T352E/F68P L238T/V221I

H131C/ S333A A326I/F94Y L169V/F344G T352E/N148R L238T/G245S

H131C/ S333E A326I/V150L L169V/I76L T352E/K361R L238T/Q92C

H131C/T352D A326I/F68P L169V/I76M T352E/Q280E L238T/Q92S

H131C/T352E A326I/N148R L169V/G138K T352E/Q280R L238T/F230A

H131C/M157F A326I/K361R L169V/L238F T352E/K225E L238T/F230N

H131C/M157S A326I/Q280E L169V/L238T T352E/K225G L238T/ S87P

H131C/D14G A326I/Q280R L169V/I35L T352E/L238A L238T/ S87Q

H131C/D296A A326I/K225E L169V/I35V T352E/L238S L238T/L98H

H131C/D296L A326I/K225G L169V/C208A T352E/C269A L238T/ S70K

H131C/T314A A326I/L238A L169V/C208S T352E/C269I L238T/F351A

H131C/T314E A326I/L238S L169V/E240A T352E/D296P L238T/F351V

H131C/F267Y A326I/C269A L169V/E240T T352E/F140Y L238T/M157Y

H131C/E71N A326I/C269I L169V/N148H T352E/I24L L238T/C44F

H131C/E252Q A326I/D296P L169V/F94L T352E/I24V L238T/C44Y

H131C/I367V A326I/F140Y L169V/F94Y T352E/D170S L238T/I3L

H131C/A31M A326I/I24L L169V/V150L T352E/V229M L238T/I3M

H131C/A31 S A326I/I24V L169V/F68P T352E/E360A I35L/I35V

H131C/F93A A326I/D170S L169V/N148R T352E/ S322V I35L/C208A

H131C/L323C A326I/V229M L169V/K361R T352E/F347I I35L/C208S

H131C/L323V A326I/E360A L169V/Q280E T352E/V221F I35L/E240A Positions Positions Positions Positions Positions

H131C/T83G A326I/ S322V L169V/Q280R T352E/V221I I35L/E240T

H131C/T83N A326I/F347I L169V/K225E T352E/G245S I35L/N148H

H131C/Q92R A326I/V221F L169V/K225G T352E/Q92C I35L/F94L

H131C/F267I A326I/V221I L169V/L238A T352E/Q92S I35L/F94Y

H131C/F267Q A326I/G245S L169V/L238S T352E/F230A I35L/V150L

H131C/E4K A326I/Q92C L169V/C269A T352E/F230N I35L/F68P

H131C/E90D A326I/Q92S L169V/C269I T352E/ S87P I35L/N148R

H131C/T312K A326I/F230A L169V/D296P T352E/ S87Q I35L/K361R

H131C/T312N A326I/F230N L169V/F140Y T352E/L98H I35L/Q280E

H131C/L241V A326I/ S87P L169V/I24L T352E/ S70K I35L/Q280R

H131C/V255I A326I/ S87Q L169V/I24V T352E/F351A I35L/K225E

H131C/F344G A326I/L98H L169V/D170S T352E/F351V I35L/K225G

H131C/I76L A326I/ S70K L169V/V229M T352E/M157Y I35L/L238A

H131C/I76M A326I/F351A L169V/E360A T352E/C44F I35L/L238S

H131C/G138K A326I/F351V L169V/ S322V T352E/C44Y I35L/C269A

H131C/L238F A326I/M157Y L169V/F347I T352E/I3L I35L/C269I

H131C/L238T A326I/C44F L169V/V221F T352E/I3M I35L/D296P

H131C/I35L A326I/C44Y L169V/V221I M157F/M157S I35L/F140Y

H131C/I35V A326I/I3L L169V/G245S M157F/D14G I35L/I24L

H131C/C208A A326I/I3M L169V/Q92C M157F/D296A I35L/I24V

H131C/C208S L152F/C282N L169V/Q92S M157F/D296L I35L/D170S

H131C/E240A L152F/ S329P L169V/F230A M157F/T314A I35L/V229M

H131C/E240T L152F/I45D L169V/F230N M157F/T314E I35L/E360A

H131C/N148H L152F/I45L L169V/ S87P M157F/F267Y I35L/ S322V

H131C/F94L L152F/E258A L169V/ S87Q M157F/E71N I35L/F347I

H131C/F94Y L152F/A272E L169V/L98H M157F/E252Q I35L/V221F

H131C/V150L L152F/T312A L169V/ S70K M157F/I367V I35L/V221I

H131C/F68P L152F/T312R L169V/F351A M157F/A31M I35L/G245S

H131C/N148R L152F/M327Q L169V/F351V M157F/A31 S I35L/Q92C

H131C/K361R L152F/M327T L169V/M157Y M157F/F93A I35L/Q92S

H131C/Q280E L152F/N174Y L169V/C44F M157F/L323C I35L/F230A

H131C/Q280R L152F/L340I L169V/C44Y M157F/L323V I35L/F230N

H131C/K225E L152F/L340M L169V/I3L M157F/T83G I35L/ S87P

H131C/K225G L152F/A189H L169V/I3M M157F/T83N I35L/ S87Q

H131C/L238A L152F/A189Y K225D/K225S M157F/Q92R I35L/L98H

H131C/L238S L152F/N194R K225D /A63I M157F/F267I I35L/ S70K

H131C/C269A L152F/N194S K225D /A63P M157F/F267Q I35L/F351A

H131C/C269I L152F/L169V K225D /I180L M157F/E4K I35L/F351V

H131C/D296P L152F/K225D K225D/I180V M157F/E90D I35L/M157Y

H131C/F140Y L152F/K225S K225D /H151D M157F/T312K I35L/C44F

H131C/I24L L152F/A63I K225D/T220I M157F/T312N I35L/C44Y

H131C/I24V L152F/A63P K225D/T220S M157F/L241V I35L/I3L Positions Positions Positions Positions Positions

H131C/D170S L152F/I180L K225D /L246I M157F/V255I I35L/I3M

H131C/V229M L152F/I180V K225D/A272P M157F/F344G I35V/C208A

H131C/E360A L152F/H151D K225D / S353E M157F/I76L I35V/C208S

H131C/ S322V L152F/T220I K225D/ S353K M157F/I76M I35V/E240A

H131C/F347I L152F/T220S K225D /A256D M157F/G138K I35V/E240T

H131C/V221F L152F/L246I K225D/A256E M157F/L238F I35V/N148H

H131C/V221I L152F/A272P K225D/R224L M157F/L238T I35V/F94L

H131C/G245S L152F/ S353E K225D /A134M M157F/I35L I35V/F94Y

H131C/Q92C L152F/ S353K K225D/V359E M157F/I35V I35V/V150L

H131C/Q92S L152F/A256D K225D /V359K M157F/C208A I35V/F68P

H131C/F230A L152F/A256E K225D/ S333A M157F/C208S I35V/N148R

H131C/F230N L152F/R224L K225D / S333E M157F/E240A I35V/K361R

H131C/ S87P L152F/A134M K225D/T352D M157F/E240T I35V/Q280E

H131C/ S87Q L152F/V359E K225D /T352E M157F/N148H I35V/Q280R

H131C/L98H L152F/V359K K225D/M157F M157F/F94L I35V/K225E

H131C/ S70K L152F/ S333A K225D/M157S M157F/F94Y I35V/K225G

H131C/F351A L152F/ S333E K225D/D14G M157F/V150L I35V/L238A

H131C/F351V L152F/T352D K225D /D296A M157F/F68P I35V/L238S

H131C/M157Y L152F/T352E K225D/D296L M157F/N148R I35V/C269A

H131C/C44F L152F/M157F K225D/T314A M157F/K361R I35V/C269I

H131C/C44Y L152F/M157S K225D /T314E M157F/Q280E I35V/D296P

H131C/I3L L152F/D14G K225D/F267Y M157F/Q280R I35V/F140Y

H131C/I3M L152F/D296A K225D /E71N M157F/K225E I35V/I24L

A189G/Q193K L152F/D296L K225D/E252Q M157F/K225G I35V/I24V

A189G/Q193R L152F/T314A K225D/I367V M157F/L238A I35V/D170S

A189G/L242I L152F/T314E K225D/A31M M157F/L238S I35V/V229M

A189G/Q108H L152F/F267Y K225D /A31 S M157F/C269A I35V/E360A

A189G/F68V L152F/E71N K225D /F93A M157F/C269I I35V/ S322V

A189G/G100S L152F/E252Q K225D/L323C M157F/D296P I35V/F347I

A189G/G100T L152F/I367V K225D/L323V M157F/F140Y I35V/V221F

A189G/L323I L152F/A31M K225D /T83G M157F/I24L I35V/V221I

A189G/L323M L152F/A31 S K225D /T83N M157F/I24V I35V/G245S

A189G/Q277D L152F/F93A K225D/Q92R M157F/D170S I35V/Q92C

A189G/Q277E L152F/L323C K225D/F267I M157F/V229M I35V/Q92S

A189G/C269N L152F/L323V K225D/F267Q M157F/E360A I35V/F230A

A189G/C269T L152F/T83G K225D /E4K M157F/ S322V I35V/F230N

A189G/A326F L152F/T83N K225D /E90D M157F/F347I I35V/ S87P

A189G/A326I L152F/Q92R K225D/T312K M157F/V221F I35V/ S87Q

A189G/L152F L152F/F267I K225D/T312N M157F/V221I I35V/L98H

A189G/C282N L152F/F267Q K225D/L241V M157F/G245S I35V/ S70K

A189G/ S329P L152F/E4K K225D/V255I M157F/Q92C I35V/F351A

A189G/I45D L152F/E90D K225D/F344G M157F/Q92S I35V/F351V Positions Positions Positions Positions Positions

A189G/I45L L152F/T312K K225D/I76L M157F/F230A I35V/M157Y

A189G/E258A L152F/T312N K225D/I76M M157F/F230N I35V/C44F

A189G/A272E L152F/L241V K225D/G138K M157F/S87P I35V/C44Y

A189G/T312A L152F/V255I K225D/L238F M157F/S87Q I35V/I3L

A189G/T312R L152F/F344G K225D/L238T M157F/L98H I35V/I3M

A189G/M327Q L152F/I76L K225D/I35L M157F/S70K C208A/C208S

A189G/M327T L152F/I76M K225D/I35V M157F/F351A C208A/E240A

A189G/N174Y L152F/G138K K225D/C208A M157F/F351V C208A/E240T

A189G/L340I L152F/L238F K225D/C208S M157F/M157Y C208A/N148H

A189G/L340M L152F/L238T K225D/E240A M157F/C44F C208A/F94L

A189G/A189H L152F/I35L K225D/E240T M157F/C44Y C208A/F94Y

A189G/A189Y L152F/I35V K225D/N148H M157F/I3L C208A/V150L

A189G/N194R L152F/C208A K225D/F94L M157F/I3M C208A/F68P

A189G/N194S L152F/C208S K225D/F94Y M157S/D14G C208A/N148R

A189G/L169V L152F/E240A K225D/V150L M157S/D296A C208A/K361R

A189G/K225D L152F/E240T K225D/F68P M157S/D296L C208A/Q280E

A189G/K225S L152F/N148H K225D/N148R M157S/T314A C208A/Q280R

A189G/A63I L152F/F94L K225D/K361R M157S/T314E C208A/K225E

A189G/A63P L152F/F94Y K225D/Q280E M157S/F267Y C208A/K225G

A189G/I180L L152F/V150L K225D/Q280R M157S/E71N C208A/L238A

A189G/I180V L152F/F68P K225D/K225E M157S/E252Q C208A/L238S

A189G/H151D L152F/N148R K225D/K225G M157S/I367V C208A/C269A

A189G/T220I L152F/K361R K225D/L238A M157S/A31M C208A/C269I

A189G/T220S L152F/Q280E K225D/L238S M157S/A31S C208A/D296P

A189G/L246I L152F/Q280R K225D/C269A M157S/F93A C208A/F140Y

A189G/A272P L152F/K225E K225D/C269I M157S/L323C C208A/I24L

A189G/S353E L152F/K225G K225D/D296P M157S/L323V C208A/I24V

A189G/S353K L152F/L238A K225D/F140Y M157S/T83G C208A/D170S

A189G/A256D L152F/L238S K225D/I24L M157S/T83N C208A/V229M

A189G/A256E L152F/C269A K225D/I24V M157S/Q92R C208A/E360A

A189G/R224L L152F/C269I K225D/D170S M157S/F267I C208A/S322V

A189G/A134M L152F/D296P K225D/V229M M157S/F267Q C208A/F347I

A189G/V359E L152F/F140Y K225D/E360A M157S/E4K C208A/V221F

A189G/V359K L152F/I24L K225D/S322V M157S/E90D C208A/V221I

A189G/S333A L152F/I24V K225D/F347I M157S/T312K C208A/G245S

A189G/S333E L152F/D170S K225D/V221F M157S/T312N C208A/Q92C

A189G/T352D L152F/V229M K225D/V221I M157S/L241V C208A/Q92S

A189G/T352E L152F/E360A K225D/G245S M157S/V255I C208A/F230A

A189G/M157F L152F/S322V K225D/Q92C M157S/F344G C208A/F230N

A189G/M157S L152F/F347I K225D/Q92S M157S/I76L C208A/S87P

A189G/D14G L152F/V221F K225D/F230A M157S/I76M C208A/S87Q

A189G/D296A L152F/V221I K225D/F230N M157S/G138K C208A/L98H Positions Positions Positions Positions Positions

A189G/D296L L152F/G245S K225D/S87P M157S/L238F C208A/S70K

A189G/T314A L152F/Q92C K225D/S87Q M157S/L238T C208A/F351A

A189G/T314E L152F/Q92S K225D/L98H M157S/I35L C208A/F351V

A189G/F267Y L152F/F230A K225D/S70K M157S/I35V C208A/M157Y

A189G/E71N L152F/F230N K225D/F351A M157S/C208A C208A/C44F

A189G/E252Q L152F/S87P K225D/F351V M157S/C208S C208A/C44Y

A189G/I367V L152F/S87Q K225D/M157Y M157S/E240A C208A/I3L

A189G/A31M L152F/L98H K225D/C44F M157S/E240T C208A/I3M

A189G/A31S L152F/S70K K225D/C44Y M157S/N148H C208S/E240A

A189G/F93A L152F/F351A K225D/I3L M157S/F94L C208S/E240T

A189G/L323C L152F/F351V K225D/I3M M157S/F94Y C208S/N148H

A189G/L323V L152F/M157Y K225S/A63I M157S/V150L C208S/F94L

A189G/T83G L152F/C44F K225S/A63P M157S/F68P C208S/F94Y

A189G/T83N L152F/C44Y K225S/I180L M157S/N148R C208S/V150L

A189G/Q92R L152F/I3L K225S/I180V M157S/K361R C208S/F68P

A189G/F267I L152F/I3M K225S/H151D M157S/Q280E C208S/N148R

A189G/F267Q C282N/S329P K225S/T220I M157S/Q280R C208S/K361R

A189G/E4K C282N/I45D K225S/T220S M157S/K225E C208S/Q280E

A189G/E90D C282N/I45L K225S/L246I M157S/K225G C208S/Q280R

A189G/T312K C282N/E258A K225S/A272P M157S/L238A C208S/K225E

A189G/T312N C282N/A272E K225S/S353E M157S/L238S C208S/K225G

A189G/L241V C282N/T312A K225S/S353K M157S/C269A C208S/L238A

A189G/V255I C282N/T312R K225S/A256D M157S/C269I C208S/L238S

A189G/F344G C282N/M327Q K225S/A256E M157S/D296P C208S/C269A

A189G/I76L C282N/M327T K225S/R224L M157S/F140Y C208S/C269I

A189G/I76M C282N/N174Y K225S/A134M M157S/I24L C208S/D296P

A189G/G138K C282N/L340I K225S/V359E M157S/I24V C208S/F140Y

A189G/L238F C282N/L340M K225S/V359K M157S/D170S C208S/I24L

A189G/L238T C282N/A189H K225S/S333A M157S/V229M C208S/I24V

A189G/I35L C282N/A189Y K225S/S333E M157S/E360A C208S/D170S

A189G/I35V C282N/N194R K225S/T352D M157S/S322V C208S/V229M

A189G/C208A C282N/N194S K225S/T352E M157S/F347I C208S/E360A

A189G/C208S C282N/L169V K225S/M157F M157S/V221F C208S/S322V

A189G/E240A C282N/K225D K225S/M157S M157S/V221I C208S/F347I

A189G/E240T C282N/K225S K225S/D14G M157S/G245S C208S/V221F

A189G/N148H C282N/A63I K225S/D296A M157S/Q92C C208S/V221I

A189G/F94L C282N/A63P K225S/D296L M157S/Q92S C208S/G245S

A189G/F94Y C282N/I180L K225S/T314A M157S/F230A C208S/Q92C

A189G/V150L C282N/I180V K225S/T314E M157S/F230N C208S/Q92S

A189G/F68P C282N/H151D K225S/F267Y M157S/S87P C208S/F230A

A189G/N148R C282N/T220I K225S/E71N M157S/S87Q C208S/F230N

A189G/K361R C282N/T220S K225S/E252Q M157S/L98H C208S/S87P Positions Positions Positions Positions Positions

A189G/Q280E C282N/L246I K225S/I367V M157S/S70K C208S/S87Q

A189G/Q280R C282N/A272P K225S/A31M M157S/F351A C208S/L98H

A189G/K225E C282N/S353E K225S/A31S M157S/F351V C208S/S70K

A189G/K225G C282N/S353K K225S/F93A M157S/M157Y C208S/F351A

A189G/L238A C282N/A256D K225S/L323C M157S/C44F C208S/F351V

A189G/L238S C282N/A256E K225S/L323V M157S/C44Y C208S/M157Y

A189G/C269A C282N/R224L K225S/T83G M157S/I3L C208S/C44F

A189G/C269I C282N/A134M K225S/T83N M157S/I3M C208S/C44Y

A189G/D296P C282N/V359E K225S/Q92R D14G/D296A C208S/I3L

A189G/F140Y C282N/V359K K225S/F267I D14G/D296L C208S/I3M

A189G/I24L C282N/S333A K225S/F267Q D14G/T314A E240A/E240T

A189G/I24V C282N/S333E K225S/E4K D14G/T314E E240A/N148H

A189G/D170S C282N/T352D K225S/E90D D14G/F267Y E240A/F94L

A189G/V229M C282N/T352E K225S/T312K D14G/E71N E240A/F94Y

A189G/E360A C282N/M157F K225S/T312N D14G/E252Q E240A/V150L

A189G/S322V C282N/M157S K225S/L241V D14G/I367V E240A/F68P

A189G/F347I C282N/D14G K225S/V255I D14G/A31M E240A/N148R

A189G/V221F C282N/D296A K225S/F344G D14G/A31S E240A/K361R

A189G/V221I C282N/D296L K225S/I76L D14G/F93A E240A/Q280E

A189G/G245S C282N/T314A K225S/I76M D14G/L323C E240A/Q280R

A189G/Q92C C282N/T314E K225S/G138K D14G/L323V E240A/K225E

A189G/Q92S C282N/F267Y K225S/L238F D14G/T83G E240A/K225G

A189G/F230A C282N/E71N K225S/L238T D14G/T83N E240A/L238A

A189G/F230N C282N/E252Q K225S/I35L D14G/Q92R E240A/L238S

A189G/S87P C282N/I367V K225S/I35V D14G/F267I E240A/C269A

A189G/S87Q C282N/A31M K225S/C208A D14G/F267Q E240A/C269I

A189G/L98H C282N/A31S K225S/C208S D14G/E4K E240A/D296P

A189G/S70K C282N/F93A K225S/E240A D14G/E90D E240A/F140Y

A189G/F351A C282N/L323C K225S/E240T D14G/T312K E240A/I24L

A189G/F351V C282N/L323V K225S/N148H D14G/T312N E240A/I24V

A189G/M157Y C282N/T83G K225S/F94L D14G/L241V E240A/D170S

A189G/C44F C282N/T83N K225S/F94Y D14G/V255I E240A/V229M

A189G/C44Y C282N/Q92R K225S/V150L D14G/F344G E240A/E360A

A189G/I3L C282N/F267I K225S/F68P D14G/I76L E240A/S322V

A189G/I3M C282N/F267Q K225S/N148R D14G/I76M E240A/F347I

Q193K/Q193R C282N/E4K K225S/K361R D14G/G138K E240A/V221F

Q193K/L242I C282N/E90D K225S/Q280E D14G/L238F E240A/V221I

Q193K/Q108H C282N/T312K K225S/Q280R D14G/L238T E240A/G245S

Q193K/F68V C282N/T312N K225S/K225E D14G/I35L E240A/Q92C

Q193K/G100S C282N/L241V K225S/K225G D14G/I35V E240A/Q92S

Q193K/G100T C282N/V255I K225S/L238A D14G/C208A E240A/F230A

Q193K/L323I C282N/F344G K225S/L238S D14G/C208S E240A/F230N Positions Positions Positions Positions Positions

Q193K/L323M C282N/I76L K225S/C269A D14G/E240A E240A/S87P

Q193K/Q277D C282N/I76M K225S/C269I D14G/E240T E240A/S87Q

Q193K/Q277E C282N/G138K K225S/D296P D14G/N148H E240A/L98H

Q193K/C269N C282N/L238F K225S/F140Y D14G/F94L E240A/S70K

Q193K/C269T C282N/L238T K225S/I24L D14G/F94Y E240A/F351A

Q193K/A326F C282N/I35L K225S/I24V D14G/V150L E240A/F351V

Q193K/A326I C282N/I35V K225S/D170S D14G/F68P E240A/M157Y

Q193K/L152F C282N/C208A K225S/V229M D14G/N148R E240A/C44F

Q193K/C282N C282N/C208S K225S/E360A D14G/K361R E240A/C44Y

Q193K/S329P C282N/E240A K225S/S322V D14G/Q280E E240A/I3L

Q193K/I45D C282N/E240T K225S/F347I D14G/Q280R E240A/I3M

Q193K/I45L C282N/N148H K225S/V221F D14G/K225E E240T/N148H

Q193K/E258A C282N/F94L K225S/V221I D14G/K225G E240T/F94L

Q193K/A272E C282N/F94Y K225S/G245S D14G/L238A E240T/F94Y

Q193K/T312A C282N/V150L K225S/Q92C D14G/L238S E240T/V150L

Q193K/T312R C282N/F68P K225S/Q92S D14G/C269A E240T/F68P

Q193K/M327Q C282N/N148R K225S/F230A D14G/C269I E240T/N148R

Q193K/M327T C282N/K361R K225S/F230N D14G/D296P E240T/K361R

Q193K/N174Y C282N/Q280E K225S/S87P D14G/F140Y E240T/Q280E

Q193K/L340I C282N/Q280R K225S/S87Q D14G/I24L E240T/Q280R

Q193K/L340M C282N/K225E K225S/L98H D14G/I24V E240T/K225E

Q193K/A189H C282N/K225G K225S/S70K D14G/D170S E240T/K225G

Q193K/A189Y C282N/L238A K225S/F351A D14G/V229M E240T/L238A

Q193K/N194R C282N/L238S K225S/F351V D14G/E360A E240T/L238S

Q193K/N194S C282N/C269A K225S/M157Y D14G/S322V E240T/C269A

Q193K/L169V C282N/C269I K225S/C44F D14G/F347I E240T/C269I

Q193K/K225D C282N/D296P K225S/C44Y D14G/V221F E240T/D296P

Q193K/K225S C282N/F140Y K225S/I3L D14G/V221I E240T/F140Y

Q193K/A63I C282N/I24L K225S/I3M D14G/G245S E240T/I24L

Q193K/A63P C282N/I24V A63I/A63P D14G/Q92C E240T/I24V

Q193K/I180L C282N/D170S A63I/I180L D14G/Q92S E240T/D170S

Q193K/I180V C282N/V229M A63I/I180V D14G/F230A E240T/V229M

Q193K/H151D C282N/E360A A63I/H151D D14G/F230N E240T/E360A

Q193K/T220I C282N/S322V A63I/T220I D14G/S87P E240T/S322V

Q193K/T220S C282N/F347I A63I/T220S D14G/S87Q E240T/F347I

Q193K/L246I C282N/V221F A63I/L246I D14G/L98H E240T/V221F

Q193K/A272P C282N/V221I A63I/A272P D14G/S70K E240T/V221I

Q193K/S353E C282N/G245S A63I/S353E D14G/F351A E240T/G245S

Q193K/S353K C282N/Q92C A63I/S353K D14G/F351V E240T/Q92C

Q193K/A256D C282N/Q92S A63I/A256D D14G/M157Y E240T/Q92S

Q193K/A256E C282N/F230A A63I/A256E D14G/C44F E240T/F230A

Q193K/R224L C282N/F230N A63I/R224L D14G/C44Y E240T/F230N Positions Positions Positions Positions Positions

Q193K/A134M C282N/ S87P A63I/A134M D14G/I3L E240T/ S87P

Q193K/V359E C282N/ S87Q A63I/V359E D14G/I3M E240T/ S87Q

Q193K/V359K C282N/L98H A63I/V359K D296A/D296L E240T/L98H

Q193K/ S333A C282N/ S70K A63I/ S333A D296A/T314A E240T/ S70K

Q193K/ S333E C282N/F351A A63I/ S333E D296A/T314E E240T/F351A

Q193K/T352D C282N/F351V A63I/T352D D296A/F267Y E240T/F351V

Q193K/T352E C282N/M157Y A63I/T352E D296A/E71N E240T/M157Y

Q193K/M157F C282N/C44F A63I/M157F D296A/E252Q E240T/C44F

Q193K/M157S C282N/C44Y A63I/M157S D296A/I367V E240T/C44Y

Q193K/D14G C282N/I3L A63I/D14G D296A/A31M E240T/I3L

Q193K/D296A C282N/I3M A63I/D296A D296A/A31 S E240T/I3M

Q193K/D296L S329P/I45D A63I/D296L D296A/F93A N148H/F94L

Q193K/T314A S329P/I45L A63I/T314A D296A/L323C N148H/F94Y

Q193K/T314E S329P/E258A A63I/T314E D296A/L323V N148H/V150L

Q193K/F267Y S329P/A272E A63I/F267Y D296A/T83G N148H/F68P

Q193K/E71N S329P/T312A A63I/E71N D296A/T83N N148H/N148R

Q193K/E252Q S329P/T312R A63I/E252Q D296A/Q92R N148H/K361R

Q193K/I367V S329P/M327Q A63I/I367V D296A/F267I N148H/Q280E

Q193K/A31M S329P/M327T A63I/A31M D296A/F267Q N148H/Q280R

Q193K/A31 S S329P/N174Y A63I/A31 S D296A/E4K N148H/K225E

Q193K/F93A S329P/L340I A63I/F93A D296A/E90D N148H/K225G

Q193K/L323C S329P/L340M A63I/L323C D296A/T312K N148H/L238A

Q193K/L323V S329P/A189H A63I/L323V D296A/T312N N148H/L238S

Q193K/T83G S329P/A189Y A63I/T83G D296A/L241V N148H/C269A

Q193K/T83N S329P/N194R A63I/T83N D296A/V255I N148H/C269I

Q193K/Q92R S329P/N194S A63I/Q92R D296A/F344G N148H/D296P

Q193K/F267I S329P/L169V A63I/F267I D296A/I76L N148H/F140Y

Q193K/F267Q S329P/K225D A63I/F267Q D296A/I76M N148H/I24L

Q193K/E4K S329P/K225S A63I/E4K D296A/G138K N148H/I24V

Q193K/E90D S329P/A63I A63I/E90D D296A/L238F N148H/D170S

Q193K/T312K S329P/A63P A63I/T312K D296A/L238T N148H/V229M

Q193K/T312N S329P/I180L A63I/T312N D296A/I35L N148H/E360A

Q193K/L241V S329P/I180V A63I/L241V D296A/I35V N148H/ S322V

Q193K/V255I S329P/H151D A63I/V255I D296A/C208A N148H/F347I

Q193K/F344G S329P/T220I A63I/F344G D296A/C208S N148H/V221F

Q193K/I76L S329P/T220S A63I/I76L D296A/E240A N148H/V221I

Q193K/I76M S329P/L246I A63I/I76M D296A/E240T N148H/G245S

Q193K/G138K S329P/A272P A63I/G138K D296A/N148H N148H/Q92C

Q193K/L238F S329P/ S353E A63I/L238F D296A/F94L N148H/Q92S

Q193K/L238T S329P/ S353K A63I/L238T D296A/F94Y N148H/F230A

Q193K/I35L S329P/A256D A63I/I35L D296A/V150L N148H/F230N

Q193K/I35V S329P/A256E A63I/I35V D296A/F68P N148H/ S87P Positions Positions Positions Positions Positions

Q193K/C208A S329P/R224L A63I/C208A D296A/N148R N148H/ S87Q

Q193K/C208S S329P/A134M A63I/C208S D296A/K361R N148H/L98H

Q193K/E240A S329P/V359E A63I/E240A D296A/Q280E N148H/ S70K

Q193K/E240T S329P/V359K A63I/E240T D296A/Q280R N148H/F351A

Q193K/N148H S329P/ S333A A63I/N148H D296A/K225E N148H/F351V

Q193K/F94L S329P/ S333E A63I/F94L D296A/K225G N148H/M157Y

Q193K/F94Y S329P/T352D A63I/F94Y D296A/L238A N148H/C44F

Q193K/V150L S329P/T352E A63I/V150L D296A/L238S N148H/C44Y

Q193K/F68P S329P/M157F A63I/F68P D296A/C269A N148H/I3L

Q193K/N148R S329P/M157S A63I/N148R D296A/C269I N148H/I3M

Q193K/K361R S329P/D14G A63I/K361R D296A/D296P F94L/F94Y

Q193K/Q280E S329P/D296A A63I/Q280E D296A/F140Y F94L/V150L

Q193K/Q280R S329P/D296L A63I/Q280R D296A/I24L F94L/F68P

Q193K/K225E S329P/T314A A63I/K225E D296A/I24V F94L/N148R

Q193K/K225G S329P/T314E A63I/K225G D296A/D170S F94L/K361R

Q193K/L238A S329P/F267Y A63I/L238A D296A/V229M F94L/Q280E

Q193K/L238S S329P/E71N A63I/L238S D296A/E360A F94L/Q280R

Q193K/C269A S329P/E252Q A63I/C269A D296A/ S322V F94L/K225E

Q193K/C269I S329P/I367V A63I/C269I D296A/F347I F94L/K225G

Q193K/D296P S329P/A31M A63I/D296P D296A/V221F F94L/L238A

Q193K/F140Y S329P/A31 S A63I/F140Y D296A/V221I F94L/L238S

Q193K/I24L S329P/F93A A63I/I24L D296A/G245S F94L/C269A

Q193K/I24V S329P/L323C A63I/I24V D296A/Q92C F94L/C269I

Q193K/D170S S329P/L323V A63I/D170S D296A/Q92S F94L/D296P

Q193K/V229M S329P/T83G A63I/V229M D296A/F230A F94L/F140Y

Q193K/E360A S329P/T83N A63I/E360A D296A/F230N F94L/I24L

Q193K/ S322V S329P/Q92R A63I/ S322V D296A/ S87P F94L/I24V

Q193K/F347I S329P/F267I A63I/F347I D296A/ S87Q F94L/D170S

Q193K/V221F S329P/F267Q A63I/V221F D296A/L98H F94L/V229M

Q193K/V221I S329P/E4K A63I/V221I D296A/ S70K F94L/E360A

Q193K/G245S S329P/E90D A63I/G245S D296A/F351A F94L/ S322V

Q193K/Q92C S329P/T312K A63I/Q92C D296A/F351V F94L/F347I

Q193K/Q92S S329P/T312N A63I/Q92S D296A/M157Y F94L/V221F

Q193K/F230A S329P/L241V A63I/F230A D296A/C44F F94L/V221I

Q193K/F230N S329P/V255I A63I/F230N D296A/C44Y F94L/G245S

Q193K/ S87P S329P/F344G A63I/ S87P D296A/I3L F94L/Q92C

Q193K/ S87Q S329P/I76L A63I/ S87Q D296A/I3M F94L/Q92S

Q193K/L98H S329P/I76M A63I/L98H D296L/T314A F94L/F230A

Q193K/ S70K S329P/G138K A63I/ S70K D296L/T314E F94L/F230N

Q193K/F351A S329P/L238F A63I/F351A D296L/F267Y F94L/ S87P

Q193K/F351V S329P/L238T A63I/F351V D296L/E71N F94L/ S87Q

Q193K/M157Y S329P/I35L A63I/M157Y D296L/E252Q F94L/L98H Positions Positions Positions Positions Positions

Q193K/C44F S329P/I35V A63I/C44F D296L/I367V F94L/ S70K

Q193K/C44Y S329P/C208A A63I/C44Y D296L/A31M F94L/F351A

Q193K/I3L S329P/C208S A63I/I3L D296L/A31 S F94L/F351V

Q193K/I3M S329P/E240A A63I/I3M D296L/F93A F94L/M157Y

Q193R/L242I S329P/E240T A63P/I180L D296L/L323C F94L/C44F

Q193R/Q108H S329P/N148H A63P/I180V D296L/L323V F94L/C44Y

Q193R/F68V S329P/F94L A63P/H151D D296L/T83G F94L/I3L

Q193R/G100S S329P/F94Y A63P/T220I D296L/T83N F94L/I3M

Q193R/G100T S329P/V150L A63P/T220S D296L/Q92R F94Y/V150L

Q193R/L323I S329P/F68P A63P/L246I D296L/F267I F94Y/F68P

Q193R/L323M S329P/N148R A63P/A272P D296L/F267Q F94Y/N148R

Q193R/Q277D S329P/K361R A63P/ S353E D296L/E4K F94Y/K361R

Q193R/Q277E S329P/Q280E A63P/ S353K D296L/E90D F94Y/Q280E

Q193R/C269N S329P/Q280R A63P/A256D D296L/T312K F94Y/Q280R

Q193R/C269T S329P/K225E A63P/A256E D296L/T312N F94Y/K225E

Q193R/A326F S329P/K225G A63P/R224L D296L/L241V F94Y/K225G

Q193R/A326I S329P/L238A A63P/A134M D296L/V255I F94Y/L238A

Q193R/L152F S329P/L238S A63P/V359E D296L/F344G F94Y/L238S

Q193R/C282N S329P/C269A A63P/V359K D296L/I76L F94Y/C269A

Q193R/ S329P S329P/C269I A63P/ S333A D296L/I76M F94Y/C269I

Q193R/I45D S329P/D296P A63P/ S333E D296L/G138K F94Y/D296P

Q193R/I45L S329P/F140Y A63P/T352D D296L/L238F F94Y/F140Y

Q193R/E258A S329P/I24L A63P/T352E D296L/L238T F94Y/I24L

Q193R/A272E S329P/I24V A63P/M157F D296L/I35L F94Y/I24V

Q193R/T312A S329P/D170S A63P/M157S D296L/I35V F94Y/D170S

Q193R/T312R S329P/V229M A63P/D14G D296L/C208A F94Y/V229M

Q193R/M327Q S329P/E360A A63P/D296A D296L/C208S F94Y/E360A

Q193R/M327T S329P/ S322V A63P/D296L D296L/E240A F94Y/ S322V

Q193R/N174Y S329P/F347I A63P/T314A D296L/E240T F94Y/F347I

Q193R/L340I S329P/V221F A63P/T314E D296L/N148H F94Y/V221F

Q193R/L340M S329P/V221I A63P/F267Y D296L/F94L F94Y/V221I

Q193R/A189H S329P/G245S A63P/E71N D296L/F94Y F94Y/G245S

Q193R/A189Y S329P/Q92C A63P/E252Q D296L/V150L F94Y/Q92C

Q193R/N194R S329P/Q92S A63P/I367V D296L/F68P F94Y/Q92S

Q193R/N194S S329P/F230A A63P/A31M D296L/N148R F94Y/F230A

Q193R/L169V S329P/F230N A63P/A31 S D296L/K361R F94Y/F230N

Q193R/K225D S329P/ S87P A63P/F93A D296L/Q280E F94Y/ S87P

Q193R/K225S S329P/ S87Q A63P/L323C D296L/Q280R F94Y/ S87Q

Q193R/A63I S329P/L98H A63P/L323V D296L/K225E F94Y/L98H

Q193R/A63P S329P/ S70K A63P/T83G D296L/K225G F94Y/ S70K

Q193R/I180L S329P/F351A A63P/T83N D296L/L238A F94Y/F351A

Q193R/I180V S329P/F351V A63P/Q92R D296L/L238S F94Y/F351V Positions Positions Positions Positions Positions

Q193R/H151D S329P/M157Y A63P/F267I D296L/C269A F94Y/M157Y

Q193R/T220I S329P/C44F A63P/F267Q D296L/C269I F94Y/C44F

Q193R/T220S S329P/C44Y A63P/E4K D296L/D296P F94Y/C44Y

Q193R/L246I S329P/I3L A63P/E90D D296L/F140Y F94Y/I3L

Q193R/A272P S329P/I3M A63P/T312K D296L/I24L F94Y/I3M

Q193R/ S353E I45D /I45L A63P/T312N D296L/I24V V150L/F68P

Q193R/ S353K I45D /E258A A63P/L241V D296L/D170S V150L/N148R

Q193R/A256D I45D /A272E A63P/V255I D296L/V229M V150L/K361R

Q193R/A256E I45D /T312A A63P/F344G D296L/E360A V150L/Q280E

Q193R/R224L I45D /T312R A63P/I76L D296L/ S322V V150L/Q280R

Q193R/A134M I45D/M327Q A63P/I76M D296L/F347I V150L/K225E

Q193R/V359E I45D /M327T A63P/G138K D296L/V221F V150L/K225G

Q193R/V359K I45D/N174Y A63P/L238F D296L/V221I V150L/L238A

Q193R/ S333A I45D/L340I A63P/L238T D296L/G245S V150L/L238S

Q193R/ S333E I45D /L340M A63P/I35L D296L/Q92C V150L/C269A

Q193R/T352D I45D/A189H A63P/I35V D296L/Q92S V150L/C269I

Q193R/T352E I45D/A189Y A63P/C208A D296L/F230A V150L/D296P

Q193R/M157F I45D/N194R A63P/C208S D296L/F230N V150L/F140Y

Q193R/M157S I45D /N194S A63P/E240A D296L/ S87P V150L/I24L

Q193R/D14G I45D /L169V A63P/E240T D296L/ S87Q V150L/I24V

Q193R/D296A I45D/K225D A63P/N148H D296L/L98H V150L/D170S

Q193R/D296L I45D /K225S A63P/F94L D296L/ S70K V150L/V229M

Q193R/T314A I45D/A63I A63P/F94Y D296L/F351A V150L/E360A

Q193R/T314E I45D/A63P A63P/V150L D296L/F351V V150L/ S322V

Q193R/F267Y I45D/I180L A63P/F68P D296L/M157Y V150L/F347I

Q193R/E71N I45D /I180V A63P/N148R D296L/C44F V150L/V221F

Q193R/E252Q I45D/H151D A63P/K361R D296L/C44Y V150L/V221I

Q193R/I367V I45D/T220I A63P/Q280E D296L/I3L V150L/G245S

Q193R/A31M I45D/T220S A63P/Q280R D296L/I3M V150L/Q92C

Q193R/A31 S I45D/L246I A63P/K225E T314A/T314E V150L/Q92S

Q193R/F93A I45D /A272P A63P/K225G T314A/F267Y V150L/F230A

Q193R/L323C I45D/ S353E A63P/L238A T314A/E71N V150L/F230N

Q193R/L323V I45D / S353K A63P/L238S T314A/E252Q V150L/ S87P

Q193R/T83G I45D/A256D A63P/C269A T314A/I367V V150L/ S87Q

Q193R/T83N I45D /A256E A63P/C269I T314A/A31M V150L/L98H

Q193R/Q92R I45D /R224L A63P/D296P T314A/A31 S V150L/ S70K

Q193R/F267I I45D/A134M A63P/F140Y T314A/F93A V150L/F351A

Q193R/F267Q I45D /V359E A63P/I24L T314A/L323C V150L/F351V

Q193R/E4K I45D/V359K A63P/I24V T314A/L323V V150L/M157Y

Q193R/E90D I45D / S333A A63P/D170S T314A/T83G V150L/C44F

Q193R/T312K I45D/ S333E A63P/V229M T314A/T83N V150L/C44Y

Q193R/T312N I45D /T352D A63P/E360A T314A/Q92R V150L/I3L Positions Positions Positions Positions Positions

Q193R/L241V I45D/T352E A63P/ S322V T314A/F267I V150L/I3M

Q193R/V255I I45D /M157F A63P/F347I T314A/F267Q F68P/N148R

Q193R/F344G I45D /M157S A63P/V221F T314A/E4K F68P/K361R

Q193R/I76L I45D/D14G A63P/V221I T314A/E90D F68P/Q280E

Q193R/I76M I45D/D296A A63P/G245S T314A/T312K F68P/Q280R

Q193R/G138K I45D /D296L A63P/Q92C T314A/T312N F68P/K225E

Q193R/L238F I45D /T314A A63P/Q92S T314A/L241V F68P/K225G

Q193R/L238T I45D/T314E A63P/F230A T314A/V255I F68P/L238A

Q193R/I35L I45D/F267Y A63P/F230N T314A/F344G F68P/L238S

Q193R/I35V I45D/E71N A63P/ S87P T314A/I76L F68P/C269A

Q193R/C208A I45D /E252Q A63P/ S87Q T314A/I76M F68P/C269I

Q193R/C208S I45D /I367V A63P/L98H T314A/G138K F68P/D296P

Q193R/E240A I45D /A31M A63P/ S70K T314A/L238F F68P/F140Y

Q193R/E240T I45D/A31 S A63P/F351A T314A/L238T F68P/I24L

Q193R/N148H I45D/F93A A63P/F351V T314A/I35L F68P/I24V

Q193R/F94L I45D /L323C A63P/M157Y T314A/I35V F68P/D170S

Q193R/F94Y I45D /L323V A63P/C44F T314A/C208A F68P/V229M

Q193R/V150L I45D/T83G A63P/C44Y T314A/C208S F68P/E360A

Q193R/F68P I45D/T83N A63P/I3L T314A/E240A F68P/ S322V

Q193R/N148R I45D /Q92R A63P/I3M T314A/E240T F68P/F347I

Q193R/K361R I45D /F267I I180L/I180V T314A/N148H F68P/V221F

Q193R/Q280E I45D /F267Q I180L/H151D T314A/F94L F68P/V221I

Q193R/Q280R I45D/E4K I180L/T220I T314A/F94Y F68P/G245S

Q193R/K225E I45D/E90D I180L/T220S T314A/V150L F68P/Q92C

Q193R/K225G I45D /T312K I180L/L246I T314A/F68P F68P/Q92S

Q193R/L238A I45D /T312N I180L/A272P T314A/N148R F68P/F230A

Q193R/L238S I45D /L241V I180L/ S353E T314A/K361R F68P/F230N

Q193R/C269A I45D /V255I I180L/ S353K T314A/Q280E F68P/ S87P

Q193R/C269I I45D /F344G I180L/A256D T314A/Q280R F68P/ S87Q

Q193R/D296P I45D /I76L I180L/A256E T314A/K225E F68P/L98H

Q193R/F140Y I45D /I76M I180L/R224L T314A/K225G F68P/ S70K

Q193R/I24L I45D/G138K I180L/A134M T314A/L238A F68P/F351A

Q193R/I24V I45D/L238F I180L/V359E T314A/L238S F68P/F351V

Q193R/D170S I45D/L238T I180L/V359K T314A/C269A F68P/M157Y

Q193R/V229M I45D /I35L I180L/ S333A T314A/C269I F68P/C44F

Q193R/E360A I45D/I35V I180L/ S333E T314A/D296P F68P/C44Y

Q193R/ S322V I45D/C208A I180L/T352D T314A/F140Y F68P/I3L

Q193R/F347I I45D/C208S I180L/T352E T314A/I24L F68P/I3M

Q193R/V221F I45D /E240A I180L/M157F T314A/I24V N148R/K361R

Q193R/V221I I45D/E240T I180L/M157S T314A/D170S N148R/Q280E

Q193R/G245S I45D/N148H I180L/D14G T314A/V229M N148R/Q280R

Q193R/Q92C I45D /F94L I180L/D296A T314A/E360A N148R/K225E Positions Positions Positions Positions Positions

Q193R/Q92S I45D/F94Y I180L/D296L T314A/ S322V N148R/K225G

Q193R/F230A I45D /V150L I180L/T314A T314A/F347I N148R/L238A

Q193R/F230N I45D/F68P I180L/T314E T314A/V221F N148R/L238S

Q193R/ S87P I45D/N148R I180L/F267Y T314A/V221I N148R/C269A

Q193R/ S87Q I45D/K361R I180L/E71N T314A/G245S N148R/C269I

Q193R/L98H I45D /Q280E I180L/E252Q T314A/Q92C N148R/D296P

Q193R/ S70K I45D/Q280R I180L/I367V T314A/Q92S N148R/F140Y

Q193R/F351A I45D /K225E I180L/A31M T314A/F230A N148R/I24L

Q193R/F351V I45D/K225G I180L/A31 S T314A/F230N N148R/I24V

Q193R/M157Y I45D /L238A I180L/F93A T314A/ S87P N148R/D170S

Q193R/C44F I45D/L238S I180L/L323C T314A/ S87Q N148R/V229M

Q193R/C44Y I45D/C269A I180L/L323V T314A/L98H N148R/E360A

Q193R/I3L I45D/C269I I180L/T83G T314A/ S70K N148R/ S322V

Q193R/I3M I45D /D296P I180L/T83N T314A/F351A N148R/F347I

L242I/Q108H I45D /F140Y I180L/Q92R T314A/F351V N148R/V221F

L242I/F68V I45D /I24L I180L/F267I T314A/M157Y N148R/V221I

L242I/G100S I45D/I24V I180L/F267Q T314A/C44F N148R/G245S

L242I/G100T I45D /D170S I180L/E4K T314A/C44Y N148R/Q92C

L242I/L323I I45D/V229M I180L/E90D T314A/I3L N148R/Q92S

L242I/L323M I45D /E360A I180L/T312K T314A/I3M N148R/F230A

L242I/Q277D I45D / S322V I180L/T312N T314E/F267Y N148R/F230N

L242I/Q277E I45D /F347I I180L/L241V T314E/E71N N148R/ S87P

L242I/C269N I45D/V221F I180L/V255I T314E/E252Q N148R/ S87Q

L242I/C269T I45D /V221I I180L/F344G T314E/I367V N148R/L98H

L242I/A326F I45D /G245S I180L/I76L T314E/A31M N148R/ S70K

L242I/A326I I45D /Q92C I180L/I76M T314E/A31 S N148R/F351A

L242I/L152F I45D/Q92S I180L/G138K T314E/F93A N148R/F351V

L242I/C282N I45D/F230A I180L/L238F T314E/L323C N148R/M157Y

L242I/ S329P I45D /F230N I180L/L238T T314E/L323V N148R/C44F

L242I/I45D I45D/ S87P I180L/I35L T314E/T83G N148R/C44Y

L242I/I45L I45D/ S87Q I180L/I35V T314E/T83N N148R/I3L

L242I/E258A I45D/L98H I180L/C208A T314E/Q92R N148R/I3M

L242I/A272E I45D/ S70K I180L/C208S T314E/F267I K361R/Q280E

L242I/T312A I45D /F351A I180L/E240A T314E/F267Q K361R/Q280R

L242I/T312R I45D /F351V I180L/E240T T314E/E4K K361R/K225E

L242I/M327Q I45D/M157Y I180L/N148H T314E/E90D K361R/K225G

L242I/M327T I45D /C44F I180L/F94L T314E/T312K K361R/L238A

L242I/N174Y I45D /C44Y I180L/F94Y T314E/T312N K361R/L238S

L242I/L340I I45D/I3L I180L/V150L T314E/L241V K361R/C269A

L242I/L340M I45D/I3M I180L/F68P T314E/V255I K361R/C269I

L242I/A189H I45L/E258A I180L/N148R T314E/F344G K361R/D296P

L242I/A189Y I45L/A272E I180L/K361R T314E/I76L K361R/F140Y Positions Positions Positions Positions Positions

L242I/N194R I45L/T312A I180L/Q280E T314E/I76M K361R/I24L

L242I/N194S I45L/T312R I180L/Q280R T314E/G138K K361R/I24V

L242I/L169V I45L/M327Q I180L/K225E T314E/L238F K361R/D170S

L242I/K225D I45L/M327T I180L/K225G T314E/L238T K361R/V229M

L242I/K225S I45L/N174Y I180L/L238A T314E/I35L K361R/E360A

L242I/A63I I45L/L340I I180L/L238S T314E/I35V K361R/ S322V

L242I/A63P I45L/L340M I180L/C269A T314E/C208A K361R/F347I

L242I/I180L I45L/A189H I180L/C269I T314E/C208S K361R/V221F

L242I/I180V I45L/A189Y I180L/D296P T314E/E240A K361R/V221I

L242I/H151D I45L/N194R I180L/F140Y T314E/E240T K361R/G245S

L242I/T220I I45L/N194S I180L/I24L T314E/N148H K361R/Q92C

L242I/T220S I45L/L169V I180L/I24V T314E/F94L K361R/Q92S

L242I/L246I I45L/K225D I180L/D170S T314E/F94Y K361R/F230A

L242I/A272P I45L/K225S I180L/V229M T314E/V150L K361R/F230N

L242I/ S353E I45L/A63I I180L/E360A T314E/F68P K361R/ S87P

L242I/ S353K I45L/A63P I180L/ S322V T314E/N148R K361R/ S87Q

L242I/A256D I45L/I180L I180L/F347I T314E/K361R K361R/L98H

L242I/A256E I45L/I180V I180L/V221F T314E/Q280E K361R/ S70K

L242I/R224L I45L/H151D I180L/V221I T314E/Q280R K361R/F351A

L242I/A134M I45L/T220I I180L/G245S T314E/K225E K361R/F351V

L242I/V359E I45L/T220S I180L/Q92C T314E/K225G K361R/M157Y

L242I/V359K I45L/L246I I180L/Q92S T314E/L238A K361R/C44F

L242I/ S333A I45L/A272P I180L/F230A T314E/L238S K361R/C44Y

L242I/ S333E I45L/ S353E I180L/F230N T314E/C269A K361R/I3L

L242I/T352D I45L/ S353K I180L/ S87P T314E/C269I K361R/I3M

L242I/T352E I45L/A256D I180L/ S87Q T314E/D296P Q280E/Q280R

L242I/M157F I45L/A256E I180L/L98H T314E/F140Y Q280E/K225E

L242I/M157S I45L/R224L I180L/ S70K T314E/I24L Q280E/K225G

L242I/D14G I45L/A134M I180L/F351A T314E/I24V Q280E/L238A

L242I/D296A I45L/V359E I180L/F351V T314E/D170S Q280E/L238S

L242I/D296L I45L/V359K I180L/M157Y T314E/V229M Q280E/C269A

L242I/T314A I45L/ S333A I180L/C44F T314E/E360A Q280E/C269I

L242I/T314E I45L/ S333E I180L/C44Y T314E/ S322V Q280E/D296P

L242I/F267Y I45L/T352D I180L/I3L T314E/F347I Q280E/F140Y

L242I/E71N I45L/T352E I180L/I3M T314E/V221F Q280E/I24L

L242I/E252Q I45L/M157F I180V/H151D T314E/V221I Q280E/I24V

L242I/I367V I45L/M157S I180V/T220I T314E/G245S Q280E/D170S

L242I/A31M I45L/D14G I180V/T220S T314E/Q92C Q280E/V229M

L242I/A31 S I45L/D296A I180V/L246I T314E/Q92S Q280E/E360A

L242I/F93A I45L/D296L I180V/A272P T314E/F230A Q280E/ S322V

L242I/L323C I45L/T314A I180V/ S353E T314E/F230N Q280E/F347I

L242I/L323V I45L/T314E I180V/ S353K T314E/ S87P Q280E/V221F Positions Positions Positions Positions Positions

L242I/T83G I45L/F267Y I180V/A256D T314E/ S87Q Q280E/V221I

L242I/T83N I45L/E71N I180V/A256E T314E/L98H Q280E/G245S

L242I/Q92R I45L/E252Q I180V/R224L T314E/ S70K Q280E/Q92C

L242I/F267I I45L/I367V I180V/A134M T314E/F351A Q280E/Q92S

L242I/F267Q I45L/A31M I180V/V359E T314E/F351V Q280E/F230A

L242I/E4K I45L/A31 S I180V/V359K T314E/M157Y Q280E/F230N

L242I/E90D I45L/F93A I180V/ S333A T314E/C44F Q280E/ S87P

L242I/T312K I45L/L323C I180V/ S333E T314E/C44Y Q280E/ S87Q

L242I/T312N I45L/L323V I180V/T352D T314E/I3L Q280E/L98H

L242I/L241V I45L/T83G I180V/T352E T314E/I3M Q280E/ S70K

L242I/V255I I45L/T83N I180V/M157F F267Y/E71N Q280E/F351A

L242I/F344G I45L/Q92R I180V/M157S F267Y/E252Q Q280E/F351V

L242I/I76L I45L/F267I I180V/D14G F267Y/I367V Q280E/M157Y

L242I/I76M I45L/F267Q I180V/D296A F267Y/A31M Q280E/C44F

L242I/G138K I45L/E4K I180V/D296L F267Y/A31 S Q280E/C44Y

L242I/L238F I45L/E90D I180V/T314A F267Y/F93A Q280E/I3L

L242I/L238T I45L/T312K I180V/T314E F267Y/L323C Q280E/I3M

L242I/I35L I45L/T312N I180V/F267Y F267Y/L323V Q280R/K225E

L242I/I35V I45L/L241V I180V/E71N F267Y/T83G Q280R/K225G

L242I/C208A I45L/V255I I180V/E252Q F267Y/T83N Q280R/L238A

L242I/C208S I45L/F344G I180V/I367V F267Y/Q92R Q280R/L238S

L242I/E240A I45L/I76L I180V/A31M F267Y/F267I Q280R/C269A

L242I/E240T I45L/I76M I180V/A31 S F267Y/F267Q Q280R/C269I

L242I/N148H I45L/G138K I180V/F93A F267Y/E4K Q280R/D296P

L242I/F94L I45L/L238F I180V/L323C F267Y/E90D Q280R/F140Y

L242I/F94Y I45L/L238T I180V/L323V F267Y/T312K Q280R/I24L

L242I/V150L I45L/I35L I180V/T83G F267Y/T312N Q280R/I24V

L242I/F68P I45L/I35V I180V/T83N F267Y/L241V Q280R/D170S

L242I/N148R I45L/C208A I180V/Q92R F267Y/V255I Q280R/V229M

L242I/K361R I45L/C208S I180V/F267I F267Y/F344G Q280R/E360A

L242I/Q280E I45L/E240A I180V/F267Q F267Y/I76L Q280R/ S322V

L242I/Q280R I45L/E240T I180V/E4K F267Y/I76M Q280R/F347I

L242I/K225E I45L/N148H I180V/E90D F267Y/G138K Q280R/V221F

L242I/K225G I45L/F94L I180V/T312K F267Y/L238F Q280R/V221I

L242I/L238A I45L/F94Y I180V/T312N F267Y/L238T Q280R/G245S

L242I/L238S I45L/V150L I180V/L241V F267Y/I35L Q280R/Q92C

L242I/C269A I45L/F68P I180V/V255I F267Y/I35V Q280R/Q92S

L242I/C269I I45L/N148R I180V/F344G F267Y/C208A Q280R/F230A

L242I/D296P I45L/K361R I180V/I76L F267Y/C208S Q280R/F230N

L242I/F140Y I45L/Q280E I180V/I76M F267Y/E240A Q280R/ S87P

L242I/I24L I45L/Q280R I180V/G138K F267Y/E240T Q280R/ S87Q

L242I/I24V I45L/K225E I180V/L238F F267Y/N148H Q280R/L98H Positions Positions Positions Positions Positions

L242I/D170S I45L/K225G I180V/L238T F267Y/F94L Q280R/ S70K

L242I/V229M I45L/L238A I180V/I35L F267Y/F94Y Q280R/F351A

L242I/E360A I45L/L238S I180V/I35V F267Y/V150L Q280R/F351V

L242I/ S322V I45L/C269A I180V/C208A F267Y/F68P Q280R/M157Y

L242I/F347I I45L/C269I I180V/C208S F267Y/N148R Q280R/C44F

L242I/V221F I45L/D296P I180V/E240A F267Y/K361R Q280R/C44Y

L242I/V221I I45L/F140Y I180V/E240T F267Y/Q280E Q280R/I3L

L242I/G245S I45L/I24L I180V/N148H F267Y/Q280R Q280R/I3M

L242I/Q92C I45L/I24V I180V/F94L F267Y/K225E K225E/K225G

L242I/Q92S I45L/D170S I180V/F94Y F267Y/K225G K225E/L238A

L242I/F230A I45L/V229M I180V/V150L F267Y/L238A K225E/L238S

L242I/F230N I45L/E360A I180V/F68P F267Y/L238S K225E/C269A

L242I/ S87P I45L/ S322V I180V/N148R F267Y/C269A K225E/C269I

L242I/ S87Q I45L/F347I I180V/K361R F267Y/C269I K225E/D296P

L242I/L98H I45L/V221F I180V/Q280E F267Y/D296P K225E/F140Y

L242I/ S70K I45L/V221I I180V/Q280R F267Y/F140Y K225E/I24L

L242I/F351A I45L/G245S I180V/K225E F267Y/I24L K225E/I24V

L242I/F351V I45L/Q92C I180V/K225G F267Y/I24V K225E/D170S

L242I/M157Y I45L/Q92S I180V/L238A F267Y/D170S K225E/V229M

L242I/C44F I45L/F230A I180V/L238S F267Y/V229M K225E/E360A

L242I/C44Y I45L/F230N I180V/C269A F267Y/E360A K225E/ S322V

L242I/I3L I45L/ S87P I180V/C269I F267Y/ S322V K225E/F347I

L242I/I3M I45L/ S87Q I180V/D296P F267Y/F347I K225E/V221F

Q108H/F68V I45L/L98H I180V/F140Y F267Y/V221F K225E/V221I

Q108H/G100S I45L/ S70K I180V/I24L F267Y/V221I K225E/G245S

Q108H/G100T I45L/F351A I180V/I24V F267Y/G245S K225E/Q92C

Q108H/L323I I45L/F351V I180V/D170S F267Y/Q92C K225E/Q92S

Q108H/L323M I45L/M157Y I180V/V229M F267Y/Q92S K225E/F230A

Q108H/Q277D I45L/C44F I180V/E360A F267Y/F230A K225E/F230N

Q108H/Q277E I45L/C44Y I180V/ S322V F267Y/F230N K225E/ S87P

Q108H/C269N I45L/I3L I180V/F347I F267Y/ S87P K225E/ S87Q

Q108H/C269T I45L/I3M I180V/V221F F267Y/ S87Q K225E/L98H

Q108H/A326F E258A/A272E I180V/V221I F267Y/L98H K225E/ S70K

Q108H/A326I E258A/T312A I180V/G245S F267Y/ S70K K225E/F351A

Q108H/L152F E258A/T312R I180V/Q92C F267Y/F351A K225E/F351V

Q108H/C282N E258A/M327Q I180V/Q92S F267Y/F351V K225E/M157Y

Q108H/ S329P E258A/M327T I180V/F230A F267Y/M157Y K225E/C44F

Q108H/I45D E258A/N174Y I180V/F230N F267Y/C44F K225E/C44Y

Q108H/I45L E258A/L340I I180V/ S87P F267Y/C44Y K225E/I3L

Q108H/E258A E258A/L340M I180V/ S87Q F267Y/I3L K225E/I3M

Q108H/A272E E258A/A189H I180V/L98H F267Y/I3M K225G/L238A

Q108H/T312A E258A/A189Y I180V/ S70K E71N/E252Q K225G/L238S Positions Positions Positions Positions Positions

Q108H/T312R E258A/N194R I180V/F351A E71N/I367V K225G/C269A

Q108H/M327Q E258A/N194S I180V/F351V E71N/A31M K225G/C269I

Q108H/M327T E258A/L169V I180V/M157Y E71N/A31 S K225G/D296P

Q108H/N174Y E258A/K225D I180V/C44F E71N/F93A K225G/F140Y

Q108H/L340I E258A/K225S I180V/C44Y E71N/L323C K225G/I24L

Q108H/L340M E258A/A63I I180V/I3L E71N/L323V K225G/I24V

Q108H/A189H E258A/A63P I180V/I3M E71N/T83G K225G/D170S

Q108H/A189Y E258A/I180L H151D /T220I E71N/T83N K225G/V229M

Q108H/N194R E258A/I180V H151D /T220S E71N/Q92R K225G/E360A

Q108H/N194S E258A/H151D H151D /L246I E71N/F267I K225G/ S322V

Q108H/L169V E258A/T220I H151D/A272P E71N/F267Q K225G/F347I

Q108H/K225D E258A/T220S H151D / S353E E71N/E4K K225G/V221F

Q108H/K225S E258A/L246I H151D/ S353K E71N/E90D K225G/V221I

Q108H/A63I E258A/A272P H151D /A256D E71N/T312K K225G/G245S

Q108H/A63P E258A/ S353E H151D/A256E E71N/T312N K225G/Q92C

Q108H/I180L E258A/ S353K H151D/R224L E71N/L241V K225G/Q92S

Q108H/I180V E258A/A256D H151D /A134M E71N/V255I K225G/F230A

Q108H/H151D E258A/A256E H151D/V359E E71N/F344G K225G/F230N

Q108H/T220I E258A/R224L H151D /V359K E71N/I76L K225G/ S87P

Q108H/T220S E258A/A134M H151D/ S333A E71N/I76M K225G/ S87Q

Q108H/L246I E258A/V359E H151D / S333E E71N/G138K K225G/L98H

Q108H/A272P E258A/V359K H151D/T352D E71N/L238F K225G/ S70K

Q108H/ S353E E258A/ S333A H151D /T352E E71N/L238T K225G/F351A

Q108H/ S353K E258A/ S333E H151D/M157F E71N/I35L K225G/F351V

Q108H/A256D E258A/T352D H151D/M157S E71N/I35V K225G/M157Y

Q108H/A256E E258A/T352E H151D/D14G E71N/C208A K225G/C44F

Q108H/R224L E258A/M157F H151D /D296A E71N/C208S K225G/C44Y

Q108H/A134M E258A/M157S H151D/D296L E71N/E240A K225G/I3L

Q108H/V359E E258A/D14G H151D/T314A E71N/E240T K225G/I3M

Q108H/V359K E258A/D296A H151D /T314E E71N/N148H L238A/L238S

Q108H/ S333A E258A/D296L H151D/F267Y E71N/F94L L238A/C269A

Q108H/ S333E E258A/T314A H151D /E71N E71N/F94Y L238A/C269I

Q108H/T352D E258A/T314E H151D/E252Q E71N/V150L L238A/D296P

Q108H/T352E E258A/F267Y H151D/I367V E71N/F68P L238A/F140Y

Q108H/M157F E258A/E71N H151D/A31M E71N/N148R L238A/I24L

Q108H/M157S E258A/E252Q H151D /A31 S E71N/K361R L238A/I24V

Q108H/D14G E258A/I367V H151D /F93A E71N/Q280E L238A/D170S

Q108H/D296A E258A/A31M H151D/L323C E71N/Q280R L238A/V229M

Q108H/D296L E258A/A31 S H151D/L323V E71N/K225E L238A/E360A

Q108H/T314A E258A/F93A H151D /T83G E71N/K225G L238A/ S322V

Q108H/T314E E258A/L323C H151D /T83N E71N/L238A L238A/F347I

Q108H/F267Y E258A/L323V H151D/Q92R E71N/L238S L238A/V221F Positions Positions Positions Positions Positions

Q108H/E71N E258A/T83G H151D/F267I E71N/C269A L238A/V221I

Q108H/E252Q E258A/T83N H151D/F267Q E71N/C269I L238A/G245S

Q108H/I367V E258A/Q92R H151D/E4K E71N/D296P L238A/Q92C

Q108H/A31M E258A/F267I H151D/E90D E71N/F140Y L238A/Q92S

Q108H/A31S E258A/F267Q H151D/T312K E71N/I24L L238A/F230A

Q108H/F93A E258A/E4K H151D/T312N E71N/I24V L238A/F230N

Q108H/L323C E258A/E90D H151D/L241V E71N/D170S L238A/S87P

Q108H/L323V E258A/T312K H151D/V255I E71N/V229M L238A/S87Q

Q108H/T83G E258A/T312N H151D/F344G E71N/E360A L238A/L98H

Q108H/T83N E258A/L241V H151D/I76L E71N/S322V L238A/S70K

Q108H/Q92R E258A/V255I H151D/I76M E71N/F347I L238A/F351A

Q108H/F267I E258A/F344G H151D/G138K E71N/V221F L238A/F351V

Q108H/F267Q E258A/I76L H151D/L238F E71N/V221I L238A/M157Y

Q108H/E4K E258A/I76M H151D/L238T E71N/G245S L238A/C44F

Q108H/E90D E258A/G138K H151D/I35L E71N/Q92C L238A/C44Y

Q108H/T312K E258A/L238F H151D/I35V E71N/Q92S L238A/I3L

Q108H/T312N E258A/L238T H151D/C208A E71N/F230A L238A/I3M

Q108H/L241V E258A/I35L H151D/C208S E71N/F230N L238S/C269A

Q108H/V255I E258A/I35V H151D/E240A E71N/S87P L238S/C269I

Q108H/F344G E258A/C208A H151D/E240T E71N/S87Q L238S/D296P

Q108H/I76L E258A/C208S H151D/N148H E71N/L98H L238S/F140Y

Q108H/I76M E258A/E240A H151D/F94L E71N/S70K L238S/I24L

Q108H/G138K E258A/E240T H151D/F94Y E71N/F351A L238S/I24V

Q108H/L238F E258A/N148H H151D/V150L E71N/F351V L238S/D170S

Q108H/L238T E258A/F94L H151D/F68P E71N/M157Y L238S/V229M

Q108H/I35L E258A/F94Y H151D/N148R E71N/C44F L238S/E360A

Q108H/I35V E258A/V150L H151D/K361R E71N/C44Y L238S/S322V

Q108H/C208A E258A/F68P H151D/Q280E E71N/I3L L238S/F347I

Q108H/C208S E258A/N148R H151D/Q280R E71N/I3M L238S/V221F

Q108H/E240A E258A/K361R H151D/K225E E252Q/I367V L238S/V221I

Q108H/E240T E258A/Q280E H151D/K225G E252Q/A31M L238S/G245S

Q108H/N148H E258A/Q280R H151D/L238A E252Q/A31S L238S/Q92C

Q108H/F94L E258A/K225E H151D/L238S E252Q/F93A L238S/Q92S

Q108H/F94Y E258A/K225G H151D/C269A E252Q/L323C L238S/F230A

Q108H/V150L E258A/L238A H151D/C269I E252Q/L323V L238S/F230N

Q108H/F68P E258A/L238S H151D/D296P E252Q/T83G L238S/S87P

Q108H/N148R E258A/C269A H151D/F140Y E252Q/T83N L238S/S87Q

Q108H/K361R E258A/C269I H151D/I24L E252Q/Q92R L238S/L98H

Q108H/Q280E E258A/D296P H151D/I24V E252Q/F267I L238S/S70K

Q108H/Q280R E258A/F140Y H151D/D170S E252Q/F267Q L238S/F351A

Q108H/K225E E258A/I24L H151D/V229M E252Q/E4K L238S/F351V

Q108H/K225G E258A/I24V H151D/E360A E252Q/E90D L238S/M157Y Positions Positions Positions Positions Positions

Q108H/L238A E258A/D170S H151D/ S322V E252Q /T312K L238S /C44F

Q108H/L238S E258A/V229M H151D/F347I E252Q /T312N L238S /C44Y

Q108H/C269A E258A/E360A H151D/V221F E252Q /L241V L238S /I3L

Q108H/C269I E258A/ S322V H151D/V221I E252Q/V255I L238S /I3M

Q108H/D296P E258A/F347I H151D/G245S E252Q/F344G C269A/C269I

Q108H/F140Y E258A/V221F H151D/Q92C E252Q/I76L C269A/D296P

Q108H/I24L E258A/V221I H151D /Q92S E252Q /I76M C269A/F140Y

Q108H/I24V E258A/G245S H151D/F230A E252Q/G138K C269A/I24L

Q108H/D170S E258A/Q92C H151D/F230N E252Q /L238F C269A/I24V

Q108H/V229M E258A/Q92S H151D / S87P E252Q/L238T C269A/D170S

Q108H/E360A E258A/F230A H151D / S87Q E252Q/I35L C269A/V229M

Q108H/ S322V E258A/F230N H151D /L98H E252Q /I35V C269A/E360A

Q108H/F347I E258A/ S87P H151D / S70K E252Q/C208A C269A/ S322V

Q108H/V221F E258A/ S87Q H151D/F351A E252Q/C208S C269A/F347I

Q108H/V221I E258A/L98H H151D/F351V E252Q /E240A C269A/V221F

Q108H/G245S E258A/ S70K H151D /M157Y E252Q/E240T C269A/V221I

Q108H/Q92C E258A/F351A H151D/C44F E252Q/N148H C269A/G245S

Q108H/Q92S E258A/F351V H151D/C44Y E252Q /F94L C269A/Q92C

Q108H/F230A E258A/M157Y H151D /I3L E252Q/F94Y C269A/Q92S

Q108H/F230N E258A/C44F H151D /I3M E252Q /V150L C269A/F230A

Q108H/ S87P E258A/C44Y T220I/T220S E252Q/F68P C269A/F230N

Q108H/ S87Q E258A/I3L T220I/L246I E252Q/N148R C269A/ S87P

Q108H/L98H E258A/I3M T220I/A272P E252Q/K361R C269A/ S87Q

Q108H/ S70K A272E/T312A T220I/ S353E E252Q /Q280E C269A/L98H

Q108H/F351A A272E/T312R T220I/ S353K E252Q/Q280R C269A/ S70K

Q108H/F351V A272E/M327Q T220I/A256D E252Q /K225E C269A/F351A

Q108H/M157Y A272E/M327T T220I/A256E E252Q/K225G C269A/F351V

Q108H/C44F A272E/N174Y T220I/R224L E252Q/L238A C269A/M157Y

Q108H/C44Y A272E/L340I T220I/A134M E252Q /L238S C269A/C44F

Q108H/I3L A272E/L340M T220I/V359E E252Q/C269A C269A/C44Y

Q108H/I3M A272E/A189H T220I/V359K E252Q/C269I C269A/I3L

F68V/G100S A272E/A189Y T220I/ S333A E252Q /D296P C269A/I3M

F68V/G100T A272E/N194R T220I/ S333E E252Q/F140Y C269I/D296P

F68V/L323I A272E/N194S T220I/T352D E252Q/I24L C269I/F140Y

F68V/L323M A272E/L169V T220I/T352E E252Q /I24V C269I/I24L

F68V/Q277D A272E/K225D T220I/M157F E252Q /D170S C269I/I24V

F68V/Q277E A272E/K225S T220I/M157S E252Q/V229M C269I/D170S

F68V/C269N A272E/A63I T220I/D14G E252Q /E360A C269I/V229M

F68V/C269T A272E/A63P T220I/D296A E252Q/ S322V C269I/E360A

F68V/A326F A272E/I180L T220I/D296L E252Q/F347I C269I/ S322V

F68V/A326I A272E/I180V T220I/T314A E252Q /V221F C269I/F347I

F68V/L152F A272E/H151D T220I/T314E E252Q/V221I C269I/V221F Positions Positions Positions Positions Positions

F68V/C282N A272E/T220I T220I/F267Y E252Q /G245S C269I/V221I

F68V/ S329P A272E/T220S T220I/E71N E252Q /Q92C C269I/G245S

F68V/I45D A272E/L246I T220I/E252Q E252Q/Q92S C269I/Q92C

F68V/I45L A272E/A272P T220I/I367V E252Q/F230A C269I/Q92S

F68V/E258A A272E/ S353E T220I/A31M E252Q/F230N C269I/F230A

F68V/A272E A272E/ S353K T220I/A31 S E252Q/ S87P C269I/F230N

F68V/T312A A272E/A256D T220I/F93A E252Q/ S87Q C269I/ S87P

F68V/T312R A272E/A256E T220I/L323C E252Q/L98H C269I/ S87Q

F68V/M327Q A272E/R224L T220I/L323V E252Q/ S70K C269I/L98H

F68V/M327T A272E/A134M T220I/T83G E252Q/F351A C269I/ S70K

F68V/N174Y A272E/V359E T220I/T83N E252Q/F351V C269I/F351A

F68V/L340I A272E/V359K T220I/Q92R E252Q/M157Y C269I/F351V

F68V/L340M A272E/ S333A T220I/F267I E252Q /C44F C269I/M157Y

F68V/A189H A272E/ S333E T220I/F267Q E252Q /C44Y C269I/C44F

F68V/A189Y A272E/T352D T220I/E4K E252Q /I3L C269I/C44Y

F68V/N194R A272E/T352E T220I/E90D E252Q/I3M C269I/I3L

F68V/N194S A272E/M157F T220I/T312K I367V/A31M C269I/I3M

F68V/L169V A272E/M157S T220I/T312N I367V/A31 S D296P/F140Y

F68V/K225D A272E/D14G T220I/L241V I367V/F93A D296P/I24L

F68V/K225S A272E/D296A T220I/V255I I367V/L323C D296P/I24V

F68V/A63I A272E/D296L T220I/F344G I367V/L323V D296P/D170S

F68V/A63P A272E/T314A T220I/I76L I367V/T83G D296P/V229M

F68V/I180L A272E/T314E T220I/I76M I367V/T83N D296P/E360A

F68V/I180V A272E/F267Y T220I/G138K I367V/Q92R D296P/ S322V

F68V/H151D A272E/E71N T220I/L238F I367V/F267I D296P/F347I

F68V/T220I A272E/E252Q T220I/L238T I367V/F267Q D296P/V221F

F68V/T220S A272E/I367V T220I/I35L I367V/E4K D296P/V221I

F68V/L246I A272E/A31M T220I/I35V I367V/E90D D296P/G245S

F68V/A272P A272E/A31 S T220I/C208A I367V/T312K D296P/Q92C

F68V/ S353E A272E/F93A T220I/C208S I367V/T312N D296P/Q92S

F68V/ S353K A272E/L323C T220I/E240A I367V/L241V D296P/F230A

F68V/A256D A272E/L323V T220I/E240T I367V/V255I D296P/F230N

F68V/A256E A272E/T83G T220I/N148H I367V/F344G D296P/ S87P

F68V/R224L A272E/T83N T220I/F94L I367V/I76L D296P/ S87Q

F68V/A134M A272E/Q92R T220I/F94Y I367V/I76M D296P/L98H

F68V/V359E A272E/F267I T220I/V150L I367V/G138K D296P/ S70K

F68V/V359K A272E/F267Q T220I/F68P I367V/L238F D296P/F351A

F68V/ S333A A272E/E4K T220I/N148R I367V/L238T D296P/F351V

F68V/ S333E A272E/E90D T220I/K361R I367V/I35L D296P/M157Y

F68V/T352D A272E/T312K T220I/Q280E 1367V / 135 V D296P/C44F

F68V/T352E A272E/T312N T220I/Q280R I367V/C208A D296P/C44Y

F68V/M157F A272E/L241V T220I/K225E I367V/C208S D296P/I3L Positions Positions Positions Positions Positions

F68V/M157S A272E/V255I T220I/K225G I367V/E240A D296P/I3M

F68V/D14G A272E/F344G T220I/L238A I367V/E240T F140Y/I24L

F68V/D296A A272E/I76L T220I/L238S I367V/N148H F140Y/I24V

F68V/D296L A272E/I76M T220I/C269A I367V/F94L F140Y/D170S

F68V/T314A A272E/G138K T220I/C269I I367V/F94Y F140Y/V229M

F68V/T314E A272E/L238F T220I/D296P I367V/V150L F140Y/E360A

F68V/F267Y A272E/L238T T220I/F140Y I367V/F68P F140Y/ S322V

F68V/E71N A272E/I35L T220I/I24L I367V/N148R F140Y/F347I

F68V/E252Q A272E/I35V T220I/I24V I367V/K361R F140Y/V221F

F68V/I367V A272E/C208A T220I/D170S I367V/Q280E F140Y/V221I

F68V/A31M A272E/C208S T220I/V229M I367V/Q280R F140Y/G245S

F68V/A31 S A272E/E240A T220I/E360A I367V/K225E F140Y/Q92C

F68V/F93A A272E/E240T T220I/ S322V I367V/K225G F140Y/Q92S

F68V/L323C A272E/N148H T220I/F347I I367V/L238A F140Y/F230A

F68V/L323V A272E/F94L T220I/V221F I367V/L238S F140Y/F230N

F68V/T83G A272E/F94Y T220I/V221I I367V/C269A F140Y/ S87P

F68V/T83N A272E/V150L T220I/G245S I367V/C269I F140Y/ S87Q

F68V/Q92R A272E/F68P T220I/Q92C I367V/D296P F140Y/L98H

F68V/F267I A272E/N148R T220I/Q92S I367V/F140Y F140Y/ S70K

F68V/F267Q A272E/K361R T220I/F230A I367V/I24L F140Y/F351A

F68V/E4K A272E/Q280E T220I/F230N I367V/I24V F140Y/F351V

F68V/E90D A272E/Q280R T220I/ S87P I367V/D170S F140Y/M157Y

F68V/T312K A272E/K225E T220I/ S87Q I367V/V229M F140Y/C44F

F68V/T312N A272E/K225G T220I/L98H I367V/E360A F140Y/C44Y

F68V/L241V A272E/L238A T220I/ S70K I367V/ S322V F140Y/I3L

F68V/V255I A272E/L238S T220I/F351A I367V/F347I F140Y/I3M

F68V/F344G A272E/C269A T220I/F351V I367V/V221F I24L/I24V

F68V/I76L A272E/C269I T220I/M157Y I367V/V221I I24L/D170S

F68V/I76M A272E/D296P T220I/C44F I367V/G245S I24L/V229M

F68V/G138K A272E/F140Y T220I/C44Y I367V/Q92C I24L/E360A

F68V/L238F A272E/I24L T220I/I3L I367V/Q92S I24L/ S322V

F68V/L238T A272E/I24V T220I/I3M I367V/F230A I24L/F347I

F68V/I35L A272E/D170S T220S /L246I I367V/F230N I24L/V221F

F68V/I35V A272E/V229M T220S /A272P I367V/ S87P I24L/V221I

F68V/C208A A272E/E360A T220S / S353E I367V/ S87Q I24L/G245S

F68V/C208S A272E/ S322V T220S / S353K I367V/L98H I24L/Q92C

F68V/E240A A272E/F347I T220S /A256D I367V/ S70K I24L/Q92S

F68V/E240T A272E/V221F T220S /A256E I367V/F351A I24L/F230A

F68V/N148H A272E/V221I T220S /R224L I367V/F351V I24L/F230N

F68V/F94L A272E/G245S T220S /A134M I367V/M157Y I24L/ S87P

F68V/F94Y A272E/Q92C T220S /V359E I367V/C44F I24L/ S87Q

F68V/V150L A272E/Q92S T220S /V359K I367V/C44Y I24L/L98H Positions Positions Positions Positions Positions

F68V/F68P A272E/F230A T220S/S333A I367V/I3L I24L/S70K

F68V/N148R A272E/F230N T220S/S333E I367V/I3M I24L/F351A

F68V/K361R A272E/S87P T220S/T352D A31M/A31S I24L/F351V

F68V/Q280E A272E/S87Q T220S/T352E A31M/F93A I24L/M157Y

F68V/Q280R A272E/L98H T220S/M157F A31M/L323C I24L/C44F

F68V/K225E A272E/S70K T220S/M157S A31M/L323V I24L/C44Y

F68V/K225G A272E/F351A T220S/D14G A31M/T83G I24L/I3L

F68V/L238A A272E/F351V T220S/D296A A31M/T83N I24L/I3M

F68V/L238S A272E/M157Y T220S/D296L A31M/Q92R I24V/D170S

F68V/C269A A272E/C44F T220S/T314A A31M/F267I I24V/V229M

F68V/C269I A272E/C44Y T220S/T314E A31M/F267Q I24V/E360A

F68V/D296P A272E/I3L T220S/F267Y A31M/E4K I24V/S322V

F68V/F140Y A272E/I3M T220S/E71N A31M/E90D I24V/F347I

F68V/I24L T312A/T312R T220S/E252Q A31M/T312K I24V/V221F

F68V/I24V T312A/M327Q T220S/I367V A31M/T312N I24V/V221I

F68V/D170S T312A/M327T T220S/A31M A31M/L241V I24V/G245S

F68V/V229M T312A/N174Y T220S/A31S A31M/V255I I24V/Q92C

F68V/E360A T312A/L340I T220S/F93A A31M/F344G I24V/Q92S

F68V/S322V T312A/L340M T220S/L323C A31M/I76L I24V/F230A

F68V/F347I T312A/A189H T220S/L323V A31M/I76M I24V/F230N

F68V/V221F T312A/A189Y T220S/T83G A31M/G138K I24V/S87P

F68V/V221I T312A/N194R T220S/T83N A31M/L238F I24V/S87Q

F68V/G245S T312A/N194S T220S/Q92R A31M/L238T I24V/L98H

F68V/Q92C T312A/L169V T220S/F267I A31M/I35L I24V/S70K

F68V/Q92S T312A/K225D T220S/F267Q A31M/I35V I24V/F351A

F68V/F230A T312A/K225S T220S/E4K A31M/C208A I24V/F351V

F68V/F230N T312A/A63I T220S/E90D A31M/C208S I24V/M157Y

F68V/S87P T312A/A63P T220S/T312K A31M/E240A I24V/C44F

F68V/S87Q T312A/I180L T220S/T312N A31M/E240T I24V/C44Y

F68V/L98H T312A/I180V T220S/L241V A31M/N148H I24V/I3L

F68V/S70K T312A/H151D T220S/V255I A31M/F94L I24V/I3M

F68V/F351A T312A/T220I T220S/F344G A31M/F94Y D170S/V229M

F68V/F351V T312A/T220S T220S/I76L A31M/V150L D170S/E360A

F68V/M157Y T312A/L246I T220S/I76M A31M/F68P D170S/S322V

F68V/C44F T312A/A272P T220S/G138K A31M/N148R D170S/F347I

F68V/C44Y T312A/S353E T220S/L238F A31M/K361R D170S/V221F

F68V/I3L T312A/S353K T220S/L238T A31M/Q280E D170S/V221I

F68V/I3M T312A/A256D T220S/I35L A31M/Q280R D170S/G245S

G100S/G100T T312A/A256E T220S/I35V A31M/K225E D170S/Q92C

G100S/L323I T312A/R224L T220S/C208A A31M/K225G D170S/Q92S

G100S/L323M T312A/A134M T220S/C208S A31M/L238A D170S/F230A

G100S/Q277D T312A/V359E T220S/E240A A31M/L238S D170S/F230N Positions Positions Positions Positions Positions

G100S/Q277E T312A/V359K T220S/E240T A31M/C269A D170S/S87P

G100S/C269N T312A/S333A T220S/N148H A31M/C269I D170S/S87Q

G100S/C269T T312A/S333E T220S/F94L A31M/D296P D170S/L98H

G100S/A326F T312A/T352D T220S/F94Y A31M/F140Y D170S/S70K

G100S/A326I T312A/T352E T220S/V150L A31M/I24L D170S/F351A

G100S/L152F T312A/M157F T220S/F68P A31M/I24V D170S/F351V

G100S/C282N T312A/M157S T220S/N148R A31M/D170S D170S/M157Y

G100S/S329P T312A/D14G T220S/K361R A31M/V229M D170S/C44F

G100S/I45D T312A/D296A T220S/Q280E A31M/E360A D170S/C44Y

G100S/I45L T312A/D296L T220S/Q280R A31M/S322V D170S/I3L

G100S/E258A T312A/T314A T220S/K225E A31M/F347I D170S/I3M

G100S/A272E T312A/T314E T220S/K225G A31M/V221F V229M/E360A

G100S/T312A T312A/F267Y T220S/L238A A31M/V221I V229M/S322V

G100S/T312R T312A/E71N T220S/L238S A31M/G245S V229M/F347I

G100S/M327Q T312A/E252Q T220S/C269A A31M/Q92C V229M/V221F

G100S/M327T T312A/I367V T220S/C269I A31M/Q92S V229M/V221I

G100S/N174Y T312A/A31M T220S/D296P A31M/F230A V229M/G245S

G100S/L340I T312A/A31S T220S/F140Y A31M/F230N V229M/Q92C

G100S/L340M T312A/F93A T220S/I24L A31M/S87P V229M/Q92S

G100S/A189H T312A/L323C T220S/I24V A31M/S87Q V229M/F230A

G100S/A189Y T312A/L323V T220S/D170S A31M/L98H V229M/F230N

G100S/N194R T312A/T83G T220S/V229M A31M/S70K V229M/S87P

G100S/N194S T312A/T83N T220S/E360A A31M/F351A V229M/S87Q

G100S/L169V T312A/Q92R T220S/S322V A31M/F351V V229M/L98H

G100S/K225D T312A/F267I T220S/F347I A31M/M157Y V229M/S70K

G100S/K225S T312A/F267Q T220S/V221F A31M/C44F V229M/F351A

G100S/A63I T312A/E4K T220S/V221I A31M/C44Y V229M/F351V

G100S/A63P T312A/E90D T220S/G245S A31M/I3L V229M/M157Y

G100S/I180L T312A/T312K T220S/Q92C A31M/I3M V229M/C44F

G100S/I180V T312A/T312N T220S/Q92S A31S/F93A V229M/C44Y

G100S/H151D T312A/L241V T220S/F230A A31S/L323C V229M/I3L

G100S/T220I T312A/V255I T220S/F230N A31S/L323V V229M/I3M

G100S/T220S T312A/F344G T220S/S87P A31S/T83G E360A/S322V

G100S/L246I T312A/I76L T220S/S87Q A31S/T83N E360A/F347I

G100S/A272P T312A/I76M T220S/L98H A31S/Q92R E360A/V221F

G100S/S353E T312A/G138K T220S/S70K A31S/F267I E360A/V221I

G100S/S353K T312A/L238F T220S/F351A A31S/F267Q E360A/G245S

G100S/A256D T312A/L238T T220S/F351V A31S/E4K E360A/Q92C

G100S/A256E T312A/I35L T220S/M157Y A31S/E90D E360A/Q92S

G100S/R224L T312A/I35V T220S/C44F A31S/T312K E360A/F230A

G100S/A134M T312A/C208A T220S/C44Y A31S/T312N E360A/F230N

G100S/V359E T312A/C208S T220S/I3L A31S/L241V E360A/S87P Positions Positions Positions Positions Positions

G100S/V359K T312A/E240A T220S/I3M A31S/V255I E360A/S87Q

G100S/S333A T312A/E240T L246I/A272P A31S/F344G E360A/L98H

G100S/S333E T312A/N148H L246I/S353E A31S/I76L E360A/S70K

G100S/T352D T312A/F94L L246I/S353K A31S/I76M E360A/F351A

G100S/T352E T312A/F94Y L246I/A256D A31S/G138K E360A/F351V

G100S/M157F T312A/V150L L246I/A256E A31S/L238F E360A/M157Y

G100S/M157S T312A/F68P L246I/R224L A31S/L238T E360A/C44F

G100S/D14G T312A/N148R L246I/A134M A31S/I35L E360A/C44Y

G100S/D296A T312A/K361R L246I/V359E A31S/I35V E360A/I3L

G100S/D296L T312A/Q280E L246I/V359K A31S/C208A E360A/I3M

G100S/T314A T312A/Q280R L246I/S333A A31S/C208S S322V/F347I

G100S/T314E T312A/K225E L246I/S333E A31S/E240A S322V/V221F

G100S/F267Y T312A/K225G L246I/T352D A31S/E240T S322V/V221I

G100S/E71N T312A/L238A L246I/T352E A31S/N148H S322V/G245S

G100S/E252Q T312A/L238S L246I/M157F A31S/F94L S322V/Q92C

G100S/I367V T312A/C269A L246I/M157S A31S/F94Y S322V/Q92S

G100S/A31M T312A/C269I L246I/D14G A31S/V150L S322V/F230A

G100S/A31S T312A/D296P L246I/D296A A31S/F68P S322V/F230N

G100S/F93A T312A/F140Y L246I/D296L A31S/N148R S322V/S87P

G100S/L323C T312A/I24L L246I/T314A A31S/K361R S322V/S87Q

G100S/L323V T312A/I24V L246I/T314E A31S/Q280E S322V/L98H

G100S/T83G T312A/D170S L246I/F267Y A31S/Q280R S322V/S70K

G100S/T83N T312A/V229M L246I/E71N A31S/K225E S322V/F351A

G100S/Q92R T312A/E360A L246I/E252Q A31S/K225G S322V/F351V

G100S/F267I T312A/S322V L246I/I367V A31S/L238A S322V/M157Y

G100S/F267Q T312A/F347I L246I/A31M A31S/L238S S322V/C44F

G100S/E4K T312A/V221F L246I/A31S A31S/C269A S322V/C44Y

G100S/E90D T312A/V221I L246I/F93A A31S/C269I S322V/I3L

G100S/T312K T312A/G245S L246I/L323C A31S/D296P S322V/I3M

G100S/T312N T312A/Q92C L246I/L323V A31S/F140Y F347I/V221F

G100S/L241V T312A/Q92S L246I/T83G A31S/I24L F347I/V221I

G100S/V255I T312A/F230A L246I/T83N A31S/I24V F347I/G245S

G100S/F344G T312A/F230N L246I/Q92R A31S/D170S F347I/Q92C

G100S/I76L T312A/S87P L246I/F267I A31S/V229M F347I/Q92S

G100S/I76M T312A/S87Q L246I/F267Q A31S/E360A F347I/F230A

G100S/G138K T312A/L98H L246I/E4K A31S/S322V F347I/F230N

G100S/L238F T312A/S70K L246I/E90D A31S/F347I F347I/S87P

G100S/L238T T312A/F351A L246I/T312K A31S/V221F F347I/S87Q

G100S/I35L T312A/F351V L246I/T312N A31S/V221I F347I/L98H

G100S/I35V T312A/M157Y L246I/L241V A31S/G245S F347I/S70K

G100S/C208A T312A/C44F L246I/V255I A31S/Q92C F347I/F351A

G100S/C208S T312A/C44Y L246I/F344G A31S/Q92S F347I/F351V Positions Positions Positions Positions Positions

G100S/E240A T312A/I3L L246I/I76L A31S/F230A F347I/M157Y

G100S/E240T T312A/I3M L246I/I76M A31S/F230N F347I/C44F

G100S/N148H T312R/M327Q L246I/G138K A31S/S87P F347I/C44Y

G100S/F94L T312R/M327T L246I/L238F A31S/S87Q F347I/I3L

G100S/F94Y T312R/N174Y L246I/L238T A31S/L98H F347I/I3M

G100S/V150L T312R/L340I L246I/I35L A31S/S70K V221F/V221I

G100S/F68P T312R/L340M L246I/I35V A31S/F351A V221F/G245S

G100S/N148R T312R/A189H L246I/C208A A31S/F351V V221F/Q92C

G100S/K361R T312R/A189Y L246I/C208S A31S/M157Y V221F/Q92S

G100S/Q280E T312R/N194R L246I/E240A A31S/C44F V221F/F230A

G100S/Q280R T312R/N194S L246I/E240T A31S/C44Y V221F/F230N

G100S/K225E T312R/L169V L246I/N148H A31S/I3L V221F/S87P

G100S/K225G T312R/K225D L246I/F94L A31S/I3M V221F/S87Q

G100S/L238A T312R/K225S L246I/F94Y F93A/L323C V221F/L98H

G100S/L238S T312R/A63I L246I/V150L F93A/L323V V221F/S70K

G100S/C269A T312R/A63P L246I/F68P F93A/T83G V221F/F351A

G100S/C269I T312R/I180L L246I/N148R F93A/T83N V221F/F351V

G100S/D296P T312R/I180V L246I/K361R F93A/Q92R V221F/M157Y

G100S/F140Y T312R/H151D L246I/Q280E F93A/F267I V221F/C44F

G100S/I24L T312R/T220I L246I/Q280R F93A/F267Q V221F/C44Y

G100S/I24V T312R/T220S L246I/K225E F93A/E4K V221F/I3L

G100S/D170S T312R/L246I L246I/K225G F93A/E90D V221F/I3M

G100S/V229M T312R/A272P L246I/L238A F93A/T312K V221I/G245S

G100S/E360A T312R/S353E L246I/L238S F93A/T312N V221I/Q92C

G100S/S322V T312R/S353K L246I/C269A F93A/L241V V221I/Q92S

G100S/F347I T312R/A256D L246I/C269I F93A/V255I V221I/F230A

G100S/V221F T312R/A256E L246I/D296P F93A/F344G V221I/F230N

G100S/V221I T312R/R224L L246I/F140Y F93A/I76L V221I/S87P

G100S/G245S T312R/A134M L246I/I24L F93A/I76M V221I/S87Q

G100S/Q92C T312R/V359E L246I/I24V F93A/G138K V221I/L98H

G100S/Q92S T312R/V359K L246I/D170S F93A/L238F V221I/S70K

G100S/F230A T312R/S333A L246I/V229M F93A/L238T V221I/F351A

G100S/F230N T312R/S333E L246I/E360A F93A/I35L V221I/F351V

G100S/S87P T312R/T352D L246I/S322V F93A/I35V V221I/M157Y

G100S/S87Q T312R/T352E L246I/F347I F93A/C208A V221I/C44F

G100S/L98H T312R/M157F L246I/V221F F93A/C208S V221I/C44Y

G100S/S70K T312R/M157S L246I/V221I F93A/E240A V221I/I3L

G100S/F351A T312R/D14G L246I/G245S F93A/E240T V221I/I3M

G100S/F351V T312R/D296A L246I/Q92C F93A/N148H G245S/Q92C

G100S/M157Y T312R/D296L L246I/Q92S F93A/F94L G245S/Q92S

G100S/C44F T312R/T314A L246I/F230A F93A/F94Y G245S/F230A

G100S/C44Y T312R/T314E L246I/F230N F93A/V150L G245S/F230N Positions Positions Positions Positions Positions

G100S/I3L T312R/F267Y L246I/ S87P F93A/F68P G245S / S87P

G100S /I3M T312R/E71N L246I/ S87Q F93A/N148R G245S / S87Q

G100T/L323I T312R/E252Q L246I/L98H F93A/K361R G245S /L98H

G100T/L323M T312R/I367V L246I/ S70K F93A/Q280E G245S / S70K

G100T/Q277D T312R/A31M L246I/F351A F93A/Q280R G245S /F351A

G100T/Q277E T312R/A31 S L246I/F351V F93A/K225E G245S /F351V

G100T/C269N T312R/F93A L246I/M157Y F93A/K225G G245S /M157Y

G100T/C269T T312R/L323C L246I/C44F F93A/L238A G245S /C44F

G100T/A326F T312R/L323V L246I/C44Y F93A/L238S G245S /C44Y

G100T/A326I T312R/T83G L246I/I3L F93A/C269A G245S /I3L

G100T/L152F T312R/T83N L246I/I3M F93A/C269I G245S /I3M

G100T/C282N T312R/Q92R A272P/ S353E F93A/D296P Q92C/Q92S

G100T/ S329P T312R/F267I A272P/ S353K F93A/F140Y Q92C/F230A

G100T/I45D T312R/F267Q A272P/A256D F93A/I24L Q92C/F230N

G100T/I45L T312R/E4K A272P/A256E F93A/I24V Q92C/ S87P

G100T/E258A T312R/E90D A272P/R224L F93A/D170S Q92C/ S87Q

G100T/A272E T312R/T312K A272P/A134M F93A/V229M Q92C/L98H

G100T/T312A T312R/T312N A272P/V359E F93A/E360A Q92C/ S70K

G100T/T312R T312R/L241V A272P/V359K F93A/ S322V Q92C/F351A

G100T/M327Q T312R/V255I A272P/ S333A F93A/F347I Q92C/F351V

G100T/M327T T312R/F344G A272P/ S333E F93A/V221F Q92C/M157Y

G100T/N174Y T312R/I76L A272P/T352D F93A/V221I Q92C/C44F

G100T/L340I T312R/I76M A272P/T352E F93A/G245S Q92C/C44Y

G100T/L340M T312R/G138K A272P/M157F F93A/Q92C Q92C/I3L

G100T/A189H T312R/L238F A272P/M157S F93A/Q92S Q92C/I3M

G100T/A189Y T312R/L238T A272P/D14G F93A/F230A Q92S /F230A

G100T/N194R T312R/I35L A272P/D296A F93A/F230N Q92S /F230N

G100T/N194S T312R/I35V A272P/D296L F93A/ S87P Q92S / S87P

G100T/L169V T312R/C208A A272P/T314A F93A/ S87Q Q92S / S87Q

G100T/K225D T312R/C208S A272P/T314E F93A/L98H Q92S /L98H

G100T/K225S T312R/E240A A272P/F267Y F93A/ S70K Q92S / S70K

G100T/A63I T312R/E240T A272P/E71N F93A/F351A Q92S /F351A

G100T/A63P T312R/N148H A272P/E252Q F93A/F351V Q92S /F351V

G100T/I180L T312R/F94L A272P/I367V F93A/M157Y Q92S /M157Y

G100T/I180V T312R/F94Y A272P/A31M F93A/C44F Q92S/C44F

G100T/H151D T312R/V150L A272P/A31 S F93A/C44Y Q92S /C44Y

G100T/T220I T312R/F68P A272P/F93A F93A/I3L Q92S /I3L

G100T/T220S T312R/N148R A272P/L323C F93A/I3M Q92S /I3M

G100T/L246I T312R/K361R A272P/L323V L323C/L323V F230A/F230N

G100T/A272P T312R/Q280E A272P/T83G L323C/T83G F230A/ S87P

G100T/ S353E T312R/Q280R A272P/T83N L323C/T83N F230A/ S87Q

G100T/ S353K T312R/K225E A272P/Q92R L323C/Q92R F230A/L98H Positions Positions Positions Positions Positions

G100T/A256D T312R/K225G A272P/F267I L323C/F267I F230A/ S70K

G100T/A256E T312R/L238A A272P/F267Q L323C/F267Q F230A/F351A

G100T/R224L T312R/L238S A272P/E4K L323C/E4K F230A/F351V

G100T/A134M T312R/C269A A272P/E90D L323C/E90D F230A/M157Y

G100T/V359E T312R/C269I A272P/T312K L323C/T312K F230A/C44F

G100T/V359K T312R/D296P A272P/T312N L323C/T312N F230A/C44Y

G100T/ S333A T312R/F140Y A272P/L241V L323C/L241V F230A/I3L

G100T/ S333E T312R/I24L A272P/V255I L323C/V255I F230A/I3M

G100T/T352D T312R/I24V A272P/F344G L323C/F344G F230N/ S87P

G100T/T352E T312R/D170S A272P/I76L L323C/I76L F230N/ S87Q

G100T/M157F T312R/V229M A272P/I76M L323C/I76M F230N/L98H

G100T/M157S T312R/E360A A272P/G138K L323C/G138K F230N/ S70K

G100T/D14G T312R/ S322V A272P/L238F L323C/L238F F230N/F351A

G100T/D296A T312R/F347I A272P/L238T L323C/L238T F230N/F351V

G100T/D296L T312R/V221F A272P/I35L L323C/I35L F230N/M157Y

G100T/T314A T312R/V221I A272P/I35V L323C/I35V F230N/C44F

G100T/T314E T312R/G245S A272P/C208A L323C/C208A F230N/C44Y

G100T/F267Y T312R/Q92C A272P/C208S L323C/C208S F230N/I3L

G100T/E71N T312R/Q92S A272P/E240A L323C/E240A F230N/I3M

G100T/E252Q T312R/F230A A272P/E240T L323C/E240T S87P/ S87Q

G100T/I367V T312R/F230N A272P/N148H L323C/N148H S87P/L98H

G100T/A31M T312R/ S87P A272P/F94L L323C/F94L S87P/ S70K

G100T/A31S T312R/ S87Q A272P/F94Y L323C/F94Y S87P/F351A

G100T/F93A T312R/L98H A272P/V150L L323C/V150L S87P/F351V

G100T/L323C T312R/ S70K A272P/F68P L323C/F68P S87P/M157Y

G100T/L323V T312R/F351A A272P/N148R L323C/N148R S87P/C44F

G100T/T83G T312R/F351V A272P/K361R L323C/K361R S87P/C44Y

G100T/T83N T312R/M157Y A272P/Q280E L323C/Q280E S87P/I3L

G100T/Q92R T312R/C44F A272P/Q280R L323C/Q280R S87P/I3M

G100T/F267I T312R/C44Y A272P/K225E L323C/K225E S87Q /L98H

G100T/F267Q T312R/I3L A272P/K225G L323C/K225G S87Q/ S70K

G100T/E4K T312R/I3M A272P/L238A L323C/L238A S87Q /F351A

G100T/E90D M327Q /M327T A272P/L238S L323C/L238S S87Q /F351V

G100T/T312K M327Q/N174Y A272P/C269A L323C/C269A S87Q /M157Y

G100T/T312N M327Q /L340I A272P/C269I L323C/C269I S87Q/C44F

G100T/L241V M327Q /L340M A272P/D296P L323C/D296P S87Q/C44Y

G100T/V255I M327Q/A189H A272P/F140Y L323C/F140Y S87Q/I3L

G100T/F344G M327Q/A189Y A272P/I24L L323C/I24L S87Q /I3M

G100T/I76L M327Q /N194R A272P/I24V L323C/I24V L98H/ S70K

G100T/I76M M327Q/N194S A272P/D170S L323C/D170S L98H/F351A

G100T/G138K M327Q /L169V A272P/V229M L323C/V229M L98H/F351V

G100T/L238F M327Q/K225D A272P/E360A L323C/E360A L98H/M157Y Positions Positions Positions Positions Positions

G100T/L238T M327Q/K225S A272P/ S322V L323C/ S322V L98H/C44F

G100T/I35L M327Q /A63I A272P/F347I L323C/F347I L98H/C44Y

G100T/I35V M327Q /A63P A272P/V221F L323C/V221F L98H/I3L

G100T/C208A M327Q /I180L A272P/V221I L323C/V221I L98H/I3M

G100T/C208S M327Q/I180V A272P/G245S L323C/G245S S70K/F351A

G100T/E240A M327Q/H151D A272P/Q92C L323C/Q92C S70K/F351V

G100T/E240T M327Q /T220I A272P/Q92S L323C/Q92S S70K/M157Y

G100T/N148H M327Q /T220S A272P/F230A L323C/F230A S70K/C44F

G100T/F94L M327Q /L246I A272P/F230N L323C/F230N S70K/C44Y

G100T/F94Y M327Q/A272P A272P/ S87P L323C/ S87P S70K/I3L

G100T/V150L M327Q / S353E A272P/ S87Q L323C/ S87Q S70K/I3M

G100T/F68P M327Q/ S353K A272P/L98H L323C/L98H F351A/F351V

G100T/N148R M327Q/A256D A272P/ S70K L323C/ S70K F351A/M157Y

G100T/K361R M327Q /A256E A272P/F351A L323C/F351A F351A/C44F

G100T/Q280E M327Q/R224L A272P/F351V L323C/F351V F351A/C44Y

G100T/Q280R M327Q/A134M A272P/M157Y L323C/M157Y F351A/I3L

G100T/K225E M327Q /V359E A272P/C44F L323C/C44F F351A/I3M

G100T/K225G M327Q/V359K A272P/C44Y L323C/C44Y F351V/M157Y

G100T/L238A M327Q/ S333A A272P/I3L L323C/I3L F351V/C44F

G100T/L238S M327Q / S333E A272P/I3M L323C/I3M F351V/C44Y

G100T/C269A M327Q /T352D S353E/ S353K L323V/T83G F351V/I3L

G100T/C269I M327Q/T352E S353E/A256D L323V/T83N F351V/I3M

G100T/D296P M327Q/M157F S353E/A256E L323V/Q92R M157Y/C44F

G100T/F140Y M327Q/M157S S353E/R224L L323V/F267I M157Y/C44Y

G100T/I24L M327Q /D14G S353E/A134M L323V/F267Q M157Y/I3L

G100T/I24V M327Q/D296A S353E/V359E L323V/E4K M157Y/I3M

G100T/D170S M327Q /D296L S353E/V359K L323V/E90D C44F/C44Y

G100T/V229M M327Q /T314A S353E/ S333A L323V/T312K C44F/I3L

G100T/E360A M327Q/T314E S353E/ S333E L323V/T312N C44F/I3M

G100T/ S322V M327Q/F267Y S353E/T352D L323V/L241V C44Y/I3L

G100T/F347I M327Q/E71N S353E/T352E L323V/V255I C44Y/I3M

G100T/V221F M327Q /E252Q S353E/M157F L323V/F344G I3L/I3M

G100T/V221I M327Q/I367V S353E/M157S L323V/I76L

G100T/G245S M327Q /A31M S353E/D14G L323V/I76M

G100T/Q92C M327Q /A31S S353E/D296A L323V/G138K

G100T/Q92S M327Q /F93A S353E/D296L L323V/L238F

G100T/F230A M327Q/L323C S353E/T314A L323V/L238T

G100T/F230N M327Q /L323V S353E/T314E L323V/I35L

G100T/ S87P M327Q/T83G S353E/F267Y L323V/I35V

G100T/ S87Q M327Q/T83N S353E/E71N L323V/C208A

G100T/L98H M327Q/Q92R S353E/E252Q L323V/C208S In addition to the substitutions described above, a modified MT may optionally have other substitutions, e.g., from about 1 to 30 additional substitutions, some of which may be listed in Table 1 or Table 2.

A polynucleotide encoding such a MT protein is also provided, as well as a nucleic acid construct containing the same. Since the genetic code is known, the design of such a polynucleotide is well within the skill of an artisan. The constructs may be designed to express the encoded protein when introduced into a cell and, as such, may contain an expression cassette containing the polynucleotide.

While particular embodiments of nucleic acid molecules encoding carboxyl methyltransferases are depicted as compared to the reference sequence of

SEQ ID NO:22 (alternatively, the reference sequence may be SEQ ID NO:84), within the context of the present disclosure, mention of one or more isolated nucleic acids includes variants of these sequences that are substantially similar in that they are structurally similar and encode polypeptides capable of functioning as carboxyl methyltransferases specific for one or more auxin-like herbicides. As used herein, a nucleotide sequence is deemed to be "substantially similar" if (a) a nucleotide sequence is derived from a nucleic acid molecule that encodes a carboxyl methyltransferase that retains the ability to methylate one or more auxin-like herbicides; (b) a nucleotide sequence is capable of hybridizing to the nucleotide sequences of the present disclosure under high stringency conditions; or (c) is a complement of any of the nucleic acid molecules described in (a) and (b).

"Specific for" refers to the ability of a protein {e.g., repressor, inducer) to selectively bind one or more substrate or ligand molecules. For example, a carboxyl methyltransferase of the present disclosure may be specific for substrates dicamba and 2,4-D, and for co-substrate SAM. Association or "binding" of an enzyme to a specific substrate or ligand generally involves electrostatic interactions, hydrogen bonding, Van der Waals interactions, or hydrophobic interactions. Any one of these or any combination thereof can play a role in the binding between a polypeptide and its ligand or substrate. Such a polypeptide may associate with a specific substrate or ligand with a dissociation constant (IQ) of at least 10^"6 M, 10^"7 M, 10^"8 M, 10^"9 M, 10^"10 M, 10^"11 M or 10^"12 M. Affinity and dissociation constants may be determined by one of ordinary skill in the art using well-known techniques {see Scatchard, Ann. N. Y. Acad. Sci. 57:660, 1949).

As used herein, two nucleotide sequences are said to "hybridize" or "remain hybridized" under conditions of a specified stringency when stable hybrids are formed between substantially complementary nucleic acid sequences. Stringency of hybridization refers to a description of the environment under which hybrids are annealed and washed, which typically includes ionic strength and temperature. Other factors that might affect hybridization include the probe size and the length of time the hybrids are allowed to form. For example, "high," "medium" and "low" stringency encompass the following conditions or equivalent conditions thereto: high stringency is 0.1 x SSPE or SSC, 0.1% SDS, 65°C; medium stringency is 0.2 x SSPE or SSC, 0.1% SDS, 50°C; and low stringency is 1.0 x SSPE or SSC, 0.1% SDS, 50°C.

In certain embodiments, a nucleic acid molecule encoding a carboxyl methyltransferase of this disclosure having activity on one or more auxin-like herbicides comprises a polynucleotide sequence capable of remaining hybridized under stringent conditions to a reference or wild-type carboxyl methyltransferase nucleic acid molecule, such as SEQ ID NO:22 or 84, which correspond to reference SABATH MT nucleic acid molecule sequences from Oryza sativa subspecies Indica and Oryza sativa subspecies Japonica, respectively. In other embodiments, a nucleic acid molecule encoding a carboxyl methyltransferase of this disclosure having activity on dicamba and 2,4-D with minimal or no activity on salicylic acid comprises a polynucleotide sequence capable of remaining hybridized under stringent conditions to a reference or wild-type carboxyl methyltransferase nucleic acid molecule, such as SEQ ID NO:22 or 84, which correspond to reference SABATH MT nucleic acid molecule sequences from Oryza sativa subspecies Indica and Oryza sativa subspecies Japonica, respectively.

In further embodiments, provided herein is an isolated nucleic acid molecule encoding a polypeptide having carboxyl methyltransferase activity on auxin-like herbicides, wherein (a) the nucleic acid molecule comprises a polynucleotide sequence as set forth in SEQ ID NO:22 having at least one mutation that results in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (b) the nucleic acid molecule comprises at least 90%> sequence identity with the polynucleotide sequence of (a); (c) the nucleic acid molecule encodes a polypeptide having carboxyl

methyltransferase activity and an amino acid sequence as set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (d) the nucleic acid molecule encodes a polypeptide comprising an amino acid sequence having carboxyl methyltransferase activity and at least 90%> sequence identity with a polypeptide sequence set forth in SEQ ID NO:70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; or (e) a nucleic acid molecule that hybridizes under at least high stringency conditions with (i) a full length polynucleotide of any one or more of (a) through (d) or (ii) a full length complementary strand of (i). In certain embodiments, the nucleic acid molecule further comprises a substitution mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids, and preferably has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid. In certain other embodiments, the encoded polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70, and preferably has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid.

In still further embodiments, provided herein is an isolated nucleic acid molecule encoding a polypeptide having carboxyl methyltransferase activity, wherein (a) the nucleic acid molecule comprises a polynucleotide sequence as set forth in SEQ ID NO:22 having mutations that result in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (b) the nucleic acid molecule comprises a

polynucleotide sequence having at least 90% identity to a polynucleotide of SEQ ID NO:22, 84 or 86, wherein the polynucleotide having at least 90% identity to SEQ ID NO: 86 does not have a change that alters amino acids encoded at polynucleotide position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof; (c) the nucleic acid molecule comprises a sequence encoding a polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D), minimal or no activity on salicylic acid, and an amino acid sequence as set forth in SEQ ID NO:70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; or (d) the nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-D, minimal or no activity on salicylic acid, and an amino acid sequence having at least 90%> identity with the polypeptide set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4, provided that the 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4 are not altered. In certain embodiments, the nucleic acid molecule further comprises a substitution mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids, and preferably has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid. In certain other embodiments, the encoded polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70, and preferably has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid.

In any of the aforementioned embodiments, an isolated nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity on synthetic auxinlike herbicides, minimal or no carboxyl methyltransferase activity on natural plant hormones, or both carboxyl methyltransferase activity on synthetic auxin- like herbicides and minimal or no carboxyl methyltransferase activity on natural plant hormones.

In any of the aforementioned embodiments, an isolated nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity on at least two synthetic auxin- like herbicides, or having carboxyl methyltransferase activity on two, three, four, or five synthetic auxin-like herbicides. In certain embodiments, the encoded polypeptide has carboxyl methyltransferase activity on dicamba and 2,4- dichlorophenoxyacetic acid (2,4-D), has minimal or no activity on salicylic acid, benzoic acid, indole-3-acetic acid, or any combination thereof, or has both carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid, benzoic acid, indole-3 -acetic acid, or any combination thereof.

It should be further understood that recombinant polypeptide-encoding nucleic acids could include variants of the natural sequence due to, for example, the degeneracy of the genetic code (including alleles). In certain embodiments, the reference SABATH MT nucleic acid molecule sequence is from Oryza sativa subspecies Indica (e.g. , SEQ ID NO:22), Oryza sativa subspecies Japonica (e.g., SEQ ID NO: 84), or Oryza sativa subspecies Javanica. Briefly, such "variants" may result from natural polymorphisms or may be synthesized by recombinant methodology (e.g. , to obtain codon optimization for expression in a particular host) or chemical synthesis, and may differ from wild-type polypeptides by one or more amino acid substitutions, insertions, deletions, or the like. Variants encompassing conservative amino acid substitutions include, for example, substitutions of one aliphatic amino acid for another, such as He, Val, Leu, or Ala or substitutions of one polar residue for another, such as between Lys and Arg, Glu and Asp, or Gin and Asn. Such substitutions are well known in the art to provide variants having similar physical properties and functional activities, such as for example, the ability to elicit and cross-react with similar antibodies. Other variants include nucleic acid molecules that encode a polypeptide having carboxyl methyltransferase activity and at least 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% amino acid sequence identity to a reference or wild-type carboxyl methyltransferase polypeptide, such as SEQ ID NO:70, and include from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4 (another polypeptide sequence that can be used as a reference standard is set forth in SEQ ID NO:83). In other embodiments, variants are those having greater than 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%), 96%o, 97%), 98%o, 99% or greater sequence identity with an amino acid sequence of a reference or wild-type carboxyl methyltransferase polypeptide having from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4.

As will be appreciated by those of ordinary skill in the art, a nucleic acid molecule encoding a recombinant carboxyl methyltransferase polypeptide or variant thereof may differ from a reference nucleic acid molecule due to codon degeneracy, nucleotide polymorphism, or nucleotide substitution, deletion or insertion. Thus, in certain aspects, the present disclosure includes all degenerate nucleic acid molecules that encode carboxyl methyltransferase peptides, polypeptides, and proteins of the present disclosure, which may be expressed using any nucleic acid expression system of interest. In another aspect, nucleic acid molecules that encode recombinant carboxyl methyltransferase polypeptide variants having conservative amino acid substitutions or deletions or substitutions must encode a recombinant polypeptide variant that retains at least one epitope capable of eliciting antibodies specific for the reference carboxyl methyltransferase polypeptide, or retains carboxyl methyltransferase on at least one auxin-like herbicide (in certain embodiments, retains activity against dicamba and 2,4-D).

As is known in the art, codons may be optimized for whichever host the hybrid polypeptide is to be expressed in, including without limitation bacteria, fungi, insect cells, plant cells, and mammalian cells. Additionally, codons encoding different amino acids may be changed as well, wherein one or more codons encoding different amino acids may be altered simultaneously as would best suit a particular host (e.g. , codons for arginine, glycine, leucine, and serine may all be optimized or any combination thereof). In certain embodiments, codon optimization may result in one or more changes to the primary amino acid sequence, such as a conservative amino acid substitution, addition, deletion, or combination thereof. In certain aspects, a nucleic acid sequence may be modified to encode a recombinant carboxyl methyltransferase polypeptide variant wherein specific codons of the nucleic acid sequence have been changed to codons that are favored by a particular host and can result in enhanced levels of expression (see, e.g., Haas et al., Curr. Biol. (5:315, 1996; Yang et al., Nucleic Acids Res. 24:4592, 1996). For example, certain codons of the carboxyl methyltransferase polypeptide variants obtained from a library can be optimized, without changing the primary sequence of the polypeptides, for improved expression in Escherichia coli (see, e.g., Figure 4; SEQ ID NOS:91-l 14) or Agrobacterium tumefaciens (see, e.g., Figure 3; SEQ ID NOS:25-48).

Following transformation of a suitable host strain and growth of the host strain to an appropriate cell density, a nucleic acid expression control sequence, if it is an externally regulated promoter, can be induced by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period. Cells are generally harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification. Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze- thaw cycling, sonication, mechanical disruption, or use of cell lysing agents; such methods are well known to those skilled in the art.

A host cell can be a higher eukaryotic cell, such as a mammalian cell, or a lower eukaryotic cell, such as a yeast cell, or the host cell can be a prokaryotic cell, such as a bacterial cell. Representative examples of appropriate host cells according to the present invention include, but need not be limited to, bacterial cells, such as E. coli, A. tumefaciens, Streptomyces, Salmonella tvphimurium; fungal cells, such as yeast; insect cells, such as Drosophila S2 and Spodoptera Sfl>; animal cells, such as MDCK, Hep-2, CHO or COS (e.g., COS-7); human cells such as Jurkat or 293 cells; adenoviruses; plant cells, or any suitable cell already adapted to in vitro propagation or so established de novo.

Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described by Gluzman, Cell 25: 175 (1981), and other cell lines capable of expressing a compatible vector, for example, the C127, 3T3, CHO, HeLa and BHK cell lines. Mammalian expression vectors will comprise an origin of replication, a nucleic acid expression control sequence of the present invention, optionally an enhancer, and also any necessary polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5' flanking non- transcribed sequences. DNA sequences derived from the SV40 splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements.

Introduction of a construct into the host cell can be effected by a variety of methods with which those skilled in the art will be familiar, including calcium phosphate transfection, liposome-mediated transfection, transfection with naked DNA, biolistic particle-mediated transfection, DEAE-Dextran mediated transfection, or electroporation. According to the present disclosure, and as will be appreciated by those having ordinary skill in the art, in certain embodiments at least one nucleic acid expression construct in a host cell may be extrachromosomal, while in certain embodiments at least one nucleic acid expression construct in a host cell may be integrated into a host cell chromosome.

In certain embodiments, this disclosure provides a method for producing one or more carboxyl methyltransferase polypeptide(s) of the present disclosure comprising culturing a host cell containing an expression vector under conditions permitting expression of one or more carboxyl methyltransferase polypeptide(s) and isolating the carboxyl methyltransferase polypeptide(s). Another embodiment comprises a nucleic acid expression construct having an expression control sequence operably-linked to a nucleic acid molecule encoding a carboxyl methyltransferase of the present disclosure. The recombinant carboxyl methyltransferase peptides, polypeptides, fusion proteins or the like may be expressed in mammalian cells, insect cells, plant cells, yeast or other fungi, bacteria, or other cells when part of an appropriate vector capable of replicating in one or more of such cells. Cell-free translation systems may also be employed to produce such carboxyl methyltransferase proteins using RNAs derived from the nucleic acid expression constructs of the present disclosure. Transgenic Herbicide Tolerant Plants

A plant containing a nucleic acid molecule encoding an MT polypeptide of the present disclosure is also provided. Relative to a control plant containing a nucleic acid molecule encoding the selected wild type MT protein, a plant containing the subject nucleic acid molecule is resistant to one or more selected herbicides. Plants, seeds of such plants, and fields of such plants are also provided. Also provided are methods that comprise applying one or more selected herbicides to a transgenic plant in the presence of other plants that do not contain a nucleic acid molecule encoding an altered MT protein of the present disclosure. The application of the selected herbicide controlling the growth of other plants, and allows the preferential growth of the transgenic plant in the presence of the other plants. In certain embodiments, an herbicide may be applied to a transgenic plant with a safener to upregulate MT expression. As used herein, a "safener" is a compound that can used with herbicides to selectively protect plants from herbicide damage without reducing herbicide activity in a target weed species. Safeners are used commercially to improve herbicide selectivity between crop and weed species and can be applied either as a mixture with the herbicide or as a seed-treatment to the crop seed prior to sowing. Exemplary safeners include 1,8-naphthalic anhydride (NA); dichlormid; oxime ether safeners such as cyometrinil, oxabetrinil and fluxofenim; 2,4-disubstituted thiazole carboxylates such as flurazole; benoxacor; cloquintocet-mexyl; fenchlorazole-ethyl; fenchlorim; flurilazole; mefenpyr-diethyl; and MG 191.

The plant may be any plant listed herein. Strategies for expressing exogenous proteins in plants are well known. In plant cells, expression of a protein can be driven from a transgene integrated into a plant chromosome, or cytoplasmically from an episomal or viral nucleic acid. In the case of stably integrated transgenes, it is sometimes desirable to provide sequences capable of driving constitutive or inducible expression of, for example, using viral, e.g., CaMV, or plant derived regulatory sequences. Numerous plant derived regulatory sequences have been described, including sequences which direct expression in a tissue specific manner, e.g., TobRB7, patatin B33, GRP gene promoters, the rbcS-3A promoter, and the like. Alternatively, high level expression can be achieved by transiently expressing an exogenous nucleic acid molecule from a plant viral vector, e.g., TMV, BMV, or the like.

In some embodiments, specific nucleotides of an endogenous wild-type gene of a plant may be substituted by site-specific recombination to provide a modified wild- type gene that encodes a MT protein with the desired activity. In particular

embodiments, the endogenous wild type gene may encode a parental wild-type MT or an ortholog thereof and, as such, the gene may be modified by altering a relatively small number of nucleotide positions. Strategies for performing homologous recombination in plants are known {see, e.g., Cotsaftis et al., Transgenic Res. 14:1, 2005; Ray et al., Trends Plant Sci. 7:435, 2002; Thykjaer et al., Plant Mol. Biol.

55:523, 1997; Darbani, Biotechnol. J. 2:83, 2007).

In certain embodiments, provided is a transgenic plant comprising a nucleic acid molecule encoding a polypeptide of having carboxyl methyltransferase activity on auxin-like herbicides, wherein (a) the nucleic acid molecule comprises a polynucleotide sequence as set forth in SEQ ID NO:22 having at least one mutation that results in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (b) the nucleic acid molecule comprises at least 90% sequence identity with the polynucleotide sequence of (a); (c) the nucleic acid molecule comprises a sequence encoding a polypeptide having carboxyl methyltransferase activity and an amino acid sequence as set forth in SEQ ID NO:70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (d) the nucleic acid molecule encodes a polypeptide comprising an amino acid sequence having carboxyl methyltransferase activity and at least 90% sequence identity with the polypeptide sequence set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; or (e) a nucleic acid molecule that hybridizes under at least high stringency conditions with (i) a full length polynucleotide of any one or more of (a) through (d) or (ii) a full length complementary strand of (i). In certain embodiments, the transgenic plant comprises a nucleic acid molecule further comprising a substitution mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any

combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids, and preferably the encoded polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid. In certain other embodiments, the encoded polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70, and preferably has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid. In certain embodiments, the transgenic plant is resistant to at least two auxin-like herbicides, preferably dicamba and 2,4-D.

In further embodiments, provided is a transgenic plant comprising a nucleic acid molecule encoding a polypeptide having carboxyl methyltransferase activity, wherein (a) the nucleic acid molecule comprises a polynucleotide sequence as set forth in SEQ ID NO:22 having mutations that result in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (b) the nucleic acid molecule comprises a

polynucleotide sequence having at least 90%> identity to the polynucleotide sequence set forth in SEQ ID NO:22 or SEQ ID NO: 86, wherein the polynucleotide having at least 90% identity to SEQ ID NO: 86 does not have a change that alters amino acids encoded at polynucleotide position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof; (c) the nucleic acid molecule comprises a sequence encoding a polypeptide having carboxyl methyltransferase activity on dicamba and

2,4-dichlorophenoxyacetic acid (2,4-D), minimal or no activity on salicylic acid, and an amino acid sequence as set forth in SEQ ID NO:70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; or (d) the nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-D, minimal or no activity on salicylic acid, and an amino acid sequence having at least 90% identity with the polypeptide set forth in SEQ ID NO:70, provided that the 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4 are not altered. In certain embodiments, the transgenic plant comprises a nucleic acid molecule further comprising a substitution mutation at position 469, 470, 471 , 478, 479, 480, 1090, 1091 , 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids, and preferably the encoded polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid. In certain other embodiments, the encoded polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70, and preferably has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid. In certain embodiments, the transgenic plant is resistant to at least two auxin-like herbicides, preferably dicamba and 2,4-D, and preferably is minimally active to inactive on salicylic acid.

In many methods, a constitutive, tissue-specific or inducible promoter may be operably-linked to a polynucleotide of the present disclosure. The vector may be introduced into a variety of plants by means well known in the art such as, for example, direct DNA transfer or Agrobacterium tumefaciens-rnQdiated transformation. Methods for making transgenic monocot and dicot plants, including many of the plants listed herein, are known in the art (see, e.g., Rakoczy-Trojanowska et al., Cell Mol. Biol. Lett. 7:849, 2002; Newell et al, Mol. Biotechnol. 16: 53, 2000; Bates, Methods Mol. Biol. 111 :359, 1999; Birch et al., Annu. Rev. Plant Physiol. Plant Mol. Biol. 48:291, 1997; Dunwell et al., Plant Biotechnol. J. 5:371 , 2005 and Sundar, J. Plant Physiol. 7(55: 1698, 2008).

Nucleic acid molecules encoding carboxy methyltransferase polypeptides active on auxin-like herbicides of the present disclosure may be introduced into a variety of plants, including monocots and dicots, and in particular agriculturally important plant species, including crops such as soybean, wheat, corn (maize), potato, cotton, rice, rape, oilseed rape (including canola, also known as rapeseed), sunflower, alfalfa, clover, sugarcane, and turf; or fruits and vegetables, such as banana, blackberry, blueberry, strawberry, and raspberry, cantaloupe, carrot, cauliflower, coffee, cucumber, eggplant, grapes, honeydew, lettuce, mango, melon, onion, papaya, peas, peppers, pineapple, pumpkin, spinach, squash, sweet corn, tobacco, tomato, tomatillo, watermelon, rosaceous fruits (such as apple, peach, pear, cherry and plum) and vegetable brassicas (such as broccoli, cabbage, cauliflower, Brussels sprouts, and kohlrabi). Other crops, including fruits and vegetables, include barley; rye; millet; sorghum; currant; avocado; citrus fruits such as oranges, lemons, grapefruit and tangerines, artichoke, cherries; nuts such as the walnut and peanut; endive; leek; roots such as arrowroot, beet, cassava, turnip, radish, yam, and sweet potato; and beans. The MT of this disclosure may also be introduced into a woody species, such as pine, poplar and eucalyptus, or mint or other labiates.

In still further embodiments, methods are provide for making a transgenic plant resistant to dicamba and 2,4-D, comprising transforming or transfecting a plant cell with a nucleic acid molecule encoding an MT polypeptide of this disclosure; and contacting the transformed or transfected plant cells with dicamba and 2,4-D in an amount and for a time sufficient to promote unsustainable growth (e.g. , increase in protein synthesis and R A concentration over normal levels, excessive cell division), disrupt growth processes (e.g. , blockage or collapse of vascular transport system), to cause injury symptoms (e.g., stem and petiole twisting (epinasty), leaf malformations (parallel venation, leaf strapping, and cupping), undifferentiated cell masses adventitous root formation on stems, stunted root growth, rolled leaves (onion leafing), fused brace roots, leaning stems, and stalk brittleness), or to kill a plant or plant cells not containing a nucleic acid molecule encoding an MT polypeptide of this disclosure, thereby selecting for transgenic plants resistant to dicamba and 2,4-D.

In certain embodiments, the transgenic plant is a crop plant. Exemplary transgenic crop plants include alfalfa, bean, soybean, wheat, cotton, rapeseed, groundnut, linseed, mustard, castor, niger, cardamom, pepper, chillies, turmeric, ginger, pea, peanut, potato, tomato, squash, papaya, sunflower, sugarcane, sugarbeet, tobacco, maize, sorghum, poplar, or fruit tree.

The following examples describe ways to transform various crop plants.

Rice Transformation: Agrobacterium containing an expression vector of the present disclosure can be used to transform Oryza sativa plants. Mature dry seeds of the rice japonica cultivar Nipponbare are dehusked. Sterilization is carried out by incubating for one minute in 70% ethanol, followed by 30 minutes in 0.2% HgCl₂, followed by a 6 times 15 minutes wash with sterile distilled water. The sterile seeds are then germinated on a medium containing 2,4-D (callus induction medium). After incubation in the dark for four weeks, embryogenic, scutellum-derived calli are excised and propagated on the same medium. After two weeks, the calli are multiplied or propagated by subculture on the same medium for another 2 weeks. Embryogenic callus pieces can be sub-cultured on fresh medium 3 days before co-cultivation (to boost cell division activity).

Agrobacterium strain LBA4404 containing an expression vector of the present disclosure can be used for co-cultivation. Agrobacterium is inoculated on AB medium with the appropriate antibiotics and cultured for 3 days at 28°C. The bacteria are then collected and suspended in liquid co-cultivation medium to a density (OD₆oo) of about 1. The suspension is then transferred to a Petri dish and calli immersed in the suspension for 15 minutes. The callus tissues are then blotted dry on filter paper and transferred to solidified, co-cultivation medium and incubated for 3 days in the dark at 25°C. Co-cultivated calli are grown on 2,4-D-containing medium for 4 weeks in the dark at 28°C in the presence of a selection agent. During this period, rapidly growing resistant callus islands develop. After transfer of this material to a regeneration medium and incubation in the light, the embryogenic potential is released and shoots developed in the next four to five weeks. Shoots are excised from the calli and incubated for 2 to 3 weeks on an auxin-containing medium from which they are transferred to soil.

Hardened shoots are grown under high humidity and short days in a greenhouse.

The primary transformants are transferred from a tissue culture chamber to a greenhouse. After a quantitative PCR analysis to verify copy number of the T-DNA insert, only single copy transgenic plants that exhibit tolerance to the selection agent are kept for harvest of Tl seed. Seeds are then harvested three to five months after transplanting. The method can yield single locus transformants at a rate of over 50% (Aldemita and Hodges, Planta 199:612, 1996, Chan et al, Plant Mol Biol. 22:491, 1993, Hiei et al, Plant J. 6:271, 1994).

Corn Transformation: Transformation of maize (Zea mays) can be performed using a modification of the method described by Ishida et al. (Nature Biotech. 14: 745, 1996). Transformation is genotype-dependent in corn and only specific genotypes are amenable to transformation and regeneration. The inbred line A188 (University of Minnesota) or hybrids with A188 as a parent are good sources of donor material for transformation, but other genotypes can be used successfully as well. Ears are harvested from corn plant approximately 11 days after pollination (DAP) when the length of the immature embryo is about 1 to 1.2 mm. Immature embryos are co- cultivated with Agrobacterium tumefaciens containing the expression vector, and transgenic plants are recovered through organogenesis. Excised embryos are grown on callus induction medium, then maize regeneration medium, containing the selection agent (for example imidazolinone but various selection markers can be used). The plates are incubated in the light at 25°C for 2-3 weeks, or until shoots develop. The green shoots are transferred from each embryo to maize rooting medium and incubated at 25°C for 2-3 weeks, until roots develop. The rooted shoots are transplanted to soil in a greenhouse. Tl seeds are produced from plants that exhibit tolerance to the selection agent and that contain a single copy of the T-DNA insert.

Wheat Transformation: Transformation of wheat can be performed using the method described by Ishida et al. {Nature Biotech. 14: 745, 1996). The cultivar Bobwhite (available from CIMMYT, Mexico) is commonly used in transformation. Immature embryos are co-cultivated with Agrobacterium tumefaciens containing the expression vector, and transgenic plants are recovered through organogenesis. After incubation with Agrobacterium, the embryos are grown in vitro on callus induction medium, and then on regeneration medium containing a selection agent (e.g., imidazolinone). The plates are incubated in the light at 25°C for 2-3 weeks, or until shoots develop. The green shoots are transferred from each embryo to rooting medium and incubated at 25°C for 2-3 weeks, until roots develop. The rooted shoots are transplanted to soil in a greenhouse. Tl seeds are produced from plants that exhibit tolerance to the selection agent and that contain a single copy of the T-DNA insert.

Soybean Transformation: Soybean is transformed according to a modification of the method described in U.S. Pat. No. 5,164,310. Several commercial soybean varieties are amenable to transformation by this method. The cultivar Jack (available from the Illinois Seed foundation) can be used for transformation. Soybean seeds are sterilized for in vitro sowing. The hypocotyl, the radicle and one cotyledon are excised from seven-day old young seedlings. The epicotyl and the remaining cotyledon are further grown to develop axillary nodes. These axillary nodes are excised and incubated with Agrobacterium tumefaciens containing the expression vector. After the co-cultivation treatment, the explants are washed and transferred to selection media. Regenerated shoots are excised and placed on a shoot elongation medium. Shoots no longer than 1 cm are placed on rooting medium until roots develop. The rooted shoots are transplanted to soil in a greenhouse. Tl seeds are produced from plants that exhibit tolerance to the selection agent and that contain a single copy of the T-DNA insert.

Rapeseed/Canola Transformation: Cotyledonary petioles and hypocotyls of 5-6 day old young seedling are used as explants for tissue culture and transformed according to Babic et al. (Plant Cell Rep. 77:183, 1998). The commercial cultivar Westar (Agriculture Canada) is the standard variety used for transformation, but other varieties can also be used. Canola seeds are surface-sterilized for in vitro sowing. The cotyledon petiole explants with the cotyledon attached are excised from the in vitro seedlings, and inoculated with Agrobacterium (containing the expression vector) by dipping the cut end of the petiole explant into the bacterial suspension. The explants are then cultured for 2 days on MSBAP-3 medium containing 3 mg/1 BAP, 3% sucrose, 0.7 Phytagar at 23°C, 16 hr light. After two days of co-cultivation with Agrobacterium, the petiole explants are transferred to MSBAP-3 medium containing 3 mg/1 BAP, cefotaxime, carbenicillin, or timentin (300 mg/1) for 7 days, and then cultured on MSBAP-3 medium with cefotaxime, carbenicillin, or timentin and selection agent until shoot regeneration. When the shoots are 5-10 mm in length, they are cut and transferred to shoot elongation medium (MSBAP-0.5, containing 0.5 mg/1 BAP).

Shoots of about 2 cm in length are transferred to the rooting medium (MS0) for root induction. The rooted shoots are transplanted to soil in a greenhouse. Tl seeds are produced from plants that exhibit tolerance to the selection agent and that contain a single copy of the T-DNA insert.

Alfalfa Transformation: A regenerating clone of alfalfa {Medicago sativa) is transformed using the method of, for example, McKersie et al. {Plant Physiol. 119: 839, 1999). Regeneration and transformation of alfalfa is genotype dependent and therefore a regenerating plant is required. Methods to obtain regenerating plants have been described. For example, these can be selected from the cultivar Rangelander

(Agriculture Canada) or any other commercial alfalfa variety as described by Brown and Atanassov {Plant Cell Tissue Organ Culture 4:111, 1985). Alternatively, the RA3 variety (University of Wisconsin) has been selected for use in tissue culture (Walker et al., Am. J. Bot. 65:654, 1978). Petiole explants are cocultivated with an overnight culture of Agrobacterium tumefaciens C58C 1 pMP90 (McKersie et al., Plant Physiol. ii :839, 1999) or LBA4404 containing the expression vector. The explants are cocultivated for 3 days in the dark on SH induction medium containing 288 mg/L proline, 53 mg/L thioproline, 4.35 g/L K₂S04, and ΙΟΟμΜ acetosyringinone. The explants are washed in half-strength Murashige-Skoog medium (Murashige and Skoog, Physiol. Plant. 75:473, 1962) and plated on the same SH induction medium without acetosyringinone but with a suitable selection agent and suitable antibiotic to inhibit Agrobacterium growth. After several weeks, somatic embryos are transferred to ΒΟΪ2Υ development medium containing no growth regulators, no antibiotics, and 50 g/L sucrose. Somatic embryos are subsequently germinated on half-strength

Murashige-Skoog medium. Rooted seedlings were transplanted into pots and grown in a greenhouse. Tl seeds are produced from plants that exhibit tolerance to the selection agent and that contain a single copy of the T-DNA insert.

Cotton Transformation: Cotton may be transformed using Agrobacterium tumefaciens according to the method, for example, described in U.S. Pat. No.

5,159,135. Cotton seeds are surface sterilized in 3% sodium hypochlorite solution during 20 minutes and washed in distilled water with 500 μg/ml cefotaxime. The seeds are then transferred to SH-medium with 50 μg/ml benomyl for germination.

Hypocotyls of 4 to 6 days old seedlings are removed, cut into 0.5 cm pieces and are placed on 0.8% agar. An Agrobacterium suspension (about 10⁸ cells per ml, diluted from an overnight culture transformed with the gene of interest and suitable selection markers) is used for inoculation of the hypocotyl explants. After 3 days at room temperature and lighting, the tissues are transferred to a solid medium (1.6 g/1 Gelrite) with Murashige and Skoog salts with B5 vitamins (Gamborg et al., Exp. Cell Res. 50: 151, 1968), 0.1 mg/1 2,4-D, 0.1 mg/1 6-furfurylaminopurine and 750 μg/ml MgCL2, and with 50 to 100μg/ml cefotaxime and 400-500 μg/ml carbenicillin to kill residual bacteria. Individual cell lines are isolated after two to three months (with subcultures every four to six weeks) and are further cultivated on selective medium for tissue amplification (30°C, 16 hr photoperiod). Transformed tissues are subsequently further cultivated on non-selective medium during 2 to 3 months to give rise to somatic embryos. Healthy looking embryos of at least 4 mm length are transferred to tubes with SH medium in fine vermiculite, supplemented with 0.1 mg/1 indole acetic acid, 6 furfurylaminopurine and gibberellic acid. The embryos are cultivated at 30°C with a photoperiod of 16 hours, and plantlets at the 2 to 3 leaf stage are transferred to pots with vermiculite and nutrients. The plants are hardened and subsequently moved to a greenhouse for further cultivation.

EXAMPLES

EXAMPLE 1

SPECIFIC ACTIVITY OF REFERENCE METHYLTRANSFERASES

Methyltransferase activity of various wild-type Oryza sativa methyltransferases against plant hormones and synthetic auxin herbicides was measured. Nucleic acid molecules encoding different wild-type Oryza sativa methyltransferases were synthesized with a hexahistidine tag incorporated onto the carboxy-terminal of the methyltransferase coding sequence and cloned into pJexpress 401 (DNA 2.0, Menlo Park, CA). E. coli BL21 were transformed with the methyltransferase expression vector and then induced to express the methyltransferase. The recombinant

hexahistidine tagged methyltransferases were isolated and purified by nickel resin chromatography. Protein concentration was determined using the Bradford assay method (Bradford, Anal. Biochem. 72:248, 1976), and enzyme purity was estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and

Coomassie® brilliant blue staining.

Methyltransferase activity was assayed by direct quantitation of substrate and product by GC/MS. A volume of 5 μΐ purified enzyme (0.5 to 4 mg/ml) was added to 0.5 ml Methyltransferase Assay Buffer (50 mM Tris-HCl pH 7.5; 100 mM KC1; 2.8 mM 2-mercaptoethanol; 0.1 mM 1-heptanol; 1 mM S-adenosyl methionine (SAM)) and the methyltransferase reaction started by adding 5 μΐ of 100 mM substrate (salicylic acid, dicamba or 2,4-D) in ethanol to a 1 mM final concentration. Reactions were carried out at room temperature for 0.5 to 18 hours, and then stopped by adding 50 μΐ concentrated HC1. Substrate and product were extracted with 500 μΐ methylene chloride (CH₂CI₂) containing 0.1 mM 1-octanol. The organic phase was transferred to a fresh tube and dehydrated with 200 mg Na₂S0₄. Following removal of Na₂S0₄, the methylene chloride was evaporated at 65°C, the dried sample was then suspended in 50 μΐ N,0-bis(trimethylsilyl)trifiuoroacetamide (BSTFA) containing 1%

trimethylchlorosilane (TMCS), and then incubated at 65°C for 20 minutes to derivatize the substrate and products.

Substrate and product were analyzed on an Agilent 6890 GC with a 5972 MSD.

A 1 μΐ sample was injected in splitless mode onto an HP-5MS (30 m x 0.25 mm) column (He carrier 1.0 ml min-1; temperature program: 85°C 5 min; ramp to 300°C at 25°C min^"1; 300°C 8.4 min). Carboxylic acid substrate and methyl ester product peaks were identified and quantified by comparison to samples consisting of pure compound dissolved in BSTFA + 1% TMCS. Specific activity was calculated as pmol product produced per second per mg enzyme and results are shown in Table 5.

Table 5. Specific Activity of Reference Methyltransferases

Substrate

MT Clone

Salicylic Acid Dicamba 2,4-D

CB-11 037 43 0 0.003

OS-21 047 0.024 0 0

AM-31 057 4.5 0 0

HVV-71 097 0 0 0.34

CS-62 068 1.4 0 0

OS-72 078 20 0 0

OSI-53 039 0.678 0.620 5.784

RC-63 049 1.6 0 0.87

PT-14 135 1.06 0 0.44 Each of the reference methyltransferases showed different levels of activity against each of salicylic acid, dicamba, and 2,4-D. Interestingly, only OSI-53 showed activity against all three molecules.

EXAMPLE 2

SPECIFIC ACTIVITY OF MUTANT METHYLTRANSFERASES Various different methyltransferase mutants were expressed and isolated to measure methyltransferase activity against plant hormones and synthetic auxin herbicides as compared to their reference or wild-type methyltransferase.

The wild-type and mutant methyltransferases were generated by synthesis of the open reading frame (ORF) including a tag nucleic acid sequence encoding a

"GHHHHHH" (SEQ ID NO:90) at the C-terminus of the ORF, and cloned into pJexpress 401. The following wild-type and mutant methyltransferases were examined:

CB-11 (Clone 037): Clarkia breweri S-adenosyl-L-methionine: salicylic acid carboxyl methyltransferase (SAMT), wild-type

MDVRQVLHMKGGAGENSYAMNSFIQRQVISITKPITEAAITALYSGDTV TTRLAIADLGCSSGPNALFAVTELIKTVEELRKKMGRENSPEYQIFLNDLPGNDF NAIFRSLPIENDVDGVCFINGVPGSFYGRLFPRNTLHFIHSSYSLMWLSQVPIGIE SNKGNIYMANTCPQSVLNAYYKQFQEDHALFLRCRAQEVVPGGRMVLTILGR RSEDRASTECCLIWQLLAMALNQMVSEGLIEEEKMDKFNIPQYTPSPTEVEAEIL KEGSFLIDHIEASEIYWSSCTKDGDGGGSVEEEGYNVARCMRAVAEPLLLDHFG EAIIEDVFHRYKLLIIERMSKEKTKFINVIVSLIRKSD [SEQ ID NO:73]

CB-15m (Clone 116): Clarkia breweri SAMT (Y147S; M150H; F347Y; N349I)

MDVRQVLHMKGGAGENSYAMNSFIQRQVISITKPITEAAITALYSGDTV TTRLAIADLGCSSGPNALFAVTELIKTVEELRKKMGRENSPEYQIFLNDLPGNDF NAIFRSLPIENDVDGVCFINGVPGSFYGRLFPRNTLHFIHSSSSLHWLSQVPIGIES NKGNIYMANTCPQSVLNAYYKQFQEDHALFLRCRAQEVVPGGRMVLTILGRR SEDRASTECCLIWQLLAMALNQMVSEGLIEEEKMDKFNIPQYTPSPTEVEAEIL KEGSFLIDHIEASEIYWSSCTKDGDGGGSVEEEGYNVARCMRAVAEPLLLDHFG EAIIEDVFHRYKLLIIERMSKEKTKYIIVIVSLIRKSD [SEQ ID NO:74]

HVV-71 (Clone 097): Hordeum vulgar e subsp. Vulgare predicted MT, wild-type

MASSLLHCSDKLPFMDVETILHMKEGLDETSYAQNSSLQKRGMDTLKS LIINSATDVYISQMPERFTVADLGCSSGPNALCLVEDIIGGIGKVCCRSSQPPPEFS VLLNDLPTNDFNTIFFSLPEFTHRLKS AAKSDEWGRPMVFLSGVPGSFYGRLFPR TSVHFICSCSSLHWLSQVPPGLFDEAKTPINKGKMYISSTSPPAVSIAYRRQFQR DFSLFLKSRAAEVFPGGRMVLAMLGRQTDECVDRRTTFLWELLSESFAALVSQ GLVEQDKVDAYNVPFYAPSLQEIEVEVRLEGSFSLDYVQTYEINLSSSGDAKED GRTVSMAIRAIQESMLSHHFGPDIVDALFHKYTQLVTESMEREEVKSVQIGVVL TRL [SEQ ID NO:75]

HVV-55m (Clone 156): Hordeum vulgare subsp. Vulgare MT (Q371I)

MASSLLHCSDKLPFMDVETILHMKEGLDETSYAQNSSLQKRGMDTLKS LIINSATDVYISQMPERFTVADLGCSSGPNALCLVEDIIGGIGKVCCRSSQPPPEFS VLLNDLPTNDFNTIFFSLPEFTHRLKS AAKSDEWGRPMVFLSGVPGSFYGRLFPR TSVHFICSCSSLHWLSQVPPGLFDEAKTPINKGKMYISSTSPPAVSIAYRRQFQR DFSLFLKSRAAEVFPGGRMVLAMLGRQTDECVDRRTTFLWELLSESFAALVSQ GLVEQDKVDAYNVPFYAPSLQEIEVEVRLEGSFSLDYVQTYEINLSSSGDAKED GRTVSMAIRAIQESMLSHHFGPDIVDALFHKYTQLVTESMEREEVKSVIIGVVL TRL [SEQ ID NO:76] VV- 12 (Clone 018): Vitis vinifera unnamed MT, wild-type

MVAINFLHVNAGNGEISYANNSLAQKKIILKARAFLEEAIRDRFVSAGFP SCVKLAELGCSSGTNALLAISEIIDTIHEMSQRINCESPEFQVFLNDLPETDFNNIF KSLPAFYEGLMKEKGGKLGNCFVTGMPGSFYGRIFPTRSLDFVHSSASVHWLS QVPAGLKNNKGHIYMANTCRPDVLKAYTKQFQRDFTMFLGLRSEEIKPGGRM VITITGRSIEDPSSKDCCDLWELLAKSLLDMLADGLVEEADVDSFNLPMYNPFE GEVKALIEEEGSFNLDKLETFEASWDPYDDSDKTRSGQNVANCIRSATEPMLAT HFGDAIIPDLFARYANRVAEHLSMEKGHHFLVVFSLTK [SEQ ID NO:77]

VV-35m (Clone 136): Vitis vinifera MT (A154S; H349Y; L351I)

MVAINFLHVNAGNGEISYANNSLAQKKIILKARAFLEEAIRDRFVSAGFP SCVKLAELGCSSGTNALLAISEIIDTIHEMSQRINCESPEFQVFLNDLPETDFNNIF KSLPAFYEGLMKEKGGKLGNCFVTGMPGSFYGRIFPTRSLDFVHSSSSVHWLSQ VPAGLKNNKGHIYMANTCRPDVLKAYTKQFQRDFTMFLGLRSEEIKPGGRMVI TITGRSIEDPSSKDCCDLWELLAKSLLDMLADGLVEEADVDSFNLPMYNPFEGE VKALIEEEGSFNLDKLETFEASWDPYDDSDKTRSGQNVANCIRSATEPMLATHF GDAIIPDLFARYANRVAEHLSMEKGHYFIVVFSLTK [SEQ ID NO:78]

VV-52 (Clone 058): Vitis vinifera putative MT, wild-type

MDVEKAFHMTGGVGETSYARNSSLQKKASDVVKHITIETIQQLYLTTTP RSLGIADLGCSSGPNTLSFIKDIFDAVEGTSSQTLLPAPEFRVYLNDLPTNDFNTI FKALPDFYKELRKGSNGRPSIFIAGFPGSFYGRLFPDNCLHFIYSSYGLHWLSQV PPALYDEQGRSINKGNIYISKSSPPSVSELYLRQFQEDFALFLRSRSEELIEGGRM VLILLGRRGPDHADRGNTFFWELLSRSLAILVSWGEVEEEKLHSYAVNFYAPTK EEIEEEVRREGSFELDRVEMFEIEKDGADDMSYGTQVARTVRAIQESMISLHFG EGIADSLFENYGRLVDEEMAKEDIRPITFLLVLRKSMI [SEQ ID NO:79]

VV-65m (Clone 166): Vitis vinifera MT (Y152S; T352I)

MDVEKAFHMTGGVGETSYARNSSLQKKASDVVKHITIETIQQLYLTTTP RSLGIADLGCSSGPNTLSFIKDIFDAVEGTSSQTLLPAPEFRVYLNDLPTNDFNTI FKALPDFYKELRKGSNGRPSIFIAGFPGSFYGRLFPDNCLHFIYSSSGLHWLSQVP PALYDEQGRSINKGNIYISKSSPPSVSELYLRQFQEDFALFLRSRSEELIEGGRMV LILLGRRGPDHADRGNTFFWELLSRSLAILVSWGEVEEEKLHSYAVNFYAPTKE EIEEEVRREGSFELDRVEMFEIEKDGADDMSYGTQVARTVRAIQESMISLHFGE GIADSLFENYGRLVDEEMAKEDIRPIIFLLVLRKSMI [SEQ ID NO: 80] OSI-53 (Clone 039): Oryza sativa subsp. Indica putative MT, wild-type

MKIERDFHMMKGDDEFSYAENSRIQKRAVLAAKPIVEKAVREVCIDLHP QLMVIADLGCSFGANTLLFVSEAITTICEDHNNTIKESPMEIQFFLNDLPGNDFN HIFQSLEQFEQSTTHDCACKGLQPPAHFVAGLPGSFYSRLFPSNSVHLFHSSMSV MWLSQVPEHLDGSINEGNIHIGATTPPSVAKLYQNQFEKDFSQFLQMRCMEIVP GGRMVLTVAGRK KDVFHAGGTTTLFELLSQGLRTLVAEGRVAKEKLDSFNIP FYCPSADELKQLVQQCELLDISDIQLLEIDGNAMDDSEQAEGISATHTAGESMS ASLRAAMESLIASHFGEGILEDLFTVFARNFTSYIESDVEKSGVTVITLYLQAKH

[SEQ ID NO:81]

OSI-25m (Clone 126): Oryza sativa subsp. Indica MT (M157S, M160H, V364I)

MKIERDFHMMKGDDEFSYAENSRIQKRAVLAAKPIVEKAVREVCIDLHP QLMVIADLGCSFGANTLLFVSEAITTICEDHNNTIKESPMEIQFFLNDLPGNDFN HIFQSLEQFEQSTTHDCACKGLQPPAHFVAGLPGSFYSRLFPSNSVHLFHSSSSV HWLSQVPEHLDGSINEGNIHIGATTPPSVAKLYQNQFEKDFSQFLQMRCMEIVP GGRMVLTVAGRK KDVFHAGGTTTLFELLSQGLRTLVAEGRVAKEKLDSFNIP FYCPSADELKQLVQQCELLDISDIQLLEIDGNAMDDSEQAEGISATHTAGESMS ASLRAAMESLIASHFGEGILEDLFTVFARNFTSYIESDVEKSGITVITLYLQAKH

[SEQ ID NO:82]

OSI-25m (Clone 126) with His tag: Oryza sativa subsp. Indica MT (M157S, M160H, V364I)

MKIERDFHMMKGDDEFSYAENSRIQKRAVLAAKPIVEKAVREVCIDLHP QLMVIADLGCSFGANTLLFVSEAITTICEDHNNTIKESPMEIQFFLNDLPGNDFN HIFQSLEQFEQSTTHDCACKGLQPPAHFVAGLPGSFYSRLFPSNSVHLFHSSSSV HWLSQVPEHLDGSINEGNIHIGATTPPSVAKLYQNQFEKDFSQFLQMRCMEIVP GGRMVLTVAGRK KDVFHAGGTTTLFELLSQGLRTLVAEGRVAKEKLDSFNIP FYCPSADELKQLVQQCELLDISDIQLLEIDGNAMDDSEQAEGISATHTAGESMS ASLRAAMESLIASHFGEGILEDLFTVFARNFTSYIESDVEKSGITVITLYLQAKHG HHHHHH [SEQ ID NO:85]

Nucleic Acid Molecule that encodes OSI-25m (Clone 126) with His tag

ATGAAGATCGAGCGCGATTTCCACATGATGAAAGGGGACGATGAGT TCAGTTATGCTGAGAATTCAAGGATTCAAAAAAGAGCTGTTCTTGCTGCCA AACCAATAGTTGAGAAAGCTGTACGGGAAGTGTGCATAGATCTTCATCCTC AATTAATGGTCATTGCTGACCTTGGTTGCTCCTTCGGAGCAAACACACTTCT CTTCGTCTCTGAGGCGATCACCACAATATGTGAGGACCATAACAACACTAT CAAGGAGAGCCCCATGGAGATCCAGTTCTTCCTCAATGATCTACCTGGCAA TGACTTCAACCACATCTTCCAATCACTAGAGCAGTTCGAGCAGTCGACAAC ACATGATTGCGCTTGCAAAGGGTTACAACCTCCCGCGCACTTTGTCGCAGGT CTGCCGGGTTCCTTCTACAGTAGACTCTTCCCTTCCAATAGCGTCCATCTCTT CCATTCCTCATCGAGCGTCCACTGGCTCTCTCAGGTTCCTGAGCATCTTGAT GGCAGCATAAACGAGGGGAACATTCACATAGGAGCGACTACACCACCATC GGTGGCAAAGCTCTACCAAAATCAGTTTGAGAAGGACTTCTCACAGTTCCT CCAAATGAGATGCATGGAGATTGTGCCCGGAGGCCGGATGGTCCTGACGGT TGCTGGGAGGAAGAACAAAGATGTGTTCCATGCAGGAGGGACAACCACCTT ATTCGAGTTGCTGTCACAGGGGCTACGCACTCTTGTTGCTGAGGGTCGTGTT GCCAAGGAGAAGCTGGACTCTTTCAACATACCATTCTACTGCCCTTCAGCTG ACGAGCTGAAGCAGCTGGTGCAGC AGTGCGAGCTACTTGAC ATAAGTGAC A TCCAACTCTTAGAGATAGATGGGAACGCCATGGATGACTCAGAGCAAGCAG AGGGCATTTCAGCCACTCACACTGCGGGAGAGAGCATGTCTGCAAGCCTAA GGGCGGCAATGGAGTCCCTGATTGCGAGCCATTTTGGGGAGGGCATACTTG AGGATCTCTTCACGGTGTTTGCACGTAATTTCACAAGTTATATTGAGAGTGA TGTTGAGAAGAGCGGCATCACGGTC ATC ACACTGTACTTGCAGGC AAAACA CTAG [SEQ ID NO:86]

Wild-type and mutant methyltransferases were produced and activities measured as described in Example 1. Specific activity in pmol s^"1 mg^"1 are summarized in Table 6.

Specific Activity of Mutant Methytransferases

Mutant CB-15m became a broader spectrum enzyme as compared to wild-type CB-11 - wild-type CB-11 could only modify 2,4-D, while CB-15m could modify 2,4- D, dicamba, and salicylic acid. In contrast, mutant OSI-25m showed an increased level of specificity - wild-type OSI-53 could modify 2,4-D, dicamba and salicylic acid, while mutant OSI-25m could only modify dicamba.

The various embodiments described herein can be combined to provide further embodiments. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, including but not limited to U.S. Patent Application No. 61/736,957, are incorporated herein by reference, in their entirety. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications to provide yet further embodiments.

These and other changes can be made to the embodiments in light of the above- detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.

Claims

CLAIMS What is claimed is:

1. An isolated nucleic acid molecule encoding a polypeptide having carboxyl methyltransferase activity on auxin-like herbicides, wherein:

(a) the nucleic acid molecule comprises a polynucleotide sequence as set forth in SEQ ID NO:22 having at least one mutation that results in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4;

(b) the nucleic acid molecule comprises at least 90% sequence identity with the polynucleotide sequence of (a);

(c) the nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity and an amino acid sequence as set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4;

(d) the nucleic acid molecule encodes a polypeptide comprising an amino acid sequence having carboxyl methyltransferase activity and at least 90% sequence identity with the polypeptide sequence set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; or

(e) a nucleic acid molecule that hybridizes under at least high stringency conditions with (i) a full length polynucleotide of any one or more of (a) through (d) or (ii) a full length complementary strand of (i).

2. The isolated nucleic acid molecule of claim 1 wherein the nucleic acid molecule encoding the carboxyl methyltransferase polypeptide is from Oryza sativa subspecies Indica, Oryza sativa subspecies Japonica, or Oryza sativa subspecies Javanica.

3. The isolated nucleic acid molecule of claim 1 or 2 wherein the encoded polypeptide has carboxyl methyltransferase activity on synthetic auxin- like herbicides.

4. The isolated nucleic acid molecule of any one of claims 1-3 wherein the encoded polypeptide has minimal or no carboxyl methyltransferase activity on natural plant hormones.

5. The isolated nucleic acid molecule of any one of the preceding claims wherein the encoded polypeptide has carboxyl methyltransferase activity on synthetic auxin-like herbicides and minimal or no carboxyl methyltransferase activity on natural plant hormones.

6. The isolated nucleic acid molecule of any one of the preceding claims wherein the encoded polypeptide has carboxyl methyltransferase activity on at least two synthetic auxin- like herbicides.

7. The isolated nucleic acid molecule of any one of the preceding claims wherein the encoded polypeptide has carboxyl methyltransferase activity on two, three, four, or five synthetic auxin-like herbicides.

8. The isolated nucleic acid molecule of any one of the preceding claims wherein the encoded polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D).

9. The isolated nucleic acid molecule of any one of the preceding claims wherein the encoded polypeptide has minimal or no activity on salicylic acid, benzoic acid, indole-3 -acetic acid, or any combination thereof.

10. The isolated nucleic acid molecule of any one of claims 1-8 wherein the encoded polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid, benzoic acid, indole-3 -acetic acid, or any combination thereof.

11. The isolated nucleic acid molecule of any one of the preceding claims wherein the nucleic acid molecule further comprises a substitution mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids.

12. The isolated nucleic acid molecule of claim 1 1 wherein the further mutated nucleic acid molecule encodes a polypeptide having carboxyl

methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid.

13. The isolated nucleic acid molecule of any one of claims 1-10 wherein the encoded polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70.

14. The isolated nucleic acid molecule of claim 13 wherein the further mutated polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid.

15. A vector comprising a nucleic acid molecule encoding a polypeptide of any one of claims 1-14.

16. The vector of claim 15 wherein the encoded polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D), and minimal or no activity on salicylic acid, benzoic acid, indole-3 -acetic acid, or any combination thereof.

17. The vector of claim 15 or 16 wherein the nucleic acid molecule further comprises a substitution mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids.

18. The vector of claim 17 wherein the further mutated nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity on 2,4-D and dicamba, and minimal or no activity on salicylic acid.

19. The vector of claim 15 or 16 wherein the encoded polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO: 70.

20. The vector of claim 19 wherein the further mutated polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid.

21. The vector of any one of claims 15-20 wherein the vector is an expression vector.

22. A recombinant host cell comprising a nucleic acid molecule encoding a polypeptide of any one of claims 1-14.

23. The recombinant host cell of claim 22 wherein the nucleic acid molecule encoding a polypeptide of of any one of claims 1-14 is contained in an expression vector.

24. The recombinant host cell of claim 22 wherein the host cell is a plant cell.

25. A transgenic plant comprising a nucleic acid molecule encoding a polypeptide of any one of claims 1-14, wherein the transgenic plant is resistant to at least two auxin-like herbicides.

26. The transgenic plant of claim 25 wherein the transgenic plant is resistant to dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D).

27. The transgenic plant of claim 26 wherein the encoded polypeptide having carboxyl methyltransferase activity is minimally active to inactive on salicylic acid.

28. The transgenic plant of any one of claims 25-27 wherein the nucleic acid molecule further comprises a substitution mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids.

29. The transgenic plant of claim 28 wherein the further mutated nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid.

30. The transgenic plant of any one of claims 25-27 wherein the encoded polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70.

31. The transgenic plant of claim 30 wherein the further mutated polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-D, and minimal or no activity on salicylic acid.

32. The transgenic plant of any one of claims 25-31 wherein the plant is a crop plant.

33. The transgenic plant of claim 32 wherein the crop plant is alfalfa, bean, soybean, wheat, cotton, rapeseed, groundnut, linseed, mustard, castor, niger, cardamom, pepper, chillies, turmeric, ginger, pea, peanut, potato, tomato, squash, papaya, sunflower, sugarcane, sugarbeet, tobacco, maize, sorghum, poplar, and fruit tree.

34. A method for making a transgenic plant resistant to dicamba and 2,4-D, comprising transforming or transfecting a plant cell with a nucleic acid molecule encoding a polypeptide of any one of claims 1-14; and contacting the transformed or transfected plant cells with an amount of dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D) and for a time sufficient to slow growth, inhibit growth or kill plant cells not containing a nucleic acid molecule encoding a polypeptide of any one of claims 1-14, thereby selecting for transgenic plants resistant to dicamba and 2,4-D.

35. An isolated nucleic acid molecule encoding a polypeptide having carboxyl methyltransferase activity, wherein:

(a) the nucleic acid molecule comprises a polynucleotide sequence as set forth in SEQ ID NO:22 having mutations that result in 1 to about 20 amino acid substitutions in an encoded polypeptide at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4;

(b) the nucleic acid molecule comprises a polynucleotide sequence having at least 90% identity to a polynucleotide sequence of SEQ ID NO:22, 84 or 86, wherein the polynucleotide having at least 90% identity to SEQ ID NO: 86 does not have a change that alters amino acids encoded at polynucleotide position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof;

(c) the nucleic acid molecule comprises a sequence encoding a polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D), minimal or no activity on salicylic acid, and an amino acid sequence as set forth in SEQ ID NO:70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4; (d) the nucleic acid molecule encodes a polypeptide having carboxyl methyltransferase activity on dicamba and 2,4-D, minimal or no activity on salicylic acid, and an amino acid sequence having at least 90% identity with the polypeptide set forth in SEQ ID NO:70, provided that the 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4 are not altered.

36. The isolated nucleic acid molecule of claim 35 wherein the nucleic acid molecule encoding the carboxyl methyltransferase polypeptide is from Oryza sativa subspecies Indica, Oryza sativa subspecies Japonica, or Oryza sativa subspecies Javanica.

37. The isolated nucleic acid molecule of claim 35 or 36 wherein the encoded polypeptide has carboxyl methyltransferase activity on three, four, or five synthetic auxin- like herbicides.

38. The isolated nucleic acid molecule of any one of claims 35-37 wherein the nucleic acid molecule further comprises a substitution mutation at position 469, 470, 471, 478, 479, 480, 1090, 1091, 1092, or any combination thereof of the polynucleotide sequence set forth in SEQ ID NO:22 provided that the mutation or mutations result in a substitution mutation of the encoded amino acid or amino acids.

39. The isolated nucleic acid molecule of claim 35 wherein the encoded polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70.

40. A recombinant polypeptide comprising an amino acid sequence having carboxyl methyltransferase activity on synthetic auxins and at least 90% identity with the polypeptide set forth in SEQ ID NO:70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4.

41. The recombinant polypeptide of claim 40 wherein the amino acid sequence is as set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4.

42. The recombinant polypeptide of claim 40 wherein the polypeptide has carboxyl methyltransferase activity on dicamba and 2,4-D, minimal or no activity on salicylic acid, and an amino acid sequence as set forth in SEQ ID NO: 70 comprising from 1 to about 20 mutations at positions, paired positions, or combinations thereof selected from those listed in Tables 1-4.

43. The recombinant polypeptide of any one of claims 40-42 wherein the polypeptide further comprises a substitution mutation at position M157, M160, V364, or any combination thereof of the sequence set forth in SEQ ID NO:70.