CZ20003397A3 - Varianta serinové proteázy; prostředek pro osobní hygienu, čistící prostředek, mutovaný gen - Google Patents
Varianta serinové proteázy; prostředek pro osobní hygienu, čistící prostředek, mutovaný gen Download PDFInfo
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- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
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- Enzymes And Modification Thereof (AREA)
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Abstract
Řešení se týká variant serinové proteázy a prostředků,
obsahujících varianty, které mají sníženou imunogenicitu ve
srovnání sjejich odpovídajícími standardními serinovými
proteázami. Zvláště se týká variant, které mají pozměněnou
aminokyselinovou sekvenci oproti standardní
aminokyselinové sekvenci, přičemž pozměněná
aminokyselinová sekvence obsahuje substituci na jedné nebo
více specificky určených pozicích, odpovídajících subtilizinu
BPN'. Rovněž jsou popsány mutované geny, které tyto
varianty kódují, čistící prostředky a prostředky pro osobní
hygienu, které tyto varianty obsahují. .
Description
Varianta serinové proteázy, mutovaný gen.
Λ * - ······ .!..... ......
prostředek pro osobní hygienu, čistící prostředek,
Oblast techniky ť Předkládaný vynález se týká variant serinové proteázy a prostředků, obsahujících varianty, které mají sníženou imunogenicitu ve srovnání s jejich í ' ....... - .
odpovídajícími standardními serinovými proteázami.
Ά ' í ' Dosavadní stav techniky
Enzymy tvoří největší třídu přirozeně se vyskytujících proteinů. Jedna třída enzymů zahrnuje proteázy, které katalyzují hydro,ýzu jiných proteinů. Tato schopnost hydrolyzovat proteiny byla využita začleněním přirozeně se vyskytujících nebo upravených proteáz do čistících prostředků, zvláště těch, které jsou vhodné pro použití v prádelnách.
V oboru čistění se z těchto proteáz nejčastěji používají serinové proteázy. Většina serinových proteáz je produkována bakteriálními organizmy a některé jsou vytvářeny organizmy jinými, jako jsou houby. Viz Siezen, Roland J. a kok, „Homology Modelling and Protein Engeneering Stratégy of Subtilases, the Family of Subtilizin-Like Serine Proteases“, Protein Engineering, sv. 4, č. 7, str. 719 až 737 (1991). Bohužel účinnost standardních serinových proteáz v jejich přirozeném prostředí se často nepřenáší do nepřirozeného prostředí čistících prostředků. Zvláště charakteristické vlastnosti proteáz, jako jsou například tepelná stabilita, pH stabilita, stabilita vůči oxidaci a substrátová specificita často nejsou optimalizované pro použití mimo přirozené prostředí enzymu.
Bylo použito několik přístupů jak změnit standardní aminokyselinovou sekvenci serinových proteáz s cílem zvýšit účinnost proteázy v nepřirozeném prostředí při praní. Tyto přístupy zahrnují genetické přebudování proteáz tak, aby se zvýšila tepelná stabilita a zlepšila stabilita vůči oxidaci ve zcela odlišných podmínkách.
Protože však takové geneticky upravené proteázy jsou pro savce cizí, jsou pro ně potenciálními antigeny. Jakožto antigeny, tyto proteázy způsobují imunologické a alergické odpovědi (zde společně popisované jako imunologické odpovědi) u savců.
ί * 3 3 '30 3
3 3
3 3
5 S 3 3
3 0 3
3 0 3
3 ο 3
3 Ο 3
2 3 3
3i 3 ί i ϊ 3 3 0 '3 Í -S
- 3 3
3 · ί » Ο < ·
Skutečně byla přecitlivělost na serinové proteázy pozorována v prostředích, kde jsou. lidé proteázám pravidelně vystaveni. Taková prostředí jsou ve výrobních zařízeních, kde jsou zaměstnanci vystaveni proteázám prostřednictvím takových nosičů, jako je prach a aerosoly. Aerosoly mohou mít za následek zanesení proteázy do plic, což je takový způsob vystavení proteáze, který vyvolává nejnebezpečnější odpověď. Přecitlivělost na proteázu může také nastat na trhu, kde opakované používání proteázy obsahujících výrobků zákazníkem, může způsobit alergickou reakci. ; Kromě toho, zatímco genetické /úpravy byly nejvýznamnější při pokračujícím hledání ještě účinnějších proteáz použitelných pro praní, geneticky upravené proteázy byty minimálně použity v prostředcích,určených pro osobní hygienu a slabé saponáty. Primárním důvodem nepřítomnosti upravených proteáz ve výrobcích, jako jsou například mýdla, gely, koupelnové prostředky a šampóny, je výše zmíněný problém lidské přecitlivělosti, vedoucí k nežádoucím imunologickým odpovědím. Bylo by tedy vysoce výhodné poskytnout prostředek pro osobní hygienu, který využije čistící schopnosti upravených proteáz a přitom bude minimálně vyvolávat imunologické odpovědi.
Jeden přístup, jak zmírnit imunologickou aktivitu proteázy, je přebudovat jeden nebo více jejích epitopů. Epitopy jsou takové aminokyselinové oblasti antigenů, které vyvolávají imunologickou odpověď vazbou protilátek nebo prezentací zpracovaných antigenů T buňkám prostřednictvím hlavního histokompatibilitního komplexu (MHC). Změny v epitopech mohou ovlivnit jejich účinnost jako antigenů. Viz Walsh, B. J. a M. E. H. Howden, Λ Method for the Detection of IgE Binding Sequences of Allergens Based on a Modification of Epitope Mapping“, Journal of Immunological Methods, sv. 121, str. 275 až 280 (1989).
Nynější vynálezci zjistili, že ty serinové proteázy, obecně známé jako subtiliziny, včetně subtilizinu BPN', mají význačnou epitopovou oblast na aminokyselinových pozicích 70 až 84 odpovídající BPN'. Nynější vynálezci zde takové subtiliziny geneticky přebudovali, aby se zmírnily imunologické vlastnosti, připisované této epitopové oblasti.
Přitom tito vynálezci objevili subtiliziny, které vyvolávají sníženou imunologickou odpověď a přitom si podržují svou aktivitu jako účinná čistící proteáza. Proto jsou předkládané proteázy vhodné pro použití v několika typech prostředků, jako jsou mimo jiné prostředky na praní, mytí nádobí, znečistěné povrchy, prostředky péče o kůži, • ·
prostředky péče o vlasy, zkrášlovací prostředky, prostředky ústní hygieny a prostředky pro ošetřování kontaktních čoček.
Podstata vynálezu
Předkládaný vynález se týká variant serinových proteáz, které mají imunogenicitu sníženou, vzhledem k odpovídajícím setinovým proteázám standardním. Zvláště se předkládaný vynález týká variant, které mají pozměněnou aminokyselinovou sekvenci oproti standardní aminokyselinové sekvenci, přičemž pozměněná aminokyselinová sekvence obsahuje substituce na jedné nebo více z pozic 70 až 84, odpovídajících subtilizinu BPN'. Vynález se. dále týká mutovaných genů, které tyto-----varianty kódují, a čistících prostředků a prostředků pro osobní hygienu, které tyto varianty obsahují.
Podstatné složky předkládaného vynálezu jsou popsány zde dále. Také jsou zahrnuty popisy různých možných a výhodných složek, užitečných při provedení předkládaného vynálezu. / ?
Předkládaný vynález může obsahovat, sestávat z, nebo sestávat v podstatě z jakýchkoli požadovaných nebo volitelných složek a/nebo omezení zde popsaných.
Všechna procenta a poměry jsou počítána jako hmotnostní procenta, pokud není stanoveno jinak. Všechna procenta jsou vypočítána na základě celkového složení, pokud není stanoveno jinak.
Všechny složky nebo jejich úrovně se vztahují k aktivní úrovni dané složky nebo prostředku, a nejsou do nich započítávány nečistoty, například zbytky roztoků nebo vedlejších produktů, které mohou být přítomny v komerčně dostupných zdrojích.
Všechny dokumenty, na které je zde odkazováno, včetně všech patentů, patentových přihlášek a tištěných publikací, jsou zahrnuty jako odkaz ve své úplnosti.
Pro popis aminokyselin zde budou používány zkratky. Tabulka I podává seznam všech zde používaných zkratek:
• · ·« • β β β · «6 · • ·. * '· · · · β— — w ·· · · · · · · Λ · · ·······
Α ···· ··· ··· ·· ·· ··
Tabulka I
| Aminokyselina | TříDísmenová zkratka | JednoDísmenová zkratka |
| Alanin | Ala | A |
| Arginin | Arg | R |
| Asparagin | Asn | N |
| Kysl. asparagová | Ásp | D |
| Cystein | Cys | C |
| Glutamin | Gin | Q |
| Kysl. glutamová | Glu | E |
| Glycin | Gly | G |
| Histidin , | His | H |
| Izoleucin | lle | 1 |
| Leucin | Leu | L |
| Lyzin | Lys | K |
| Metionin | Met | M |
| Fenylalanin | Phe | F |
| Prolin | Pro | P |
| Šeřin | Ser ’ | s |
| Treonin | Thr | T |
| Tryptofan | Trp | W |
| Ty rozin | Tyr | Y |
| Valin | Val | V |
Definice
Zde používaný termín „mutace“ označuje změnu v genových sekvencích a v aminokyselinových sekvencích, produkovaných těmito genovými sekvencemi. Mutace mohou být delece, substituce nebo adice aminokyselinových zbytků v standardní sekvenci proteinu.
Zde používaný termín „standardní“ označuje protein, zde specificky proteázu, produkovanou nemutovaným organizmem.
Zde používaný termín „varianta“ označuje protein, zde specificky proteázu, která má aminokyselinovou sekvenci, lišící se od aminokyselinové sekvence standardní proteázy.
Jak je zde uvedeno, zatímco varianty v předkládaném vynálezu nejsou omezeny pouze na varianty subtiiizinu BPN', veškeré číslování aminokyselin je provedeno s ohledem na aminokyselinovou sekvenci subtilizinu BPN', která je uvedena v SEQ ID
NO: 1. Aminokyselinová sekvence subtilizinu BPN' je dále popsána v práci Wells, J.A.,
E. Ferrari, D.J. Henner, D.A. Estell a E.Y. Chen, Nucleic Acids Research, sv. II, str.
7911 až 7925 (1983), která je zde zahrnuta jako odkaz.
Varianty předkládaného vynálezu.
Předkladatelé vynálezu objevili epitopovou oblast v serinových proteázách, která odpovídá pozicím 70 až 84 v subtilizinu BPN'. Předkladatelé vynálezu dále objevili, že jedna nebo více aminokyselinových substitucí v aminokyselinové sekvenci standardní serinové proteázy poskytuje varianty, které vyvolávají sníženou alergickou a/nebo imunitní odpověď ve srovnání s odpovídající standardní serinovou proteázou.
Varianty zde mohou být označeny uvedením pozic odstraněných aminokyselin, které charakterizují variantu. Substituce jsou zde označeny uvedením standardního aminokyselinového zbytku, po němž následuje číslo pozice a potom následuje substituovaný aminokyselinový zbytek, kterým byla substituce provedena. Tam, kde substituujícím aminokyselinovým zbytkem může být kterákoli přírodní aminokyselina, je uváděn symbol Mnohočetné substituce obsažené ve variantách jsou odděleny symbolem Pro ilustraci, substituce glycinu valinem v pozici 70 je označena buď Gly70Val nebo G70V. Příklad varianty, která má substituce na obou pozicích 70 a 72, může být označován jako Gly70Val + Val72Ala nebo G70V + V72A.
Varianty v předloženém vynálezu jsou varianty serinových proteáz. Zde používaný termín „serinová proteáza“ znamená proteázu, která má alespoň 50% a výhodně 80% aminokyselinovou sekvenční shodu se sekvencemi jedné nebo více serinových proteáz subtilizinového typu. Diskuze týkající se subtilizinového typu serinových proteáz a jejich homologií lze nalézt v Siezen a kol., „Homology Modelling and Protein Engineering Stratégy of Subtilases, the Family of Subtilisin-Like Serine Proteases“, Protein Engineering, sv. 4, č. 7, str. 719 až 737 (1991). Výhodné serinové proteázy pro provádění mutací zahrnují subtilizin BPN', subtilizin Carisberg, subtilizin DY, subtilizin 309, proteinázu Ka thermitázu. Nejvýhodnější serinová proteáza pro provádění mutací je subtilizin BPN'.
Varianty představené v předloženém vynálezu jsou varianty serinových proteáz, které mají pozměněnou standardní aminokyselinovou sekvenci, kde pozměněná aminokyselinová sekvence obsahuje substituci na jedné nebo více z pozic 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83 a 84 (70 až 84), odpovídajících BPN'. Je θ φφφφφφφ φ φ φ φ φ · · φ φ výhodnější, když pozměněná aminokyselinová sekvence obsahuje substituci na dvou nebo více z těchto pozic. Substituce na těchto pozicích jsou vytvořeny zaměněním standardního aminokyselinového zbytku jiným přirozeným aminokyselinovým zbytkem, jedním z těch, které jsou uvedeny v tabulce 1.
Přesněji, když varianta má pozměněnou standardní aminokyselinovou sekvenci, obsahující substituci na jedné z pozic, odpovídajících pozicím 70 až 84 BPN':
(a) pokud substituce nastane na pozici 70, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;
(b) pokud substituce nastane na pozici 71, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Cys, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Trp, Tyr a Val;
(c) pokud substituce nastane na pozici 72, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp a Tyr;
(d) pokud substituce nastane na pozici 73, substituující aminokyselina pochází ze skupiny, obsahující Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, Ile, Lys, Met, Pro, Ser, Thr, Trp, Tyr a Val;
(e) pokud substituce nastane na pozici 74, substituující aminokyselina pochází ze skupiny, obsahující Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;
(f) pokud substituce nastane na pozici 75, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, Ile, Lys, Met, Gin, Ser, Thr, Trp, Tyr a Val;
(g) pokud substituce nastane na pozici 76, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Cys, Ile, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;
(h) pokud substituce nastane na pozici 77, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Cys, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;
(i) pokud substituce nastane na pozici 78, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Cys, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Thr, Trp, Tyr a Val;
······ · ·· · · ·· • · · ···· ···· • · ·· · β - · e β ο 9(j) pokud substituce nastane na pozici 79, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Cys, Gly, Phe, His, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;
(k) pokud substituce nastane na pozici 80, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;
(l) pokud substituce nastane na pozici 81, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp a Tyr, (m) pokud substituce nastane pa pozici 82, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, lle, Lys, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;
(n) pokud substituce nastane na pozici 83, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val; a (o) pokud substituce nastane na pozici 84, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe; His, lle, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp a Tyr.
Když varianta má pozměněnou standardní aminokyselinovou sekvenci, obsahující substituci na dvou nebo více pozicích, odpovídajících pozicím 70 až 84 BPN':
(a) pokud substituce nastane na pozici 70, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Phe, His, lie, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;
(b) pokud substituce nastane na pozici 71, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Ser, Trp, Tyr a Val;
(c) pokud substituce nastane na pozici 72, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp a Tyr;
(d) pokud substituce nastane na pozici 73, substituující aminokyselina pochází ze skupiny, obsahující Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;
| ·· ··!· | • «· | ·· | • · | ||
| • ♦ · | • · · · | • | • | • | • |
| e e ee | • | • | • | • | |
| • | |||||
| • · | • · · | • | • | • | • |
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(e) pokud substituce nastane na pozici 74, substituující aminokyselina pochází ze skupiny, obsahující Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;
(f) pokud substituce nastane na pozici 75, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, ile, Lys, Met, Pro, Ser, Thr, Trp, Tyr a Val;
(g) pokud substituce nastane na pozici 76, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;
(h) pokud substituce nastane na pozici 77, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;
(i) pokud substituce nastane na pozici 78, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Thr, Trp, Tyr a Val;
(j) pokud substituce nastane na pozici 79, substituující aminokyselina pochází ze skupiny, obsahující Aíá> Arg· Asn, Asp/Cys; Gin; Glu, Gly, Pheř His, Lys, Leu, Meť, Pro, Ser, Thr, Trp, Tyr a Val;
(k) pokud substituce nastane na pozici 80, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;
(l) pokud substituce nastane na pozici 81, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp a Tyr;
(m) pokud substituce nastane na pozici 82, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Met, Pro, Ser, Thr, Trp, Tyr a Val;
(n) pokud substituce nastane na pozici 83, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Phe, His, ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val; a (o) pokud substituce nastane na pozici 84, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp a Tyr;
· ·· β · ··< · • · • 4 44 kde není varianta Asn76Asp + Asn77Asp; Asn76Asp + lle79Glu nebo Asn76Asp +
Ser79Asp.
Dokonce ještě výhodněji, varianty předloženého vynálezu obsahuji deleci jedné nebo více z pozic 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83 (73 až 83), dokonce ještě výhodněji jedné nebo více z pozic 75, 76, 77, 78, 79, 80, 81, 82 (75 až 82).
Tabulky 2 až 10 uvedené dále, uvádějí příklady některých výhodných variant, které jsou předmětem tohoto vynálezu. Pokud se týká těchto tabulek, při popisování specifických substitucí je prvně uveden standardní aminokyselinový zbytek a jako druhé je uvedeno číslo odpovídající pozice a jako třetí je uvedena substituující aminokyselina. Tabulky 3 až 7 popisují výhodné varianty, které mají dvě nebo více substitucí. Pro ilustraci, první příklad v tabulce 3 se čte „VAL 81 THR LEU 82 PHE“. Tento příklad představuje variantu Val81 Thr + Leu82Phe.
Za použití podobného značení, tabulky 8 až 13 představují ještě výhodnější varianty, které jsou předmětem tohoto vynálezu.
Tabulka 2
Jednoduché substituční varianty
GLY 83 VAL LEU 82 PHE LEU 82 HIS LEU 82 TYR LEU 82 ALA VAL 81 THR VAL 81 ALA GLY 80 VAL ILE 79 LEU ILE 79 MET ILE 79 THR ILE 79 VAL ILE 79 ALA SER 78 ASN SER 78 THR SER 78 ARG SER 78GLN SER 78 HIS SER 78 LYS SÉR 78 TYR SER 78 ALA ASN 77 ALA , ASN 76 ALA LEU 75 ILE ‘LEU 75 MET LEU 75 VAL LEU 75 ALA ALA 74 VAL ALA 73 VAL VAL 72 ALA THR 71 ALA GLY 70 VAL
Tabulka 3
Dvojité substituční varianty
VAL 81 THR LEU 82 PHE VAL 81 THR LEU 82 HIS VAL 81 THR LEU 82 TYR ILE 79 LEU LEU 82 PHE ILE 79 LEU LEU 82 HIS ILE 79 LEU LEU 82 TYR ILE 79 MET LEU 82 PHE ILE 79 MET LEU 82 HIS ILE 79 MET LEU 82 TYR ILE 79 THR LEU 82 PHE ILE 79 THR LEU 82 HIS ILE 79 THR LEU 82 TYR ILE 79 VAL LEU 82 PHE ILE 79 VAL LEU 82 HIS ILE 79 VAL LEU 82 TYR
ILE 79 LEU VAL 81 THR ILE 79 MET VAL 81 THR ILE 79 THR VAL 81 THR ILE 79 VAL VAL 81 THR SER 78 ASN LEU 82 PHE SER 78 ASN LEU 82 HIS SER 78 ASN LEU 82 TYR SEŘ 78 THR LEU 82 PHE SER 78 THR LEU 82 HIS SER 78 THR LEU 82 TYR SER 78 ARG LEU 82 PHE SER 78 ARG LEU 82 HIS SER 78 ARG LEU. 82 TYR SER 78 ASP LEU 82 PHE SER 78 ASP LEU 82 HIS SER 78 ASP LEU 82 TYR SER 78 GLN LEU 82 PHE SER 78 GLN LEU 82 HIS SER 78 GLN LEU 82 TYR SER 78 HIS LEU 82 PHE SER 78 HIS LEU 82 HIS SER 78 HIS LEU 82 TYR SER 78 LYS LEU 82 PHE SER 78 LYS LEU 82 HIS SER 78 LYS LEU 82 TYR SER 78 TYR LEU 82 PHE SER 78 TYRLEU 82 HIS SER 78 TYR LEU 82 TYR SER 78 ASN VAL 81 THR SER 78 THR VAL 81 THR SER 78 ARG VAL 81 THR SER 78 ASP VAL 81 THR SER 78 GLN VAL 81 THR SER 78 HIS VAL 81 THR SER 78 LYS VAL 81 THR SER 78 TYR VAL 81 THR SER 78 ASN ILE 79 LEU SER 78 ASN ILE 79 MET SER 78 ASN ILE 79 THR SER 78 ASN ILE 79 VAL SER 78 THR ILE 79 LEU SER 78 THR ILE 79 MET SER 78 THR ILE 79 THR SER 78 THR ILE 79 VAL SER 78 ARG ILE 79 LEU SER 78 ARG ILE 79 MET SER 78 ARG ILE 79 THR SER 78 ARG ILE 79 VAL SER 78 ASP ILE 79 LEU SER 78 ASP ILE 79 MÉT SER 78 ASP ILE 79 THR SER 78 ASP ILE 79 VAL SER 78 GLN ILE 79 LEU SER 78 GLN ILE 79 MET SER 78 GLN ILE 79 THR SER 78 GLN ILE 79 VAL
SER 78 HIS ILE 79 LEU SER 78 HIS ILE 79 MET SER 78 HIS ILE 79 THR SER 78 HIS ILE 79 VAL SER 78 LYS ILE 79 LEU SER 78 LYS ILE 79 MET SER 78 LYS ÍLE 79 THR SER 78 LYS ILE 79 VAL SER 78 TYR ILE 79 LEU SER 78 TYR ILE 79 MET SER 78 TYR ILE 79 THR SER 78 TYR ILE 79 VAL ASN 76 HIS LEU 82 PHE ASN 76 HIS LEU 82 HIS ASN 76 HIS LEU 82 TYR ASN 76 HIS VAL 81 THR ASN 76 HIS ILE 79 LEU ASN 76 HIS ILE 79 MET ASN 76 HIS ILE 79 THR ASN 76HIŠILE 79 VAL ASN 76 HIS SER 78 ASN ASN 76 HIS SER 78 THR ASN 76 HIS SER 78 ARG . ASN 76 HIS SER 78 ASP ASN 76 HIS SER 78 GLN ‘ ASN 76 HIS SER 78 HIS ASN 76 HIS SER 78 LYS ASN 76 HIS ŠER 78 TYR . LEU 75 ILE LEU 82 PHE LEU 75 ILE LEU 82 HIS LEU 75 ILE LEU 82 TYR LEU 75 MET LEU 82 PHE LEU 75 MET LEU 82 HIS LEU 75 MET LEU 82 TYR LEU 75 VAL LEU 82 PHE LEU 75 VAL LEU 82 HIS LEU 75 VAL LEU 82 TYR LEU 75 ILE VAL 81 THR LEU 75 MET VAL 81 THR LEU 75 VAL VAL 81 THR LEU 75 ILE ILE 79 LEU LEU 75 ILE ILE 79 MET LEU 75 ILE ILE 79 THR LEU 75 ILE ILE 79 VAL LEU 75 MET ILE 79 LEU LEU 75 MET ILE 79 MET LEU 75 MET ILE 79 THR LEU 75 MET ILE 79 VAL LEU 75 VAL ILE 79 LEU LEU 75 VAL ILE 79 MET LEU 75 VAL ILE 79 THR LEU 75 VAL ILE 79 VAL LEU 75 ILE SER 78 ASN LEU 75 ILE SER 78 THR LEU 75 ILE SER 78 ARG LEU 75 ILE SER 78 ASP
LEU 75 ILE SER 78 GLN LEU 75 ILE SER 78 HIS LEU 75 ILE SER 78 LYS LEU 75 ILE SER 78 TYR LEU 75 MET SER 78 ASN LEU 75 MET SER 78 THR LEU 75 MET SER 78 ARG LEU 75 MET SER 78 ASP LEU 75 MET SER 78 GLN LEU 75 MET SER 78 HIS; LEU 75 MET SER 78 LYS LEU 75 MET SER 78 TYR LEU 75 VAL SER 78 ASN LEU 75 VAL SER 78 THR LEU 75 VAL SER 78 ARG LEU 75 VAL SER 78 ASP LEU 75 VAL SER 78 GLN LEU 75 VAL SER 78 HIS LEU 75 VAL SER 78 LYS LEU 75 VAL SER 78 TYR LEU 75 ILE ASN 76 HIS LEU 75 MET ASN 76 HIS LEU 75 VAL ASN 76 HIS
Tabulka 4
Trojnásobné substituční varianty
ILE 79 LEU VAL 81 THR LEU 82 PHE ILE 79 LEU VAL 81 THR LEU 82 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR ILE 79 MET VAL 81 THR LEU 82 PHE ILE 79 MET VAL 81 THR LEU 82 HIS ILE 79 MET VAL 81 THR LEU 82 TYR ILE 79 THR VAL 81 THR LEU 82 PHE ILE 79 THR VAL 81 THR LEU 82 HIS ILE 79 THR VAL 81THRLEU 82 TYR ILE 79 VAL VAL 81 THR LEU 82 PHE ILE 79 VAL VAL 81 THR LEU 82 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR SER 78 ASN VAL 81 THR LEU 82 PHE SER 78 ASN VAL 81 THR LEU 82 HIS SER 78 ASN VAL 81 THR LEU 82 TYR SER 78 THR VAL 81 THR LEU 82 PHE SER 78 THR VAL 81 THR LEU 82 HIS SER 78 THR VAL 81 THR LEU 82 TYR SER 78 ARG VAL 81 THR LEU 82 PHE SER 78 ARG VAL 81 THR LEU 82 HIS SER 78 ARG VAL 81 THR LEU 82 TYR SER 78 ASP VAL 81 THR LEU 82 PHE SER 78 ASP VAL 81 THR LEU 82 HIS SER 78 ASP VAL 81 THR LEU 82 TYR SER 78 GLN VAL 81 THR LEU 82 PHE SER 78 GLN VAL 81 THR LEU 82 HIS SER 78 GLN VAL 81 THR LEU 82 TYR SER 78 HIS VAL 81 THR LEU 82 PHE
• · ··
SER 78 HIS VAL 81 THR LEU 82 HIS SER 78 HIS VAL 81 THR LEU 82 TYR SER 78 LYS VAL 81 THR LEU 82 PHE SER 78 LYS VAL 81 THR LEU 82 HIS SER 78 LYS VAL 81 THR LEU 82 TYR SER 78 TYR VAL 81 THR LEU 82 PHE SER 78 TYR VAL 81 THR LEU 82 HIS SER 78 TYR VAL 81 THR LEU 82 TYR SER 78 ASN ILE 79 LEU LEU 82 PHE SER 78 ASN ILE 79 LEU LEU 82 HIS SER 78 ASN ILE 79 LEU LEU 82 TYR SER 78 ASN ILE 79 MET LEU 82 PHE SER 78 ASN ILE 79 MET LEU 82 HIS SER 78 ASN ILE 79 MET LEU 82 TYR SER 78 ASN ILE 79 THR LEU 82 PHE SER 78 ASN ILE 79 THR LEU 82 HIS SER 78 ASN ILE 79 THR LEU 82 TYR SER 78 ASN ILE 79 VAL LEU 82 PHE SER 78 ASN ILE 79 VAL LEU 82 HIS SER 78 ASN ILE 79 VÁL LEU 82 TYR SER 78 THR ILE 79 LEU LEU 82 PHE SER 78 THR ILE 79 LEU LEU 82 HIS SER 78 THR ILE 79 LEU LEU 82 TYR SER 78 THR ILE 79 MET LEU 82 PHE SER 78 THR ILE 79 MET LEU 82 HIS SER 78 THR ILE 79 MET LEU 82 TYR SER 78 THR ILE 79 THR LEU 82 PHE SER 78 THR ILE 79 THR LEU 82 HIS SER 78 THR ILE 79 THR LEU 82 TYR SER 78 THR ILE 79 VAL LEU 82 PHE SER 78 THR ILE 79 VAL LEU 82 HIS SER 78 THR ILE 79 VAL LEU 82 TYR SER 78 ARG ILE 79 LEU LEU 82 PHE SER 78 ARG ILE 79 LEU LEU 82 HIS SER 78 ARG ILE 79 LEU LEU 82 TYR SER 78 ARG ILE 79 MET LEU 82 PHE SER 78 ARG ILE 79 MET LEU 82 HIS SER 78 ARG ILE 79 MET LEU 82 TYR SER 78 ARG ILE 79 THR LEU 82 PHE SER 78 ARG ILE 79 THR LEU 82 HIS SER 78 ARG ILE 79 THR LEU 82 TYR SER 78 ARG ILE 79 VAL LEU 82 PHE SER 78 ARG ILE 79 VAL LEU 82 HIS SER 78 ARG ILE 79 VAL LEU 82 TYR SER 78 ASP ILE 79 LEU LEU 82 PHE SER 78 ASP ILE 79 LEU LEU 82 HIS SER 78 ASP ILE 79 LEU LEU 82 TYR SER 78 ASP ILE 79 MET LEU 82 PHE SER 78 ASP ILE 79 MET LEU 82 HIS SER 78 ASP ILE 79 MET LEU 82 TYR SER 78 ASP ILE 79 THR LEU 82 PHE SER 78 ASP ILE 79 THR LEU 82 HIS SER 78 ASP ILE 79 THR LEU 82 TYR SER 78 ASP ILE 79 VAL LEU 82 PHE SER 78 ASP ILE 79 VAL LEU 82 HIS SER 78 ASP ILE 79 VAL LEU 82 TYR
SER 78 GLN ILE 79 LEU LEU 82 PHE SER 78 GLN ILE 79 LEU LEU 82 HIS SER 78 GLN ILE 79 LEU LEU 82 TYR SER 78 GLN ILE 79 MET LEU 82 PHE SER ,78 GLN ILE 79 MET LEU 82 HIS SER 78 GLN ILE 79 MET LEU 82 TYR SER 78 GLN ILE 79 THR LEU 82 PHE SER 78 GLN ILE 79 THR LEU 82 HIS SER 78 GLN ILE 79 THR LEU 82 TYR SER 78 GLN ILE 79 VAL LEU 82 PHE SER 78 GLN ILE 79 VAL LEU 82»HIS SER 78 GLN ILE 79 VAL LEU 82 TYR SER 78 HIS ILE 79 LEU LEU 82 PHE SER 78 HIS ILE 79 LEU LEU 82 HIS SER 78 HIS ILE 79 LEU LEU 82 TYR SER 78 HIS ILE 79 MET LEU 82 PHE SER 78 HIS ILE 79 MET LEU 82 HIS SER 78 HIS ILE 79 MET LEU 82 TYR SER 78 HIS ILE 79 THR LEU 82 PHE SER 78 HIS ILE 79 THR LEU 82 HIS SER 78 HIS ILE 79 THR LEU 82 TYR SER 78 HIS ILE 79 VAL LEU 82 PHE SER 78 HIS ILE 79 VAL LEU 82 HIS SER 78 HIS ILE 79 VAL LEU 82 TYR SER 78 LYS ILE 79 LEU LEU 82 PHE SER 78 LYS ILE 79 LEU LEU 82 HIS SER 78 LYS ILE 79 LEU LEU 82 TYR SER 78 LYS ILE 79 MET LEU 82 PHE SER 78 LYS ILE 79 MET LEU 82 HIS SER 78 LYS ILÉ 79 MET LEU 82 TYR SER 78 LYS ILE 79 THR LEU 82 PHE SER 78 LYS ILE 79 THR LEU 82 HIS SER 78 LYS ILE 79 THR LEU 82 TYR SER 78 LYS ILE 79 VAL LEU 82 PHE SER 78 LYS ILE 79 VAL LEU 82 HIS SER 78 LYS ILE 79 VAL LEU 82 TYR SER 78 TYR ILE 79 LEU LEU 82 PHE SER 78 TYR ILE 79 LEU LEU 82 HIS SER 78 TYR ILE 79 LEU LEU 82 TYR SER 78 TYR ILE 79 MET LEU 82 PHE SER 78 TYR ILE 79 MET LEU 82 HIS SER 78 TYR ILE 79 MET LEU 82 TYR SER 78 TYR ILE 79 THR LEU 82 PHE SER 78 TYR ILE 79 THR LEU 82 HIS SER 78 TYR ILE 79 THR LEU 82 TYR SER 78 TYR ILE 79 VAL LEU 82 PHE SER 78 TYR ILE 79 VAL LEU 82 HIS SER 78 TYR ILE 79 VAL LEU 82 TYR SER 78 ASN ILE 79 LEU VAL 81 THR SER 78 ASN ILE 79 MET VAL 81 THR SER 78 ASN ILE 79 THR VAL 81 THR SER 78 ASN ILE 79 VAL VAL 81 THR SER 78 THR ILE 79 LEU VAL 81 THR SER 78 THR ILE 79 MET VAL 81 THR SER 78 THR ILE 79 THR VAL 81 THR SER 78 THR ILE 79 VAL VAL 81 THR ··« ·
SER 78 ARG ILE 79 LEU VAL 81 THR SER 78 ARG ILE 79 MET VAL 81 THR SER 78 ARG ILE 79 THR VAL 81 THR SER 78 ARG ILE 79 VAL VAL 81 THR SER 78 ASP ILE 79 LEU VAL 81 THR SER 78 ASP ILE 79 MET VAL 81 THR SER 78 ASP ILE 79 THR VAL 81 THR SER 78 ASP ILE 79 VAL VAL 81 THR SER 78 GLN ILE 79 LEU VAL 81 THR SER 78 GLN ILE 79 MET VAL 81 THR SER 78 GLN ILE 79 THR VAL 81 THR SER 78 GLN ILE 79 VAL VAL 81 THR SER 78 HIS ILE 79 LEU VAL 81 THR SER 78 HIS ILE 79 MET VAL 81 THR SER 78 HIS ILE 79 THR VAL 81 THR SER 78 HIS ILE 79 VAL VAL 81 THR SER 78 LYS ILE 79 LEU VAL 81 THR SER 78 LYS ILE 79 MET VAL 81 THR SER 78 LYS ILE 79 THR VAL 81 THR SER 78 LYS ILE 79 VAL VAL 81 THR SER 78 TYR ILE 79 LEU VAL 81 THR SER 78 TYR ILE 79 MET VAL 81 THR SER 78 TYR ILE 79 THR VAL 81 THR SER 78 TYR ILE 79 VAL VAL 81 THR ASN 76 HIS VAL 81 THR LEU , 82 PHE í ASN 76 HIS VAL 81 THR LEU 82 HIS ASN 76 HIS VAL 81 THR LEU 82 TYR ASN 76 HIS ILE 79 LEU LEU 82 PHE ASN 76 HIS ILE 79 LEU LEU 82 HIS ASN 76 HIS ILE 79 LEU LEU 82 TYR ASN 76 HIS ILE 79 MET LEU 82 PHE ASN 76 HIS ILE 79 MET LEU 82 HIS ASN 76 HIS ILE 79 MET LEU 82 TYR ASN 76 HIS ILE 79 THR LEU 82 PHE ASN 76 HIS ILE 79 THR LEU 82 HIS ASN 76 HIS ILE 79 THR LEU 82 TYR ASN 76 HIS ILE 79 VAL LEU 82 PHE ASN 76 HIS ILE 79 VAL LEU 82 HIS ASN 76 HIS ILE 79 VAL LEU 82 TYR ASN 76 HIS ILE 79 LEU VAL 81 THR ASN 76 HIS ILE 79 MET VAL 81 THR ASN 76 HIS ILE 79 THR VAL 81 THR ASN 76 HIS ILE 79 VAL VAL 81 THR ASN 76 HIS SER 78 ASN LEU 82 PHE ASN 76 HIS SER 78 ASN LEU 82 HIS ASN 76 HIS SER 78 ASN LEU 82 TYR ASN 76 HIS SER 78 THR LEU 82 PHE ASN 76 HIS SER 78 THR LEU 82 HIS ASN 76 HIS SER 78 THR LEU 82 TYR ASN 76 HIS SER 78 ARG LEU 82 PHE ASN 76 HIS SER 78 ARG LEU 82 HIS ASN .76 HIS SER 78 ARG LEU 82 TYR ASN 76 HIS SER 78 ASP LEU 82 PHE ASN 76 HIS SER 78 ASP LEU 82 HIS ASN 76 HIS SER 78 ASP LEU 82 TYR ASN .76 HIS SER 78 GLN LEU 82 PHE < . ·’ '· * í ί . * Λ·..
ASN 76 HIS SER 78 GLN LEU 82 HIS ASN 76 HIS SER 78 GLN LEU 82 TYR ASN 76 HIS SER 78 HIS LEU 82 PHE ASN 76 HIS SER 78 HIS LEU 82 HIS ASN 76 HIS SER 78 HIS LEU 82 TYR ASN 76 HIS SER 78 LYS LEU 82 PHE ASN 76 HIS SER 78 LYS LEU 82 HIS ASN 76 HIS SER 78 LYS LEU 82 TYR ASN 76 HIS SER 78 TYR LEU 82 PHE ASN 76 HIS SER 78 TYR LEU 82 HIS ASN 76 HIS SER 78 TYR LEU 82 TYR ASN 76 HIS SER 78 ASN VAL 81 THR ASN 76 HIS SER 78 THR VAL 81 THR ASN 76 HIS SER 78 ARG VAL 81 THR ASN 76 HIS SER 78 ASP VAL 81 THR ASN 76 HIS SER 78 GLN VAL 81 THR ASN 76 HIS SER 78 HIS VAL 81 THR ASN 76 HIS SER 78 LYS VAL 81 THR ASN 76 HIS SER 78 TYR VAL 81 THR ASN 76 HIS SER 78 ASN ILE 79 LEU ASN 76 HIS SER 78 ASN ILE 79 MET ASN 76 HIS SER 78 ASN ILE 79 THR ASN 76 HIS SER 78 ASN ILE 79 VAL ASN 76 HIS SER 78 THR ILE 79 LEU ASN 76 HIS SER 78 THR ILE 79 MET ASN 76 HIS SER 78 THR ILE 79 THR ’ ASN 76 HIS SER 78 THR ILE 79 VAL ASN 76 HIS SER 78 ARG ILE 79 LEU ASN 76 HIS SER 78 ARG ILE 79 MET ASN 76 HIS SER 78 ARG ILE 79 THR ASN 76 HIS SER 78 ARG ILE 79 VAL ASN 76 HIS SER 78 ASP ILE 79 LEU ASN 76 HIS SER 78 ASP ILE 79 MET ASN 76 HIS SER 78 ASP ILE 79 THR ASN 76 HIS SER 78 ASP ILE 79 VAL ASN 76 HIS SER 78 GLN ILE 79 LEU ASN 76 HIS SER 78 GLN ILE 79 MET ASN 76 HIS SER 78 GLN ILE 79 THR ASN 76 HIS SER 78 GLN ILE 79 VAL
ASN 76 HIS SER 78 HIS ILE 79 LEU ASN 76 HIS SER 78 HIS ILE 79 MET ASN 76 HIS SER 78 HIS ILE 79 THR ASN 76 HIS SER 78 HIS ILE 79 VAL ASN 76 HIS SER 78 LYS ILE 79 LEU ASN 76 HIS SER 78 LYS ILE 79 MET ASN 76 HIS SER 78 LYS ILE 79 THR ASN 76 HIS SER 78 LYS ILE 79 VAL ASN 76 HIS SER 78 TYR ILE 79 LEU ASN 76 HIS SER 78 TYR ILE 79 MET ASN 76 HIS SER 78 TYR ILE 79 THR ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 75 ILE VAL 81 THR LEU 82 PHE LEU 75 ILE VAL 81 THR LEU 82 HIS LEU 75 ILE VAL 81 THR LEU 82 TYR LEU 75 MET VAL 81 THR LEU 82 PHE LEU 75 MET VAL 81 THR LEU 82 HIS
X
LEU 75 MET VAL 81 THR LEU 82 TYR LEU 75 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ILE 79 LEU LEU, 82 PHE LEU 75 ILE ILE 79 LEU LEU 82 HIS LEU 75 ILE ILE 79 LEU LEU 82 TYR LEU 75 ILE ILE 79 MET LEU 82 PHE LEU 75 ILE ILE 79 MET LEU 82 HIS LEU 75 ILÉ ILE 79 MET LEU 82 TYR LEU 75 ILE ILE 79 THR LEU 82 PHE LEU 75 ILE ILE 79 THR LEU 82 HIS LEU 75 ILE ILE 79 THR LEU 82 TYR LEU 75 ILE ILÉ 79 VAL LEU 82 PHE LEU 75 ILE ILE 79 VAL LEU 82 HIS LEU 75 ILE ILE 79 VAL LEU 82 TYR LEU 75 MET ILE 79 LEU LEU 82 PHE LEU 75 MET ILE 79 LEU LEU 82 HIS LEU 75 MET ILE 79 LEU LEU 82 TYR LEU 75 MET ILÉ 79 MET LEU 82 PHE LEU 75 MET ILE 79 MET LEU 82 HIS LEU 75 MET ILE 79. MET LEU 82 TYR LEU 75 MET ILÉ 79 THR LEU 82 PHE LEU 75 MEŤ ILE 79 THR LEU 82 HIS LEU 75 MET ILE 79 THR LEU 82 TYR LEU 75 MET ILE 79 VAL LEU 82 PHE LEU 75 MET ILE 79 VAL LEU 82 HIS LEU 75 MET ILÉ 79 VAL LEU 82 TYR LEU 75 VAL ILE 79 LEU LEU 82 PHE LEU 75 VAL ILE 79 LEU LEU 82 HIS LEU 75 VAL ILE 79 LEU LEU 82 TYR LEU 75 VAL ILE 79 MET LEU 82 PHE LEU 75 VÁL ILE 79 MET LEU 82 HIS LEU 75 VAL ILE 79 MET LEU 82 TYR LEU 75 VAL ILE 79 THR LEU 82 PHE LEU 75 VAL ILE 79 THR LEU 82 HIS LEU 75 VAL ILE 79 THR LEU 82 TYR LEU 75 VAL ILE 79 VAL LEU 82 PHE LEU 75 VAL ILE 79 VAL LEU 82 HIS LEU 75 VAL ILE 79 VAL LEU 82 TYR LEU 75 ILE ILE 79 LEU VAL 81 THR LEU 75 ILE ILE 79 MET VAL 81 THR LEU 75 ILE ILE 79 THR VAL 81 THR LEU 75 ILE ILE 79 VAL VAL 81 THR LEU 75 MET ILE 79 LEU VAL 81 THR LEU 75 MET ILE 79 MET VAL 81 THR LEU 75 MET ILE 79 THR VAL 81 THR LEU 75 MET ILE 79 VAL VAL 81 THR LEU 75 VAL ILE 79 LEU VAL 81 THR LEU 75 VAL ILE 79 MET VAL 81 THR LEU 75 VAL ILE 79 THR VAL 81 THR LEU 75 VAL ILE 79 VAL VAL 81 THR LEU 75 ILE SER 78 ASN LEU 82 PHE LEU 75 ILE SER 78 ASN LEU 82 HIS LEU 75 ILE SER 78 ASN LEU 82 TYR LEU 75 ILE SER 78 THR LEU 82 PHE
LEU 75 ILE SER 78 THR LEU 82 HIS LEU 75 ILE SER 78 THR LEU 82 TYR LEU 75 ILE SER 78 ARG LEU 82 PHE LEU 75 ILE SER 78 ARG LEU 82 HIS LEU 75 ILE SER 78 ARG LEU 82 TYR LEU 75 ILE SER 78 ASP LEU 82 PHE LEU 75 ILE SER 78 ASP LEU 82 HIS LEU 75 ILE SER 78 ASP LEU 82 TYR LEU 75 ILE SER 78 GLN LEU ,82 PHE LEU 75 ILE SER 78 GLN LEU 82 HIS LEU 75 ILE SER 78 GLN LEU 82 TYR LEU 75 ILE SER 78 HIS LEU 82 PHE LEU 75 ILE SER 78 HIS LEU 82 HIS LEU 75 ILE SER 78 HIS LEU 82 TYR LEU 75 ILE SER 78 LYS LEU 82 PHE LEU 75 ILE SER 78 LYS LEU 82 HIS LEU 75 ILE SER 78 LYŠ LEU 82 TYR LEU 75 ILE SER 78 TYR LEU 82 PHE LEU 75 ILE SER 78 TYR LEU 82HIS LEU 75 ILE SER 78 TYR LEU 82 TYR LEU 75 MET SER 78 ASN LEU 82 PHE LEU 75 MET SER 78 ASN LEU 82 HIS LEU 75 MET SER 78 ASN LEU 82 TYR LEU 75 MET SER 78 THR LEU 82 PHE LEU 75 MET SER 78 THR LEU 82 HIS LEU 75 MET SER 78 THR LEU 82 TYR LEU 75 MET SER 78 ARG LEU 82 PHE LEU 75 MET SER 78 ARG LEU 82 HIS LEU 75 MET SER 78 ARG LEU 82 TYR LEU 75 MET SER 78 ASP LEU 82 PHE LEU 75 MET SER 78 ASP LEU 82 HIS LEU 75 MET SER 78 ASP LEU 82 TYR LEU 75 MET SER 78 GLN LEU 82 PHE LEU 75 MET SER 78 GLN LEU 82 HIS LEU 75 MET SER 78 GLN LEU 82 TYR LEU 75 MET SER 78 HIS LEU 82 PHE LEU 75 MET SER 78 HIS LEU 82 HIS LEU 75 MET SER 78 HIS LEU 82 TYR LEU 75 MET SER 78 LYS LEU 82 PHE LEU 75 MET SER 78 LYS LEU 82 HIS LEU 75 MET SER 78 LYS LEU 82 TYR LEU 75 MET SER 78 TYR LEU 82 PHE LEU 75 MET SER 78 TYR LEU 82 HIS LEU 75 MET SER 78 TYR LEU 82 TYR LEU 75 VAL SER 78 ASN LEU 82 PHE LEU 75 VAL SER 78 ASN LEU 82 HIS LEU 75 VAL SER 78 ASN LEU 82 TYR LEU 75 VAL SER 78 THR LEU 82 PHE LEU 75 VAL SER 78 THR LEU 82 HIS LEU 75 VAL SER 78 THR LEU 82 TYR LEU 75 VAL SER 78 ARG LEU 82 PHE LEU 75 VAL SER 78 ARG LEU 82 HIS LEU 75 VAL SÉR 78 ARG LEU 82 TYR LEU 75 VAL SER 78 ASP LEU 82 PHE LEU 75 VAL SER 78 ASP LEU 82 HIS LEU 75 VAL SER 78 ASP LEU 82 TYR
LEU 75 VAL SER 78 GLN LEU 82 PHE LEU 75 VAL SER 78 GLN LEU 82 HIS LEU 75 VAL SER 78 GLN LEU 82 TYR LEU 75 VAL SER 78 HIS LEU 82 PHE LEU 75 VAL SER 78 HIS LEU 82 HIS LEU 75 VAL SER 78 HIS LEU 82 TYR LEU 75 VAL SER 78 LYS LEU 82 PHE LEU 75 VAL SER 78 LYS LEU 82 HIS LEU 75 VAL SER 78 LYS LEU 82 TYR LEU 75 VAL SER 78 TYR LEU 82 PHE LEU 75 VAL SER 78 TYR LEU 82 HIS LEU 75 VAL SER 78 TYR LEU 82 TYR LEU 75 ILE SER 78 ASN VAL 81 THR LEU 75 ILE SER 78 THR VAL 81 THR LEU 75 ILE SER 78 ARG VAL 81 THR LEU 75 ILE SER 78 ASP VAL 81 THR LEU 75 ILE SER 78 GLN VAL 81 THR LEU 75 ILE SER 78 HIS VAL 81 THR LEU 75 ILE SER 78 LYS VAL 81 THR LEU 75 ILE SER 78 TYR VAL 81 TOR LEU 75 MET SER 78 ASN VAL 81 TOR LEU 75 MET SER 78 TOR VAL 81 TOR LEU 75 MET SER 78 ARG VAL 81 TOR LEU 75 MET SER 78 ASP VAL 81 THR LEU 75 MEŤ SER 78 GLN VAL 81 TOR LEU 75 MET SER 78 HIS VAL 81 TOR · LEU 75 MET SER 78 LYS VÁL 81 TOR LEU 75 MET SER 78 TYR VAL 81 TOR LEU 75 VAL SER 78 ASN VAL 81 TOR LEU 75 VAL SER 78 THR VAL 81 TOR LEU 75 VAL SER 78 ARG VAL 81THR LEU 75 VAL SER 78 ASP VAL 81 TOR LEU 75 VAL SER 78 GLN VAL 81 TOR LEU 75 VAL SER 78 HIS VAL 81 TOR LEU 75 VAL SER 78 LYS VAL 81 TOR LEU 75 VAL SER 78 TYR VAL 81 TOR LEU 75 ILE SER 78 ASN ILE 79 LEU LEU 75 ILE SER 78 ASN ILE 79 MET LEU 75 ILE SER 78 ASN ILE 79 TOR LEU 75 ILE SER 78 ASN ILE 79 VAL LEU 75 ILE SER 78 THR ILE 79 LEU LEU 75 ILE SER 78 THR ILE 79 MET LEU 75 ILE SER 78 THR ILE 79 TOR LEU 75 ILE SER 78 THR ILE 79 VAL LEU 75 ILE SER 78 ARG ILE 79 LEU LEU 75 ILE SER 78 ARG ILE 79 MET LEU 75 ILE SER 78 ARG ILE 79 TOR LEU 75 ILE SER 78 ARG ILE 79 VAL LEU 75 ILE SER 78 ASP ILE 79 LEU LEU 75 ILE SER 78 ASP ILE 79 MET LEU 75 ILE SER 78 ASP ILE 79 THR LEU 75 ILE SER 78 ASP ILE 79 VAL LEU 75 ILE SER 78 GLN ILE 79 LEU LEU 75 ILE SER 78 GLN ILE 79 MET LEU 75 ILE SER 78 GLN ILE 79 TOR LEU 75 ILE SER 78 GLN ILE 79 VAL
···
LEU 75 ILE SER 78 HIS ILE 79 LEU LEU 75 ILE SER 78 HIS ILE 79 MEŤ LEU 75 ILE SER 78 HIS ILE 79 THR LEU 75 ILE SER 78 HIS ILE 79 VAL LEU 75 ILE SER 78 LYS ILE 79 LEU LEU 75 ILE SER 78 LYS ILE 79 MET LEU 75 ILE SER 78 LYS ILE 79 THR LEU 75 ILE SER 78 LYS ILE 79 VAL LEU 75 ILE SER 78 TYR ILE 79 LEU LEU 75 ILE SER 78 TYR ILE 79 MET LEU 75 ILE SER 78 TYR ILE 79 THR LEU 75 ILE SER 78 TYR ILE 79 VAL LEU 75 MET SER 78 ASN ILE 79 LEU LEU 75 MET SER 78 ASN ILE 79 MEŤ LEU 75 MET SER 78 ASN ILE 79 THR LEU 75 MET SER 78 ASN ILE 79 VAL LEU 75 MET SER 78 THR ILE 79 LEU LEU 75 MET SER 78 THR ILE 79 MET LEU 75 MET SER 78 THR ILE 79 THR LEU 75 MET SER 78 THR ILE 79 VAL LEU 75 MET SER 78 ARG ILE 79 LEU LEU 75 MET SER 78 ARG ILE 79 MET LEU 75 MET SER 78 ARG ILE 79 THR LEU 75 MET SÉR 78 ARG ILE 79 VAL LEU 75 MET SER 78 ASP ILE 79 LEU ’ LEU 75 MET SER 78 ASP ILE'79 MET LEU 75 MET SER 78 ASP ILE 79 THR LEU 75 MEŤ SER 78 ASP ILE 79 VAL' LEU 75 MET SER 78 GLN ILE 79 LEU LEU 75 MET SER 78 GLN ILE 79 MET ' LEU 75 MET SER 78 GLN ILE 79 THR LEU 75 MET SER 78 GLN ILE .79 VAL LEU 75 MET SER 78 HIS ILE 79 LEU LEU 75 MET SER 78 HIS ILE 79 MET LEU 75 MET SER 78 HIS ILE 79 THR LEU 75 MET SER 78 HIS ILE 79 VAL LEU 75 MET SER 78 LYS ILE 79 LEU LEU 75 MET SER 78 LYS ILE 79 MET LEU 75 MET SER 78 LYS ILE 79 THR LEU 75 MET SER 78 LYS ILE 79 VAL LEU 75 MET SER 78 TYR ILE 79 LEU LEU 75 MET SER 78 TYR ILE 79 MET LEU 75 MET SER 78 TYR ILE 79 THR LEU 75 MET SER 78 TYR ILE 79 VAL LEU 75 VAL SER 78 ASN ILE 79 LEU LEU 75 VAL SER 78 ASN ILE 79 MET LEU 75 VAL SER 78 ASN ILE 79 THR LEU 75 VAL SER 78 ASN ILE 79 VAL LEU 75 VAL SER 78 THR ILE 79 LEU LEU 75 VAL SER 78 THR ILE 79 MET LEU 75 VAL SER 78 THR ILE 79 THR LEU 75 VAL SER 78 THR ILE 79 VAL LEU 75 VAL SER 78 ARG ILE 79 LEU LEU 75 VAL SER 78 ARG ILE 79 MET LEU 75 VAL SER 78 ARG ILE 79 THR LEU 75 VAL SER 78 ARG ILE 79 VAL
LEU 75 VAL SER 78 ASP ILE 79 LEU LEU 75 VAL SER 78 ASP ILE 79 MET LEU 75 VAL SER 78 ASP ILE 79 THR LEU 75 VAL SER 78 ASP ILE 79 VAL LEU 75 VAL SER 78 GLN ILE 79 LEU LEU 75 VAL SER 78 GLN ILE 79 MET ‘ LEU 75 VAL SEŘ,78 GLN ILE 79 THR LEU 75 VAL SER 78 GLN ILE 79 VAL LEU 75 VAL SER 78 HIS ILE 79 LEU LEU 75 VAL SÉR 78 HIS ILE 79MET LEU 75 VAL SER 78 HIS ILE 79 THR LEU 75 VAL SER 78 HIS ILE ’79 VAL LEU 75 VAL SER 78 LYS ILE 79 LEU LEU 75 VAL SER 78 LYS ILE 79 MET LEU 75 VAL SER 78 LYS ILE 79 THR LEU 75 VAL SER 78 LYS ILE 79 VAL LEU 75 VAL SER 78 TYR ILE 79 LEU LEU 75 VAL SER 78 TYR ILE 79 MET LEU 75 VAL SER 78 TYR ILE 79 THR LEU 75 VAL SER 78 TYR ILE 79 VAL LEU 75 ILE ASN 76 HIS LEU 82 PHE LEU 75 ILE ASN 76 HIS LEU 82 HIS LEU 75 ILE ASN 76 HIS LEU 82 TYR LEU 75 MET ASN 76 HIS LEU 82 PHE LEU 75 MET ASN 76 HIS LEU 82 HIS LEU 75 MET ASN 76 HIS LEU 82 TYR LEU 75 VAL ASN 76 HIS LEU 82 PHE ' LEU 75 VAL ASN 76 HIS LEU 82 HIS LEU 75 VAL ASN 76 HIS LEU 82 TYR LEU 75 ILE ASN 76 HIS VAL 81 THR LEU 75 MET ASN 76 HIS VAL 8ÍTHR LEU 75 VAL ASN 76 HIS VAL 81 THR LEU 75 ILE ASN 76 HIS ILE 79 LEU LEU 75 ILE ASN 76 HIS ILE 79 MET LEU 75 ILE ASN 76 HIS ILE 79 THR LEU 75 ILE ASN 76 HIS ILE 79 VAL LEU 75 MET ASN 76 HIS ILE 79 LEU LEU 75 MET ASN 76 HIS ILE 79 MET LEU 75 MET ASN 76 HIS ILE 79 THR LEU 75 MET ASN 76 HIS ILE 79 VAL LEU 75 VAL ASN 76 HIS ILE 79 LEU LEU 75 VAL ASN 76 HIS ILE 79 MET LEU 75 VAL ASN 76 HIS ILE 79 THR LEU 75 VAL ASN 76 HIS ILE 79 VAL LEU 75 ILE ASN 76 HIS SER 78 ASN LEU 75 ILE ASN 76 HIS SER 78 THR LEU 75 ILE ASN 76 HIS SER 78 ARG LEU 75 ILE ASN 76 HIS SER 78 ASP LEU 75 ILE ASN 76 HIS SER 78 GLN LEU 75 ILE ASN 76 HIS SER 78 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS LEU 75 ILE ASN 76 HIS SER 78 TYR LEU 75 MET ASN 76 HIS SER 78 ASN LEU 75 MET ASN 76 HIS SER 78 THR LEU 75 MET ASN 76 HIS SER 78 ARG LEU 75 MET ASN 76 HIS SER 78 ASP
Λ . .*·£·
LEU 75 MET ASN 76 HIS SER 78 GLN
LEU 75 MET ASN 76 HIS SER 78 HIS LEU 75 MET ASN 76 HIS SER 78 LYS LEU 75 MÉTASN 76 HIS SER 78 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN LEU 75 VAL ASN 76 HIS SER 78 THR LEU 75 VAL ASN 76 HIS SER 78 ARG LEU 75 VAL ASN 76 HIS SER .78 ASP LEU 75 VAL ASN 76 HIS SER 78 GLN ,. „ . LEU 75 VAL ASN 76 HIS SER 78 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS LEU 75 VAL ASN 76 HIS SER 78 TYR
Tabulka 5
Čtyřnásobné substituční varianty
SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 TYR SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 TYR , SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 ASN ILE 79 THR VÁL 81 THR LEU 82 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 TYR SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 PHE SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 TYR SER 78 THR ILE 79 LEU VAL 81THRLEŮ 82 PHE SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 TYR SER 78 THR ILE 79 MET VAL 8.1 THR LEU 82 PHE SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 TYR SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 TYR SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 PHE SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 TYR SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 TYR SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 TYR SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 TYR SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 PHE SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 TYR SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 TYR
SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 TYR SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 HIS SEŘ 78 ASP ILE 79 THR VAL 81 THR LEU 82 TYR SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 PHE SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 TYR SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 TYR SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 TYR SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 HIS SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 TYR SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 PHE SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 TYR SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 TYR SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 TYR SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 TYR SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 TYR SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 HIS SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 TYR SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 PHE SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 TYR SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 TYR SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 TYR SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 TYR SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 PHE SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 HIS
SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 TYR ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 PHE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 HIS ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 TYR ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 PHE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 HIS . ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 TYR ASN 76 HIS ILE 79 VAL VAL 81 THR LEU: 82 PHE ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 TYR ASN 76 HIS ŠEŘ 78 GLN VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 TYR ASN 76 HIS ŠER 78 HIS VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 TYR ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 TYR ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 TYR ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 TYR ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 TYR ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 TYR ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 PHE ♦ · · · « 4 · ·.♦-.·· • . · e ··>'·
ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 TYR ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 TYR ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 TYR ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 TYR ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 PHE ASN 76HÍSSER 78 ARG ILE 79 THR LEU 82 HIS ASN 76 HIS ŠER 78 ARG ILE 79 THR LEU 82 TYR ASN 76 HIS SER 78 ARGILE 79 VAL LEU 82 PHE ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 HIS ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 TYR ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 TYR ASN 76 HIS SÉR 78 ASP ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 TYR ASN 76 HIS ŠER 78 ASP ILE 79 THR LEU 82 PHE ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 TYR ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 PHE ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 HIS ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 TYR ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 TYR ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 TYR ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 PHE ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 TYR ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 PHE ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 HIS ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 TYR ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 TYR ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 TYR ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 PHE ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 TYR ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 PHE ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 HIS ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 TYR ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 TYR '2 ·· ·« ·· ··
9 9 9 9-9 .9.-9 99 9
9 9 9 9 9
9.- 9 · · · ···· 99 9 9
ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 HIS ASN 76 HIS SER. 78 LYS ILE 79 MET LEU 82 TYR ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 PHE ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 TYR ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 PHE ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 HIS ASN 76 HIS SER 78 LYS ILE 79. VAL LEU 82 TYR ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 TYR ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 TYR ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 PHE ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 TYR ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 PHE ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 HIS ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 TYR ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR ASN 76 HIS SER 78 THR ILE *79 LEU VAL 81 THR ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 75 ILE ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ILE 79 LEU VAL 81 THR LEU 82 TYR ·· »· ·« ·· ·«, ··« · · · » * .. · · .·.··*·. v '·'· · - «'·· · · · • · · . · · · · · • Β · · · · ·♦····· · · · ·.
LEU 75 ILE ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET ILE 79 LEU VAL 81 THR LEU . 82 PHE LEU 75 MET ILE 79 LEU VAL 81 THR LEU .82 HIS
LEU 75 MET ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ILÉ 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 THR VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ARG VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ARG VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ARG VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ASP VAL 81 THR LEU 82 PHE
LEU 75 ILE SER 78 ASP VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASP VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 GLN VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 GLN VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 GLN VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 HIS VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 HIS VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 HIS VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 LYS VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 LYS VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 LYS VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 TYR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 TYR VAL 81 THR LEU 82 HIS
LEU 75 ILE SER 78 TYR VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 THR VAL 81 THR LEU 82 PHE LEU 75 MEŤ SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 THR VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ARG VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ARG VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ARG VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ASP VAL 81 THR LEU 82 PHE LEU 75 MET SÉR 78 ASP VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASP VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 GLN VAL 81 THR LEU 82 PHE LEU 75 MET, SER 78 GLN VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 GLN VAL 81 THR LEŮ 82 TYR LEU 75 MET SER 78 HIS VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 HIS VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 HIS VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 LYS VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 LYS VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 LYS VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 TYR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 TYR VAL 81THR LEU 82 HIS LEU 75 MET SER 78 TYR VAL 81THR LEU 82 TYR LEU 75 VAL SER 78 ASN VAL 8Ί THR LEU 82 PHE LEU 75 VAL SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASN VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 THR VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ARG VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ARG VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ARG VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 A$P VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ASP VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASP VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 GLN VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 GLN VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 GLN VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 HIS VAL 81 THR LEU 82 PHE
LEU 75 VAL SER 78 HIS VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 HIS VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 LYS VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 LYS VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 LYS VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 TYR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 TYR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 TYR VAL 81 THR LEU 82 TYR LEU 75 ILE SER ,78 ASN ILE 79 LEU LEU 82 PHE
LEU 75 ILE SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 ILE SÉR 78 ASN ILE 79 LEU LEU 82 TYR LEU 75 ILE ŠER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 MET LEU 82 HIS LEU . 75 ILE SER 78 ASN ILE 79 MET LEU 82 TYR LEU 75 ILE SER 78 ASN ILE 79 THR LEU 82 PHE
··· - ···
LEU 75 ILE SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 THR LEU 82 TYR LEU 75 ILE SER 78 ASN ILE 79 VAL LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 VAL LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 VAL LEU 82 TYR LEU 75 ILE SER 78 THR ILE 79 LEU LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 LEU LEU 82 TYR LEU 75 ILE SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 MET LEU. 82 HIS LEU 75 ILE SER 78 THR ILE 79 MET LEU 82 TYR LEU 75 ILE ŠER 78 THR ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 THR LEU 82 TYR LEU 75 ILE SER 78 THR ILE 79 VAL LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 VAL LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 VAL LEU 82 TYR LEU 75 ILE SER 78 ARG ILE 79 LEU LEU 82 PHE LEU 75 ILE SER 78 ARG ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 ARG ILE 79 LEU LEU 82 TYR LEU 75 ILE SER 78 ARG ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 ARG ILE 79 MET LEU 82 HIS LEU 75 ILE SER 78 ARG ILE 79 MET LEU 82 TYR LEU 75 ILE SER 78 ARG ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 ARG ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 ARG ILE 79 THR LEŮ 82 TYR LEU 75 ILE SER 78 ARG ILE 79 VAL LEU 82 PHE LEU 75 ILE SER 78 ARG ILE 79 VAL LEU 82 HIS ' LEU 75 ILE SER 78 ARG ILE 79 VAL LEU 82 TYR LEU 75 ILE SER 78 ASP ILE 79 LEU LEU 82 PHE LEU 75 ILE SER 78 ASP ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 ASP ILE 79 LEU LEU 82 TYR LEU 75 ILE SER 78 ASP ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 ASP ILE 79 MET LEU 82 HIS LEU 75 ILE SER 78 ASP ILE 79 MET LEU 82 TYR LEU 75 ILE SER 78 ASP ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 ASP ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 ASP ILE 79 THR LEU 82 TYR LEU 75 ILE SER 78 ASP ILE 79 VAL LEU 82 PHE LEU 75 ILE SER 78 ASP ILE 79 VAL LEU 82 HIS LEU 75 ILE SER 78 ASP ILE 79 VAL LEU 82 TYR LEU 75 ILE SER 78 GLN ILE 79 LEU LEU 82 PHE LEU 75 ILE SER 78 GLN ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 GLN ILE 79 LEU LEU 82 TYR LEU 75 ILE SER 78 GLN ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 GLN ILE 79 MET LEU 82 HIS LEU 75 ILE SER 78 GLN ILE 79 MET LEU 82 TYR LEU 75 ILE SER 78 GLN ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 GLN ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 GLN ILE 79 THR LEU 82 TYR LEU 75 ILE SER 78 GLN ILE 79 VAL LEU 82 PHE LEU 75 ILE SER 78 GLN ILE 79 VAL LEU 82 HIS LEU 75 ILE SER 78 GLN ILE 79 VAL LEU 82 TYR LEU 75 ILE SER 78 HIS ILE 79 LEU LEU .82 PHE LEU 75 ILE SER 78 HIS ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 HIS ILE 79 LEU LEU 82 TYR
• ·
LEU 75 ILE SER 78 HIS ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 HIS ILE 79 MET LEU 82 HIS LEU 75 ILE SER 78 HIS ILE 79 MET LEU 82 TYR LEU 75 ILE SER 78 HIS ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 HIS ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 HIS ILE 79 THR LEU 82 TYR LEU 75 ILE SER 78 HIS ILE 79 VAL LEU 82 PHE LEU 75 ILE SER 78 HIS ILE 79 VAL LEU 82 HIS LEU 75 ILE SER 78 HIS ILE 79 VAL LEU 82 TYR LEU 75 ILE SER 78 LYS ILE 79 LEU LEU 82 PHE LEU 75 ILE SER 78 LYS ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 LYS ILE 79 LEU LEU 82 TYR LEU 75 ILE SER 78 LYS ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 LYS ILE 79 MET LEU 82 HIS LEU 75 ILE SER 78 LYS ILE 79 MET LEU 82 TYR LEU 75 ILE SER 78 LYS ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 LYS ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 LYS ILE 79 THR LEU 82 TYR LEU 75 ILE SER 78 LYS ILE 79 VAL LEU 82 PHE LEU 75 ILE SER 78 LYS ILE 79 VAL LEU 82 HIS LEU 75 ILE SER 78 LYS ILE 79 VAL LEU 82 TYR LEU 75 ILE SER 78 TYR ILE 79 LEU LEU 82 PHE LEU 75 ILE SER 78 TYR ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 TYR ILE 79 LEU LEU 82 TYR LEU 75 ILE SER 78 TYR ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 TYR ILE 79 MET LEU 82 HIS LEU 75 ILE SER 78 TYR ILE 79 MET LEU 82 TYR . LEU 75 ILE SER 78 TYR ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 TYR ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 TYR ILE 79 THR LEU 82 TYR LEU 75 ILE SER 78 TYR ILE 79 VAL LEU 82 PHE LEU 75 ILE SER 78 TYR ILE 79 VAL LEU 82 HIS LEU 75 ILE SER 78 TYR ILE 79 VAL LEU 82 TYR
LEU 75 MET SER 78 ASN ILE 79 LEU LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 LEU LEU 82 TYR LEU 75 MET SER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 MET LEU 82 TYR LEU 75 MET SER 78 ASN ILE 79 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 THR LEU 82 TYR LEU 75 MET SER 78 ASN ILE 79 VAL LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 VAL LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 VAL LEU 82 TYR LEU 75 MET SER 78 THR ILE 79 LEU LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 LEU LEU 82 TYR LEU 75 MET SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 MET LEU 82 TYR LEU 75 MET SER 78 THR ILE 79 THR LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 THR LEU 82 TYR LEU 75 MET SER 78 THR ILE 79 VAL LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 VAL LEU 82 HIS
LEU 75 MET SER 78 THR ILE 79 VAL LEU 82 TYR LEŮ. 75 MET SER 78 ARG ILE 79 LEU LEU 82 PHE LEU 75 MET SER 78 ARG ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 ARG ILE 79 LEU LEU 82 TYR LEU 75 MET SER 78 ARG ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 ARG ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 ARG ILE 79 MET LEU 82 TYR . LEU 75 MET SER 78 ARG ILE 79 THR LEU 82 PHE LEU 75 MET SER 78 ARG ILE 79, THRLEU 82 HIS LEU 75 MET ŠER 78 ARG ILE 79 THR LEU 82 TYR . LEU 75 MET SER 78 ARG ILE 79 VAL LEU 82 PHE t LEU 75 MET SER 78 ARG ILE 79 VAL LEU 82 HIS LEU 75 MET SER 78 ARG ILE 79 VAL LEU 82 TYR LEU 75 MET SER 78 ASP ILE 79 LEU LEU 82 PHE LEU 75 MET SER 78 ASP ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 ASP ILE 79 LEU LEU 82 TYR LEU 75 MET SER 78 ASP ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 ASP ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 ASP ILE 79 MET LEU 82 TYR LEU 75 MET SER 78 ASP ILE 79 THR LEU 82 PHE LEU 75 MET SER 78 ASP ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 ASP ILE 79 THR LÉU 82 TYR LEU 75 MET SER 78 ASP ILE 79 VAL LEU 82 PHE LEU 75 MET SER 78 ASP ILE 79 VAL LEU 82 HIS LEU 75 MET SER 78 ASP ILE 79 VAL LEU 82 TYR LEU 75 MET SER 78 GLNILE 79 LEŮ LEU 82 PHE LEU 75 MET SER 78 GLN ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 GLN ILE 79 LEU LÉU 82 TYR ' LEU 75 MET SER 78 GLN ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 GLN ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 GLN ILE 79 MET LEU 82 TYR LEU 75 MET SER 78 GLN ILE 79 THR LEU 82 PHE LEU 75 MET SER 78 GLN ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 GLN ILE 79 THR LEU 82 TYR LEU 75 MET SER 78 GLN ILE 79 VAL LEU 82 PHE LEU 75 MET SER 78 GLN ILE 79 VAL LEU 82 HIS LEU 75 MET SER 78 GLN ILE 79 VAL LEU 82 TYR LEU 75 MET SER 78 HIS ILE 79 LEU LEU 82 PHE LEU 75 MET SER 78 HIS ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 HIS ILE 79 LEU LEU 82 TYR LEU 75 MET SER 78 HIS ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 HIS ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 HIS ILE 79 MET LEU 82 TYR LEU 75 MET SER 78 HIS ILE 79 THR LEU 82 PHE LEU 75 MET SER 78 HIS ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 HIS ILE 79 THR LEU 82 TYR LEU 75 MET SER 78 HIS ILE 79 VAL LEU 82 PHE LEU 75 MET SER 78 HIS ILE 79 VAL LEU 82 HIS LEU 75 MET SER 78 HIS ILE 79 VAL LEU 82 TYR LEU 75 MET SER 78 LYS ILE 79 LEU LEU 82 PHE LEU 75 MET SER 78 LYS ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 LYS ILE 79 LEU LEU 82 TYR LEU 75 MET SER 78 LYS ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 LYS ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 LYS ILE 79 MET LEU 82 TYR LEU 75 MET SER 78 LYS ILE 79 THR LEU 82 PHE
LEU 75.MET SER 78 LYS ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 LYS ILE 79 THR LEU 82 TYR LEU 75 MET SER 78 LYS ILE 79 VAL LEU 82 PHE .
LEU 75 MET SER 78 LYS ILE 79 VAL LEU 82 HIS LEU 75 MET SER 78 LYS ILE 79 VAL LEU 82 TYR LEU 75 MET SER 78 TYR ILE 79 LEU LEU 82 PHE LEU 75 MET SER 78 TYR ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 TYR ILE 79 LEU LEU 82 TYR LEU 75 MET SER 78 TYR ILE .79 MET LEU 82 PHE LEU 75 MET SER 78 TYR ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 TYR ILE 79 MET LEU 82 TYR LEU 75 MET SER 78 TYR ILE 79 THR LEU 82 PHE LEU 75 MET SER 78 TYR ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 TYR ILE 79 THR LEU 82 TYR LEU 75 MET SER 78 TYR ILE 79 VAL LEU 82 PHE LEU 75 MET SER 78 TYR ILE 79 VAL LEU 82 HIS LEU 75 MET SER 78 TYR ILE 79 VAL LEU 82 TYR LEU 75 VAL SER 78 ASN ILE 79 LEU LEU 82 PHE LEU 75 VAL SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 VAL SER 78 ASN ILE 79 LEU LEU 82 TYR LEU 75 VAL SER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 VAL SÉR 78 ASN ILE 79 MEŤ LEU 82 HIS LEU 75 VAL SER 78 ASN ILE 79 MET LEU 82 TYR LEU 75 VAL SER 78 ASN ILE 79 THR LEU 82 PHE LEU 75 VAL SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 VAL SER 78 ASNILE 79 THR LEU 82 TYR ‘ ‘
LEU 75 VAL SER 78 ASN ILE 79 VAL LEU 82 PHE
LEU 75 VAL SER 78 ASN ILE 79 VAL LEU 82 HIS
LEU 75 VAL SER 78 ASN ILE 79 VAL LEU 82 TYR '·' 1 LEU 75 VAL SER 78 THR ILE 79 LEU LEU 82 PHE
LEU 75 VAL SER 78 THR ILE 79 LEU LEU 82 HIS
LEU 75 VAL SER 78 THR ILE 79 LEU LEU 82 TYR
LEU 75 VAL SER 78 THR ILE 79 MET LEU 82 PHE
LEU 75 VAL SER 78 THR ILE 79 MET LEU 82 HIS
LEU 75 VAL SER 78 THR ILE 79 MEŤ LEU 82 TYR
LEU 75 VAL SER 78 THR ILE 79 THR LEU 82 PHE
LEU 75 VAL SER 78 THR ILE 79 THR LEU 82 HIS
LEU 75 VAL SER 78 THR ILE 79 THR LEU 82 TYR
LEU 75 VAL SER 78 THR ILE 79 VAL LEU 82 PHE
LEU 75 VAL SER 78 THR ILE 79 VAL LEU 82 HIS
LEU 75 VAL SER 78 THR ILE 79 VAL LEU 82 TYR
LEU 75 VAL SER 78 ARG ILE 79 LEU LEU 82 PHE
LEU 75 VAL SER 78 ARG ILE 79 LEU LEU 82 HIS
LEU 75 VAL SER 78 ARG ILE 79 LEU LEU 82 TYR
LEU 75 VAL SER 78 ARG ILE 79 MET LEU 82 PHE
LEU 75 VAL SER 78 ARG ILE 79 MET LEU 82 HIS
LEU 75 VAL SER 78 ARG ILE 79 MET LEU 82 TYR
LEU 75 VÁL SER 78 ARG ILE 79 THR LEU 82 PHE
LEU 75 VAL SER 78 ARG ILE 79 THR LEU 82 HIS
LEU 75 VAL SER 78 ARG ILE 79IHR LEU 82 TYR
LEU 75 VAL SER 78 ARG ILE 79 VAL LEU 82 PHE
LEU 75 VAL SER 78 ARG ILE 79 VAL LEU 82 HIS
LEU 75 VAL SER 78 ARG ILE 79 VAL LEU 82 TYR
LEU 75 VAL SER 78 ASP ILE 79 LEU LEU 82 PHE
LEU 75 VÁL SER 78 ASP ILE 79 LEU LEU 82 HIS LEU 75 VAL SÉR 78 ÁSP ÍLE 79 LEU LEU 82 TYR
LEU 75 VAL SER 78 ASP ILE 79 MET LEU 82 PHE LEU 75 VAL SER 78 ASP ILE 79 MET LEU 82 HIS LEU 75 VAL SER 78 ASP ILE 79 MET LEU 82 TYR LEU 75 VAL SER 78 ASP ILE 79 THR LEU 82 PHE LEU 75 VAL SER 78 ASP ILE 79 THR LEU 82 HIS LEU 75 VAL'SER 78 ASP ILE 79 THR LEU 82 TYR LEU 75 VAL SER 78 ASP ILE 79 VAL LEU 82 PHE LEU 75 VAL SER 78 ASP ILE 79 VAL LEU 82 HIS LEU 75 VAL SER 78 ASP ILE 79 VAL LEU 82 TYR LEU 75 VAL ŠER 78 GLN ILE 79 LEU LEU 82 PHE LEU 75 VAL SER 78 GLN ILE 79 LEU LEU 82 HIS LEU 75 VAL SER 78 GLN ILE 79 LEU LEU 82 TYR LEU 75 VAL SER 78 GLN ILE 79 MET LEU 82 PHE LEU 75 VAL SÉR 78 GLN ILE 79 MET LEU 82 HIS LEU 75 VAL SER 78 GLN ILE 79 MET LEU 82 TYR LEU 75 VAL SER 78 GLN ILE 79 THR LEU 82 PHE LEU 75 VAL SER 78 GLN ILE 79 THR LEU 82 HIS LEU 75 VAL SER 78 GLN ILE 79 THR LEU 82 TYR LEU 75 VAL SER 78 GLN ILE 79 VAL LEU 82 PHE LEU 75 VAL SER 78 GLN ILE 79 VAL LEU 82 HIS LEU 75 VAL SER 78 GLN ILE 79 VAL LEU 82 TYR LEU 75 VAL SER 78 HIS ILE 79 LEU LEU 82 PHE LEU 75 VAL SER 78 HIS ILE 79 LEU LEU 82 HIS LEU 75 VAL SER 78 HIS ILE 79 LEU LEU 82 TYR LEU 75 VAL SER 78 HIS ILE 79 MET LEU 82 PHE LEU 75 VAL SER 78 HIS ILE 79 MET LEU 82 HIS LEU 75 VAL SER 78 HIS ILE 79 MET LEU 82 TYR LEU 75 VAL SER 78 HIS ILE 79 THR LEU 82 PHE LEU 75 VAL ŠER 78 HIS ILE 79 THR LEU 82 HIS LEU 75 VAL SER 78 HIS ILE 79 THR LEU 82 TYR LEU 75 VAL SER 78 HIS ILE 79 VAL LEU 82 PHE LEU 75 VAL SER 78 HIS ILE 79 VAL LEU 82 HIS LEU 75 VAL SER 78 HIS ILE 79 VAL LEU 82 TYR LEU 75 VAL SER 78 LYS ILE 79 LEU LEU 82 PHE LEU 75 VAL SER 78 LYS ILE 79 LEU LEU 82 HIS LEU 75 VAL SER 78 LYS ILE 79 LEU LEU 82 TYR LEU 75 VAL SER 78 LYS ILE 79 MET LEU 82 PHE LEU 75 VAL SER 78 LYS ILE 79 MET LEU 82 HIS LEU 75 VAL SER 78 LYS ILE 79 MET LEU 82 TYR LEU 75 VAL SER 78 LYS ILE 79 THR LEU 82 PHE LEU 75 VAL SER 78 LYS ILE 79 THR LEU 82 HIS LEU 75 VAL SER 78 LYS ILE 79 THR LEU 82 TYR LEU 75 VAL SER 78 LYS ILE 79 VAL LEU 82 PHE LEU 75 VAL SER 78 LYS ILE 79 VAL LEU 82 HIS LEU 75 VAL SER 78 LYS ILE 79 VAL LEU 82 TYR LEU 75 VAL SER 78 TYR ILE 79 LEU LEU 82 PHE LEU 75 VAL SER 78 TYR ILE 79 LEU LEU 82 HIS LEU 75 VAL SER 78 TYR ILE 79 LEU LEU 82 TYR LEU 75 VAL SER 78 TYR ILE 79 MET LEU 82 PHE LEU 75 VAL SER 78 TYR ILE 79 MET LEU 82 HIS LEU 75 VAL SER 78 TYR ILE 79 MET LEU 82 TYR LEU 75 VAL SER 78 TYR ILE 79 THR LEU 82 PHE LEU 75 VAL SÉR 78 TYR ILE 79 THR LEU 82 HIS LEU 75 VAL SER 78 TYR ILE 79 THR LEU 82 TYR LEU 75 VAL SER 78 TYR ILE 79 VAL LEU 82 PHE LEU 75 VAL SER 78 TYR ILE 79 VAL LEU 82 HIS • ·
LEU 75 VAL SER 78 TYR ILE 79 VAL LEU 82 TYR LEU 75 ILE SER 78 ASN ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 ILE SER 78 ASN ILE 79 THR VAL 81 THR . LEU 75 ILE SER 78 ASN ILE 79 VAL VAL 81 THR LEU 75 ILE SER 78 THR ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 THR ILE 79 MET VAL 81 THR LEU 75 ILE SER 78 THR ILE 79 THR VAL 81 THR LEU 75 ILE SER 78 THR ILE 79 VAL VAL 81 THR LEU 75 ILE SER 78 ARG ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 ARG ILE 79 MET VAL .81 THR LEU 75 ILE SER 78 ARG ILE 79 THR VAL 81 THR LEU 75 ILE SER 78 ARG ILE 79 VAL VAL 81 THR LEU 75 ILE SER 78 ASP ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 ASP ILE 79 MET VAL 81 THR LEU 75 ILE SER 78 ASP ILE 79 THR VAL 81 THR LEU 75 ILE SER 78 ASP ILE 79 VAL VAL 81 THR LEU 75 ILE SER 78 GLN ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 GLN ILE 79 MET VAL 81 THR LEU 75 ILE SER 78 GLN ILE 79 THR VAL 81 THR LEU 75 ILE SER 78 GLN ILE 79 VAL VAL 81 THR LEU 75 ILE SER 78 HIS ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 HIS ILE 79 MET VAL 81 THR LEU 75 ILE SER 78 HIS ILE 79 THR VAL 81 THR LEU 75 ILE SER 78 HIS ILE 79 VAL VAL 81 THR LEU 75 ILE SER 78 LYS ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 LYS ILE 79 MET VAL 81 THR LEU 75 ILE SER 78 LYS ILE 79 THR VAL 81THR LEU 75 ILE SER 78 LYS ILE 79 VAL VAL 81 THR LEU 75 ILE SER 78 TYR ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 TYR ILE 79 MET VAL 81.THR LEU 75 ILE SER 78 TYR ILE 79 THR VAL 81 THR LEU 75 ILE SER 78 TYR ILE 79 VAL VAL 81 THR LEU 75 MET SER 78 ASN ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 MET SER 78 ASN ILE 79 THR VAL 81 THR LEU 75 MET SER 78 ASN ILE 79 VAL VAL 81 THR LEU 75 MET SER 78 THR ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 THR ILE 79 MET VAL 81 THR LEU 75 MET SER 78 THR ILE 79 THR VAL 81 THR LEU 75 MET SER 78 THR ILE 79 VAL VAL 81 THR LEU 75 MET SER 78 ARG ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 ARG ILE 79 MET VAL 81 THR LEU 75 MET SER 78 ARG ILE 79 THR VAL 81 THR LEU 75 MET SER 78 ARG ILE 79 VAL VAL 81 THR LEU 75 MET SER 78 ASP ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 ASP ILE 79 MET VAL 81 THR LEU 75 MET SER 78 ASP ILE 79 THR VAL 81 THR LEU 75 MET SER 78 ASP ILE 79 VAL VAL 81 THR LEU 75 MET SER 78 GLN ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 GLN ILE 79 MET VAL 81 THR LEU 75 MET SER 78 GLN ILE 79 THR VAL 81 THR LEU 75 MET SER 78 GLN ILE 79 VAL VAL 81 THR LEU 75 MET SER 78 HIS ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 HIS ILE 79 MET VAL 81 THR LEU 75 MET SER 78 HIS ILE 79 THR VAL 81 THR .36
LEU 75 MET SER 78 HIS ILE 79 VAL VAL 81 THR LEU 75 MET SER 78 LYS ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 LYS ILE 79 MET VAL 81 THR LEU 75 MET SER 78 LYS ILE 79 THR VAL 81 THR LEU 75 MET SER 78 LYS ILE 79 VAL VAL 81 -THR ; LEU 75 MET SER 78 TYR ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 TYR ILE 79 MET VAL 81 THR LEU 75 MET SER 78 TYR ILE 79 THR VAL 81 THR LEU 75 MET SER 78 TYR ILE 79 VAL VAL 81 THR LEU 75 VALSER 78 ASN ILE 79 LEU VAL 81 THR LEU 75 VAL SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 VAL SÉR 78 ASN ILE 79 THR VAL 81 THR LEU 75 VALSER 78 ASN ILE 79 VAL VAL 81 THR. LEU 75 VAL SER 78 THR ILE 79 LEU VAL 81 THR LEU 75 VAL SER 78 THR ILE 79 MET VAL 81 THR LEU 75 VAL SER 78 THR ILE 79 THR VAL 81 THR LEU 75 VAL SER 78 THR ILE 79 VAL VAL 81 THR LEU 75 VALSER 78 ARG ILE 79 LEU VAL 81 THR LEU 75 VAL SER 78 ARG ILE 79 MET VAL 81 THR LEU 75 VAL SER 78 ARG ILE 79 THR VAL 81 THR LEU 75 VAL SER 78 ARG ILE 79 VAL VAL 81 THR LEU 75 VAL SER 78 ASP ILE 79 LEU VAL 81 THR LEU 75 VAL SER 78 ASP ILE»79 MET VAL 81 THR LEU 75 VAL SER 78 ASP ILE 79 THR VAL 81 THR LEU 75 VAL SER 78 ASP ILE 79 VAL VAL 81 THR v LEU 75 VAL SER 78 GLN ILE 79 LEU VAL 81 THR LEU 75 VAL SER 78 GLN ILE 79 MET VAL 81THR LEU 75 VAL SER ’ 78 GLN ILE 79 THR VAL 81 THR LEU 75 VAL SER 78 GLN ILE 79 VAL VAL 81 THR LEU 75 VAL SER 78 HIS ILE 79 LEU VAL 81 THR LEU 75 VAL SER 78 HIS ILE 79 MET VAL 81 THR LEU 75 VAL SER 78 HIS ILE 79 THR VAL 81 THR LEU 75 VAL SER 78 HIS ILE 79 VAL VAL 81 THR LEU 75 VAL SER 78 LYS ILE 79 LEU VAL 81 THR LEU 75 VAL SER 78 LYS ILE 79 MET VAL 81 THR LEU 75 VAL SER 78 LYS ILE 79 THR VAL 81 THR LEU 75 VAL SER 78 LYS ILE 79 VAL VAL 81 THR LEU 75 VAL SER 78 TYR ILE 79 LEU VAL 81 THR LEU 75 VAL SER 78 TYR ILE 79 MET VAL 81THR LEU 75 VALSER 78 TYR ILE 79 THR VAL 81 THR LEU 75 VALSER 78 TYR ILE 79 VAL VAL 81 THR LEU 75 ILE ASN 76 HIS VAL 81 THR LEU 82 PHE
LEU 75 ILE ASN 76 HIS VAL 81 THR LEU 82 HIS
LEU 75 ILE ASN 76 HIS VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS VAL 81 THR LEU 82 TYR
LEU 75 ILE ASN 76 HIS ILE 79 LEU LEU 82 PHE
LEU 75 ILE ASN 76 HIS ILE 79 LEU LEU 82 HIS
LEU 75 ILE ASN 76 HIS ILE 79 LEU LEU 82 TYR
LEU 75 ILE ASN 76 HIS ILE 79 MET LEU 82 PHE
LEU 75 ILE ASN 76 HIS ILE 79 MET LEU 82 HIS
LEU 15 ILE ASN 76 HIS ILE 79 MET LEU 82 TYR . . ?
LEU 75 ILE ASN 76 HIS ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 THR LEU 82 TYR •LEU 75 ILE ASN 76 HIS ILE 79 VAL LEU 82 PHE
LEU 75 ILE ASN 76 HIS ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS ILE .79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 MET LEU 82 TYR LEU 75 MET ASN 76 HIS ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 THR LEU 82 TYR LEU 75 MET ASN 76 HIS ILE 79 VAL LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS ILE 79 LEU LEU 82 PHE LEU 75 VAL ASN 76 HIS ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS ILE 79 MET LEU 82 PHE LEU 75 VAL ASN 76 HIS ILE 79 MET LEU 82 HIS . LEU 75 VAL ASN 76 HIS ILE 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS ILE 79 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS ILÉ 79 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS ILE 79 THR LEU 82 TYR ' LEU 75 VAL ASN 76 HIS ILE 79 VAL LEU 82 PHE * ‘
LEU 75 VAL ASN 76 HIS ILE 79 VAL LEU 82 HIS,
LEU 75 VAL ASN 76 HIS ILE 79 VAL LEU 82 TYR LEU 75 ILE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 75 ILE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 75 ILE ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 75 MET ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 75 MET ASN 76 HIS ILE 79 MET VAL 81 THR LEU 75 MET ASN 76 HIS ILE 79 THR VAL 81 THR LEU 75 MET ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 75 VAL ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 75 VAL ASN 76 HIS ILE 79 MET VAL 81 THR LEU 75 VAL ASN 76 HIS ILE 79 THR VAL 81 THR LEU 75 VAL ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASN LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN LEU 82 HIS
LEU 75 ILE ASN 76 HIS SER 78 GLN LEU 82 TYR
LEU 75 ILE ASN 76 HIS SER 78 HIS LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 HIS LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR LEU 82 TYR
LEU 75 MET ASN 76 HIS SER 78 ASN LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN LEU 82 TYR LEU 75 MET ASN 76HISSER 78 HIS LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 LYS LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ARG LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 TYR LEU 82 PHE
LEU 75 VAL ASN 76 HIS SER 78 TYR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASN VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 THR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ARG VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASP VAL 81 THR ; LEU 75 ILE ASN 76 HIS SER 78 GLN VAL 81 THR
LEU 75 ILE ASN 76 HIS SER 78 HIS VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 LYS VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 TYR VAL 81 THR ! LEU 75 MET ASN 76 HIS SER 78 ASN VAL 81 THR
LEU 75 MET ASN 76 HIS SER 78 THR VAL'81 THR ; LEU 75 MET ASN 76 HIS SER 78 ARG VAL 81 THR ' LEU 75 MET ASN 76 HIS SER 78 ASP VAL 81 THR
LEU 75 MET ASN 76 HIS SER 78 GLN VAL 81 THR • LEU 75 MET ASN 76 HIS SER 78 HIS VAL 81 THR
LEU 75 MET ASN 76 HIS SER 78 LYS VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 TYR VAL 81 THR LEU 75 VAL ASN 76 HIS SER 78 ASN VAL 81 THR LEU 75 VAL ASN 76 HIS SER. 78 THR VAL 81 THR LEU 75 VAL ASN 76 HIS SER 78 ARG VAL 81 THR LEU 75 VAL ASN 76 HIS ŠER 78 ASP VAL 81 THR LEU 75 VAL ASN 76 HIS SER 78 GLN VAL 81 THR LEU 75 VAL ASN 76 HIS SER 78 HIS VAL 81 THR LEU 75 VAL ASN 76 HIS SER. 78 LYS VAL 81 THR LEU 75 VÁL ASN 76 HIS SER 78 TYR VAL 81 .THR
LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 75 ILE ASN 76 HIS SÉR 78 ASN ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 VAL LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 MET LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 THR Λ LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 VAL
LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 MET LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 MET LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 MET LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 MET LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 MET
| • | • | • 44 | ·· |
| • | 4 | 4 · | • · · |
| • | • | 4 · | • · · |
| • · · | 4 4· | 4 4· · ··· | • · |
LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 75 MET ASN 76 HIS SER 78THRILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 THRILE 79 THR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 VAL LEU 75 MET ASN 76 HISSER 78 ARG ILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 THR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 THR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 THR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 75 MET. ASN 76 HIS SER 78 HIS ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 THR LEU 75 MET ASN 76 HIS SÉR 78 HIS ILÉ 79 VAL LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 THR LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 THR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 MET LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 THR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 LEU LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 MET LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 THR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 VAL LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 MET LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 THR LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 MET LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 THR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 MET LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 THR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 MET • ♦ ♦ • · · • ' · • · • · • ·· •' ·
LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 THR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 MET LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 THR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 MET LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 THR LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 VAL
Tabulka 6
Pětinásobné substituční varianty
ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU .82 PHE . ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 HIS ' ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 TYR .. ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE . ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 THR ILE 79 MET VAL81 THR LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 8 Γ THR LEU 82 PHE ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82PHÉ *' ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 HIS
9 9 99 99 99
9 ·· 99 9 9. 9 9 9 9
9 9 ·>···· • · · · ··· · · ·'
9 9 9 9 9 9 9
999 999 999 9999 99 99
ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 HIS ' ASN 76 HIS SER 78 ASP ILE 79 VAL VAL,.81 TOR LEU 82 TYR ASN 76 HIS SER 78 GLN ILE 79 LEU VAL . 81 THR LEU 82 PHE ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 TOR LEU 82 TYR ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 TOR LEU. 82 PHE ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 TOR LEU 82 PHE ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 GLN ILE 79 TOR VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 TOR LEU 82 HIS ASN 76 HIS SÉR 78 GLN ILE 79 VAL VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 TOR LEU 82 TYR ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 TOR LEU 82 TYR , ASN 76 HIS SER 78 HIS ILE 79 THR V AL 81 THR LEU 82 PHE . * ASN 76 HIS SER 78 HIS ILE 79 TOR VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 HIS ILE 79.TOR VAL 81 TOR LEU 82 TYR ' ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 TOR LEU 82 TYR ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 TOR LEU 82 PHE ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 TOR LEU 82 PHE ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 LYS ILE 79 TOR VAL 81 TOR LEU 82 PHE ASN 76 HIS SER 78 LYS ILE 79 TOR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 TOR LEU 82 TYR ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 TOR LEU 82 PHE ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 TOR LEU 82 TYR ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 TOR LEU 82 PHE ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 TOR LEU 82 TYR ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 TOR LEU 82 PHE ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 TYR ILE 79 TOR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 TYR ILE 79 TOR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 TYR ILE 79 TOR VAL 81 THR LEU 82 TYR ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 TOR LEU 82 PHE ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 TOR LEU 82 HIS ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE ♦ · » ·· ·· • · • · • , · ·«· ··· »· ·· • 4 « · « · • · · · • · · · « • · · · • · 9 9
LEU 75 ILE SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 MET VAL 81 THR LEU. 82 TYR LEU 75 ILE SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 THR VAL 81THR LEU 82 TYR LEU 75 ILE SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 VAL VAL 81THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ARG ILE 79 LEU VAL 8 , THR LEU 82 TYR . LEU 75 ILE SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ARG ILE *79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ARG ILE 79 THR VAL· 81 THR LEU 82 HIS LEU 75 ILE SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 TYR
LEU 75 ILE SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 TYR
LEU 75 MET SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 THR VAL 811HRLEU 82 TYR LEU 75 MET SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 THR ILE 79 MET VÁL 81 THR LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS
LEU 75 MET SER 78 THR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET SER . 78 ASP ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET SER 78ÁSPILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 HIS ILE 79 TOR VAL 81 TOR LEU 82 TYR LEU 75 MET SER 78 HIS ILE 79 VAL VAL 81 TOR LEU 82 PHE LEU 75 MET SER 78 HIS ILE 79 VAL VAL 81 TOR LEU 82 HIS LEU 75 MET SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 LYS ILE 79 LEU VAL 81 TOR LEU 82 PHE
LEU 75 MET SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 LYS ÍLE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 LYS ILE 79 VAL VAL 81 THR.LEU 82 PHE LEU 75 MET SER 78 LYS ILE 79 VAL VAL 81 THRLEU 82 HIS LEU 75 MET SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 THR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 THR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 TYR » ’ · .· · ·
- i ·>/··-' · · * >'- ··'· · v-·· · · ·' 9 9 · . ' · . *ř · · · - · · · ·
·. *· .· · · ······· -·· . 99
LEU 75 VAL SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ASP ILE 79 MET VAL 81.THR LEU 82 PHE LEU 75 VAL SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 GLN ILE 79 THR VAL .81. THR LEU 82 TYR LEU 75 VAL SER 78 GLN ILE 79 VAL VAL 81 THRLEU 82 PHE LEU 75 VAL SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 HIS
LEU 75 VAL SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE
LEU 75 ILE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS ILE 79 MEŤ VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS ILE 79 THR VAL 81THRLEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR VAL 81THRLEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 PHE
-Λχ·
LEU 75 ILE ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 PHE
LEU 75 ILE ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 TYR
LEU 75 MET ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR VAL 81'THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR VAL 81THRLEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ARG VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS VAL 81 THR LEU 82 TYR
LEU 75 VAL ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 PHE
LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 HIS
LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 7? THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SÉR 78 ASN ILE 79 VAL LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 HIS LEU 75ILEASN 76HISSER 78 THR ILE 79 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 TYR4 LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 HIS
Tj'-1* • ·
LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SER ,78 HIS ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SEŘ 78 LYS ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 PHE
LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 HIS LEU 75 MET-ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 TYR LEU ,75 MET ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 TYR • Β ·<
·· • ' · · · · • .· · . » · · • - · ·. · · · • * · 4 ·
LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 TYR LEU—75MET-ASN-76TIIS SER 78 LYS ILE79VALLEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 HIS LEU 75METASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG ILĚ 79 MET LEU 82 PHE LEU 75-VAL ASN 76 HIS SER 78 ARG ILE-79 MET LEU 82 HIS ·*· ··« ««· ···· ·' · <1 * · · · • · · * ·' ·· . ··
LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 TOR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 VAL LEU82HIS LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 METLEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 TOR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 TOR LEU .82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 MET LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN ILE , 79 MET LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN ILÉ 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 TOR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 TOR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 TOR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 TOR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS ILÉ 79 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 VAL LEU 82 TYR LEU 75 VAL ASN 76 HIS SÉR 78 TYR ILE 79 LEU LEU 82 PHE ?·
LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 LEU LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 MET LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 TOR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 TOR LEU 82.TYR LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 VAL LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR ILE ,79 VAL LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 ŤHR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 TOR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR > LEU 75 ILE ASN 76 HIS SER 78 TOR ILE 79 LEU VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 TOR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 75ILÉASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 TOR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 ASPILE 79 MET VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 TOR VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 TOR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 TOR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 TOR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 TOR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 TOR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 75 MET ASN 76HISSER 78 ASN ILE 79 LEU VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 TOR VAL 81 TOR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 TOR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 TOR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 TOR LEU 75 MET ASN 76 HIS SER 78 TOR ILE 79 TOR VAL 81 TOR LEU 75 MET ASN 76 HIS SER 78 TOR ILE 79 VAL VAL 81 TOR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 75 MET ASN 76H1SSER 78 ARG ILE 79 THR VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 75 MEŤ ASN 76 HIS SER 78 ASPILE 79 LEU VAL 81 THR
LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR
LEU 75MET ASN 76 HIS SER
LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 MET ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER LEU 75 VAL ASN 76 HIS SER
GLN ILE 79 VAL VAL 81 THR
HIS ILE 79 LEU VAL 81 THR 78 HIS ILE 79 MET VAL 81 THR 78 HIS ILE 79 THR VAL 81 THR 78 HIS ILE 79 VAL VAL 81 THR 78 LYS ILE 79 LEU VAL 81 THR 78 LYS ILE 79 MET VAL 81 THR 78 LYS ILE 79 THR VAL 81 THR 78 LYS ILE 79 VAL VAL 81 THR 78 TYR ILE 79 LEU VAL 81 THR 78 TYR ILE 79 MET VAL 81 THR 78 TYR ILE 79 THR VAL 81 THR 78 TYR ILE 79 VAL VAL 81 THR 78 ASN ILE 79 LEU VAL 81 THR 78 ASN ILE 79 MET VAL 81 THR 78 ASN ILE 79 THR VAL 81 THR 78 ASN ILE 79 VAL VAL 81 THR 78 THR ILE 79 LEU VAL 81 THR 78 THR ILE 79 MET VAL 81 THR 78 THR ILE 79 THR VAL 81 THR 78 THR ILE 79 VAL VAL 81 THR 78 ARG ILE 79 LEU VAL 81 THR 78 ARG ILE 79 MET VAL 81 THR 78 ARG ILE 79 THR VAL 81 THR 78 ARG ILE 79 VAL VAL 81 THR 78 ASP ILE 79 LEU VAL 81 THR 78 ASP ILE 79 MET VAL 81 THR 78 ASP ILE 79 THR VAL 81 THR 78 ASP ILE 79 VAL VAL 81 THR 78 GLN ILE 79 LEU VAL 81 THR 78 GLN ILE 79 MET VAL 81 THR 78 GLN ILE 79 THR VAL 81 THR 78 GLN ILE 79 VAL VAL 81 THR 78 HIS ILE 79 LEU VAL 81 THR 78 HIS ILE 79 MET VAL 81 THR 78 HIS ILE 79 THR VAL 81 THR 78 HIS ILE 79 VAL VAL 81 THR 78 LYS ILE 79 LEU VAL 81 THR 78 LYS ILE 79 MET VAL 81 THR 78 LYS ILE 79 THR VAL 81 THR 78 LYS ILE 79 VAL VAL 81 THR 78 TYR ILE 79 LEU VAL 81 THR 78 TYR ILE 79 MET VAL 81 THR 78 TYR ILE 79 THR VAL 81 THR 78 TYR ILE 79 VAL VAL 81 THR
Tabulka 7
Šestinásobné substituční varianty
LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75ILE ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79THR VAL 81THRLEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81THRLEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 HIS
LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS
------ LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR
LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 TYR
LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE • · · · · « ·
LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 PHE , > LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 THR VAL «81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75.MET ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81THRLEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE
LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR * ·
LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 TYR LÉU 75 MET ASN 76 HIS SER 78 LYS ILE 79 THR VÁL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 THR ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 HIS • ·
LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ARG ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79.MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 ASP ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 LEU VAL 81THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS ŠER 78GLNILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 GLN ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE
LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 HIS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 THR VAL 81THRLEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 LYS ILE 79 VAL VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 LEU VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 PHE
LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 MET VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 THR VAL 81 THR LEU 82 TYR LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 PHE LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 HIS LEU 75 VAL ASN 76 HIS SER 78 TYR ILE 79 VAL VAL 81 THR LEU 82 TYR
Tabulka 8
Jednoduché,substituční varianty
LEU 82 PHE LEU 82 HIS VAL 81 THR ILE 79 LEU ILE 79 MET ILE 79 THR SER 78 ASN SER 78 THR ASN 76 HIS LEU 75 ILE LEU 75 MET
Tabulka 9
Dvojité substituční varianty
VAL 81 THR LEU 82 PHE VAL 81 THR LEU 82 HIS ILE 79 LEU LEU 82 PHE ILE 79 LEU LEU 82 HIS ILE 79 MET LEU 82 PHE ILE 79 MET LEU 82 HIS ILE 79 THR LEU 82 PHE ILE 79 THR LEU 82 HIS ILE 79 LEU VAL 81 THR ILE 79 MET VAL 81 THR ILE 79 THR VAL 81 THR SER 78 ASN LEU 82 PHE SER 78 ASN LEU 82 HIS SER 78 THR LEU 82 PHE SER 78 THR LEU 82 HIS SER 78 ASN VAL 81 THR SER 78 THR VAL 81 THR SER 78 ASN ILE 79 LEU SER 78 ASN ILE 79 MET SER 78 ASN ILE 79 THR SER 78 THR ILE 79 LEU SER 78 THR ILE 79 MET SER 78 THR ILE 79 THR ASN 76 HIS LEU 82 PHE ASN 76 HIS LEU 82 HIS ASN 76 HIS VAL 81 THR ASN 76 HIS ILE 79 LEU
• ·
ASN 76 HIS ILE 79 MET ASN 76 HIS ILE 79 THR ASN 76 HIS SER 78 ASN ASN 76 HIS SER 78 THR LEU 75 ILE LEU 82 PHE LEU 75 ILE LEU 82 HIS LEU 75 MET LEU 82 PHE LEU 75 MET LEU 82 HIS LEU 75 ILE VAL 81 THR LEU 75 MET VAL 81 THR LEU 75 ILE ILE 79 LEU LEU 75 ILE ILE 79 MET LEU 75 ILE ILE 79 THR LEU 75 MET ILE 79 LEU LEU 75 MET ILE 79 MET LEU 75 MET ILE 79 THR LEU 75 ILE SER 78 ASN LEU 75 ILE SER 78 THR LEU 75 MET SER 78 ASN LEU 75 MET SER 78 THR LEU 75 ILE ASN 76 HIS LEU 75 MET ASN 76 HIS
Tabulka 10
Trojnásobné substituční varianty
ILE 79 LEU VAL 81 THR LEU 82 PHE ILE 79 LEU VAL 81 THR LEU 82 HIS ILE 79 MET VAL 81 THR LEU 82 PHE ILE 79 MET VAL 81 THR LEU 82 HIS ILE 79 THR VAL 81 THR LEU 82 PHE ILE 79 THR VAL 81THRLEU 82 HIS SER 78 ASN VAL 81THRLEU 82 PHE SER 78 ASN VAL 81 THR LEU 82 HIS SER 78 THR VAL 81THRLEU 82 PHE SER 78 THR VAL 81THRLEU 82 HIS SER 78 ASN ILE 79 LEU LEU 82 PHE SER 78 ASN ILE 79 LEU LEU 82 HIS SER 78 ASN ILE 79 MET LEU 82 PHE SER 78 ASN ILE 79 MET LEU 82 HIS SER 78 ASN ILE 79 THR LEU 82 PHE SER 78 ASN ILE 79 THR LEU 82 HIS SER 78 THR ILE 79 LEU LEU 82 PHE SER 78 THR ILE 79 LEU LEU 82 HIS SER 78 THR ILE 79 MET LEU 82 PHE SER 78 THR ILE 79 MET LEU 82 HIS SER 78 THR ILE 79 THR LEU 82 PHE SER 78 THR ILE 79 THR LEU 82 HIS SER 78 ASN ILE 79 LEU VAL 81 THR SER 78 ASN ILE 79 MET VAL 81 THR SER 78 ASN ILE 79 THR VAL 81 THR SER 78 THR ILE 79 LEU VAL 81 THR SER 78 THR ILE 79 MET VAL 81 THR SER 78 THR ILE 79 THR VAL 81 THR ASN 76 HIS VAL 81 THR LEU 82 PHE * · · • ·
ASN 76 HIS VAL 81 THR LEU 82 HIS ASN 76 HIS ILE 79 LEU LEU 82 PHE ASN 76 HIS ILE 79 LEU LEU 82 HIS ASN 76 HIS ILE 79 MET LEU 82 PHE ASN 76 HIS ILE 79 MET LEU 82 HIS ASN 76 HIS ILE 79 THR LEU 82 PHE
------- ASN 76 HIS ILE 79 THR LEU 82 HIS ? ASN 76 HIS ILE 79 LEU VAL 81 THR
ASN 76 HIS ILE 79 MET VAL 81 THR ASN 76 HIS ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 ASN LEU 82 PHE ASN 76 HIS SER 78 ASN LEU 82 HIS ; ASN 76 HIS SER 78 THR LEU 82 PHE , ASN 76 HIS SER 78 THR LEU 82 HIS
ASN 76 HIS SER 78 ASN VAL 81 THR ASN 76 HIS SER 78 THR VAL 81 THR ASN 76 HIS SER 78 ASN ILE 79 LEU ASN 76 HIS SER 78 ASN ILE 79 MET ASN 76 HIS SER 78 ASN ILE 79 THR ASN 76 HIS SER 78 THR ILE 79 LEU ASN 76 HIS SER 78 THR ILE 79 MET ASN 76 HIS SER 78 THR ILE 79 THR LEU 75 ILE VAL 81 THR LEU 82 PHE LEU 75 ILE VAL 81 THR LEU 82 HIS LEU 75 MET VAL 81 THR LEU 82 PHE LEU 75 MET VAL 81THRLEU 82 HIS LEU 75 ILE ILE 79 LEU LEU 82 PHE LEU 75 ILE ILE 79 LEU LEU 82 HIS LEU 75 ILE ILE 79 MET LEU 82 PHE LEU 75 ILE ILE 79 MET LEU 82 HIS LEU 75 ILE ILE 79 THR LEU 82 PHE LEU 75 ILE ILE 79 THR LEU 82 HIS LEU 75 MET ILE 79 LEU LEU 82 PHE LEU 75 MET ILE 79 LEU LEU 82 HIS > LEU 75 MET ILE 79 MET LEU 82 PHE
LEU 75 MET ILE 79 MET LEU 82 HIS LEU 75 MET ILE 79 THR LEU 82 PHE , LEU 75 MET ILE 79 THR LEU 82 HIS e LEU 75 ILE ILE 79 LEU VAL 81 THR
- LEU 75 ILE ILE 79 MET VAL 81 THR
LEU 75 ILE ILE 79 THR VAL 81 THR ‘ ’ LEU 75 MET ILE 79 LEU VAL 81 THR » LEU 75 MET ILE 79 MET VAL 81 THR
LEU 75 MET ILE 79 THR VAL 81 THR ’ LEU 75 ILE SER 78 ASN LEU 82 PHE
LEU 75 ILE SER 78 ASN LEU 82 HIS LEU 75 ILE SER 78 THR LEU 82 PHE LEU 75 ILE SER 78 THR LEU 82 HIS LEU 75 MET SER 78 ASN LEU 82 PHE LEU 75 MET SER 78 ASN LEU 82 HIS LEU 75 MET SER 78 THR LEU 82 PHE LEU 75 MET SER 78 THR LEU 82 HIS LEU 75 ILE SER 78 ASN VAL 81 THR LEU 75 ILE SER 78 THR VAL 81 THR
LEU 75 MET SER 78 ASN VAL 81 THR * LEU 75 MET SER 78 THR VAL 81 THR
L r
ř' -
LEU 75 ILE SER 78 ASN ILE 79 LEU LEU 75 ILE SER 78 ASN ILE 79 MET LEU 75 ILE SER 78 ASN ILE 79 THR LEU 75 ILE SER 78 THR ILE 79 LEU LEU 75 ILE SER 78 THR ILE 79 MĚT LEU 75 ILE SER 78 THR ILE 79 THR LEU 75 MET SER 78 ASN ILE 79 LEU LEU 75 MET SER 78 ASN ILE 79 MET LEU 75 MET SER 78 ASN ILE 79 THR LEU 75 MET SER 78 THR ILE 79 LEU LEU 75 MET SER 78 THR ILE 79 MET LEU 75 MET SER 78 THR ILE 79 THR LEU 75 ILE ASN 76 HIS LEU 82 PHE LEU 75 ILE ASN 76 HIS LEU 82 HIS LEU 75 MET ASN 76 HIS LEU 82 PHE LEU 75 MET ASN 76 HIS LEU 82 HIS LEU 75 ILE ASN 76 HIS VAL 81 THR LEU 75 MET ASN 76 HIS VAL 81 THR LEU 75 ILE ASN 76 HIS ILE 79 LEU LEU 75 ILE ASN 76 HIS ILE 79 MET LEU 75 ILE ASN 76 HIS ILE 79 THR LEU 75 MET ASN 76 HIS ILE 79 LEU LEU 75 MET ASN 76 HIS ILE 79 MET LEU 75 MET ASN 76 HIS ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 ASN LEU 75 ILE ASN 76 HIS SER 78 THR LEU 75 MET ASN 76 HIS SER 78 ASN LEU 75 MET ASN 76 HIS SER 78 THR
Tabulka 11 čtyřnásobné substituční varianty
SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 PHE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 HIS ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 PHE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 PHE ··
ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 HIS
ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 75 ILE ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ILE 79 LEU VAL 81 THR LEU 82 HIS
LEU 75 MET ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 LEU LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 MET LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 LEU LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 MET LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 LEU LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 LEU LEU 82 PHE
LEU 75 MET SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 MET LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 THR LEU 82,PHE LEU 75 MET SER 78 THR ILE 79 THR LEU 82 HIS LEU 75 ILE SER 78 ÁSN ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 ILE SER 78 ASN ILE 79 THR VAL 81 THR LEU 75 ILE SER 78 THR ILE 79 LEU VAL 81 THR LEU 75 ILE SER 78 THR ILE 79 MET VAL 81 THR LEU 75 ILE SER 78 THR ILE 79 THR VAL 81 THR LEU 75 MET SER 78 ASN ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 MET SER 78 ASN ILE 79 THR VAL 81 THR LEU 75 MET SER 78 THR ILE 79 LEU VAL 81 THR LEU 75 MET SER 78 THR ILE 79 MET VAL 81 THR LEU 75 MET SER 78 THR ILE 79 THR VAL 81 THR LEU 75 ILE ASN 76 HIS VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS VAL 81 THR LEU 82 HIS
LEU 75 ILE ASN 76 HIS ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 75 ILE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 75 MET ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 75 MET ASN 76 HIS ILE 79 MET VAL 81 THR LEU 75 MET ASN 76 HIS ILE 79 THR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASN LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 THR VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ASN VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 THR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 THR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET
s.
LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR
LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR
Tabulka 12
Pětinásobné substituční varianty
ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 LEU VAL 81 THR LEU 82 HIS
• ····
LEU 75 MET ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75ILEASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 HI$
LEU 75 ILE ASN 76 HIS ŠER 78 THR VÁL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET LÉU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS ŠER 78 ASN ILE 79 LEU VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR
Tabulka 13
Šestinásobné substituční varianty
LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE • · « · • · • · · · · ·
LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASŇ 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS ŠER 78 THR ILE 79 MET VÁL 81 THR LEU 82 HIS LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 ILE ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEÚ 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 LEU VAL 81.THR LEU 82 PHE LEU 75 MET ASN 76HISSER 78 ASN ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 ASN ILE 79 THR VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 LEU VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 MET VAL 81 THR LEU 82 HIS LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 PHE LEU 75 MET ASN 76 HIS SER 78 THR ILE 79 THR VAL 81 THR LEU 82 HIS
Vně epitopové oblasti může být vytvořena jedna nebo více dalších substitučních mutací („stabilizující mutace“), aby se například proteáza znovu stabilizovala po mutacích, provedených v epitopové oblasti, nebo aby se zvýšila proteolytické aktivita varianty. Mnoho takových stabilizujících mutací je v oboru známo. Příklady takových stabilizujících mutací jsou uvedeny například vWO 95/10591, Baeck a kol., publikovaný 20. dubna 1995; patentu US č. 4 914 031, Zukowski a kol., vydaný 3. dubna 1990; patentu US č. 5 470 733, Bryan a kol., vydaný 22. října 1996; WO 89/07642, patentu US č. 5 707 848, Bryan a kol., vydaný 13. ledna 1998; Van Eekelen a kol., publikovaný 24. srpna 1989; WO 87/04461, Stabinski a kol., publikovaný 30. července 1987; patent US č. 4 760 025, Estell a kol., vydaný 26. července 1988; WO 92/11348, Branner a kol., publikovaný 9. července 1992; EP 0 405 901, Casteleijn a kol., publikovaný 2. ledna 1991; WO 91/00345, Branner a kol., publikovaný 10. ledna 1991 a WO 94/10020, Brode a kol., publikovaný 23. března 1995.
Výhodnými stabilizujícími mutacemi jsou jedna nebo více zdáte uvedených: I107V; K213R; Y217L; Y217K; N218S; G169A; M50F; Q19E; P5A; S9A; I31L; E156S; G169A; N212G; S188P; T254A; S3C + Q206C a Q271E. Výhodnějšími stabilizujícími mutacemi jsou jedna nebo více z dále uvedených: P5A; S9A, 131L, E156S, G169A,
N212G; S188P; T254A; S3C + Q206C; Q271E; Y217L a Y217K. Nejvýhodnějšími stabilizujícími mutacemi jsou Y217L a Y217K.
Výhodná varianta pro použití v prostředcích pro osobní hygienu je Δ 75 - 83, Y217L.
Způsoby přípravy.
Varianty jsou připraveny pomocí mutování nukleotidových sekvencí, které kódují standardní serinovou proteázu, čímž vznikají varianty s modifikovanými aminokyselinovými sekvencemi. Takové metody jsou v oboru dobře známé, jedna taková metoda je uvedená dále:
Fágemid (pSS-5), obsahující gen pro standardní subtilizin BPN' (Mitchison, C. a J.A. Wells, „Protein Engineering of Disulfide Bonds in Subtilisin BPN'“, Biochemistry, sv. 28, str. 4807 až 4815 (1989) je transformován do kmene CJ236 Escherichia coli dutung- a jednovláknová DNA matrice obsahující uráčil je vytvořena pomocí VCSM13 helper fága (Kunkel a kol., „Rapid and Efficient Site-Specific Mutagenesis Without Phenotypic Selection“, Methods in Enzymology, sv. 154, str. 367 až 82 (1987), postupem modifikovaným podle Yuckenberg a kol., „Site-Directed in vitro Mutagenesis Using Uracil-Containing DNA and Phagemid Vectors“, Directěd Mutagenesis -A Practical Approach, McPherson, M. J. ed., str. 27 až 48 (1991). Místně cílená mutageneze pomocí primerů, odvozená z metody Zoller a Smith (Zoller, M. J. a M. Smith, „Oligonucleotide - Directed Mutagenesis Using M13 - Derived Vectors: An Efficient and General Proceduře of Point Mutations in any Fragment of DNA“, Nucleic Acids Research, sv. 10, str. 6487 až 6500 (1982), je použita pro přípravu všech mutant (v podstatě jak je uvedeno v Yuckenberg a kol., „Site-Directed in vitro Mutagenesis Using Uracil-Containing DNA and Phagemid Vectors“, Directed Mutagenesis - A Practical approach, McPherson, M. J. ed., str. 27 až 48 (1991)).
Oligonukleotidy jsou připraveny pomocí DNA syntetizátoru 380B (Applied Biosystems lne.). Produkty mutačních reakcí jsou transformovány do Escherichia coli kmene MM294 (Americká sbírka typových kultur E. coli 33625). Všechny mutace jsou potvrzeny pomocí sekvenování DNA a izolovaná DNA je transformována do expresního kmene PG632 Bacillus subtilis (Saunders a kol., „Optimization of the Signal-Sequence Cleavage Site for Secretion from Bacillus subtilis of a 34-amino acid Fragment of Human Parathyroid Hormone“, Gene, sv. 102, str. 277 až 282 (1991) a Yang a kol., „Cloning of the Neutrál Protease Gene of Bacillus subtilis and the Use of the Cloned ·· ···· • · • · ·· ·· ·· ·· • · · · · φ • · · · · ·
Gene to Create an in vitro - Derived Deletion Mutation“, Journal of Bacteriology, sv. 160, str. 15 až 21 (1984). Aktivita varianty je předběžně určována podle schopnosti buněk PG632, transformovaných mutantou plazmidy, hydrolysovat kasein.
Fermentace je následující. Buňky Bacillus subtilis (PG632), obsahující studovanou variantu rostou do střední logaritmické fáze v jednom litru LB bujónu, obsahujícího glukózu 10 g/litr, naočkovány do fermentoru Biostat C (Braun Biotech, lne., Allentown, PA) v celkovém objemu 9 litrů. Fermentační médium obsahuje kvasničný výtažek, kaseinový hydrolyzát, rozpustný - částečně hydrolyzovaný škrob (Maltrin M-250), činidla zamezující tvorbě pěny, pufry a stopové minerály (viz „Biology ζ 't of Bacilli: Application to Industry“, Doi* R. H. a M. McGloughin, ed. (1992)). Bujón je ; udržován během fermentačního cyklu při konstantním pH 7,5. Pro antibiotikovou ΐ*; selekci mutovaných plazmidů je přidán kanamycin (50 pg/ml). Buňky jsou pěstovány po • dobu 18 hodin při teplotě 37 °C do A®» asi 60 a výtěžek je potom odebrán.
> Aby byla získána čistá varianta, je fermentační bujón je zpracován pomocí / následujících kroků. Bujón je zbaven buněk Bacillus subtilis průchodem přes 0,16 pm membránu. Bezbuněčný bujón je potom koncentrován ultrafiltrací přes membránu, která zadržuje molekuly s molekulovou hmotností 8000. pH je upraveno na 5,5 pomocí koncentrovaného pufru MES (2-(N-morfolin)ethanolsulfonová kyselina). Varianta je dále čištěna pomocí iontoměničové chromatografie (výměna kationtů) na S-sepharoze a elucí pomocí gradientů NaCl. (Viz Scopes, R. K., „Protein Purification Principles and Practice“, Springer-Verlag, New York (1984).
„ Pro určení koncentrace aktivní varianty ve frakcích sebraných v průběhu gradientově eluce je použit test pNA (DelMar a kol., Analytical Biochemistry, sv. 99, str. 316 až 320 (1979)). Tento test měří rychlost s jakou je uvolňován p-nitroanilin, když
13* varianta hydrolyzuje rozpustný syntetický substrát, sukcinyl-alanin-alanin-prolin' fenylalanin-p-nitroanilln (sAAPF-pNA). Rychlost s jakou hydrolyzační reakce vytváří žlutou barvu je měřena při 410 nm na spektrofotometru a je úměrná koncentraci aktivního enzymu. Dále je použito měření absorbance při 280 nm pro určení celkové koncentrace proteinů. Poměr aktivní enzym/celkový protein udává čistotu varianty a je používán pro určování frakcí, které budou spojeny pro přípravu zásobního roztoku.
Aby bylo zabráněno autolýze varianty během skladování, je ke spojeným frakcím, získaným z chromatografického sloupce, přidána stejná hmotnost propylenglykolu. Po skončení purifikačního postupu je čistota zásobního roztoku
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..... ·..··..· varianty kontrolována SDS-PAGE (poiyakrylamidová eiektroforéza v přítomnosti sodium dodecylsulfátu) a absolutní koncentrace enzymu je určována pomocí metody titrace aktivního místa za použití trypsinového inhibitoru typu ll-T: krocaní bflek (Sigma Chemical Company, St. Louis, MO).
Při přípravě pro použití je zásobní roztok enzymu vyčištěn na sloupci SephadexG25 (Pharmacia, Piscataway, New Jersey), aby byl odstraněn propylengíykol a vyměněn pufr. Pufr MES, přítomný v zásobním roztoku enzymu je zaměněn za pufr 0,1 M tris (tris(hydroxymethylaminomethan)), obsahující 0,01 M CaCi2 a pH je upraveno na
8,6 pomocí HCI. Všechny pokusy jsou provedeny při pH 8,6 vtrisovém pufru, temperovaném na 25 °C.
Analytické metody.
U variant, které jsou předmětem tohoto vynálezu, může být pomoci následujících metod testována jejich enzymatická aktivita a imunitní a/nebo alergická odpověď, obě jsou známy osobám se zkušenostmi v oboru. Popřípadě mohou být použity jiné, v oboru dobře známé metody.
Aktivita varianty.
Proteázová aktivita varianty, která jé předmětem tohoto vynálezu, může být testována pomocí metod, které jsou v oboru dobře známé. Dvě takové metody jsou představeny dále:
Aktivita měřená na šupinkách kůže.
Pomocí pásky Scotch® #3750, jsou opakovaně z nohou subjektu sloupávány šupinky kůže tak dlouho, dokud není páska od těchto šupinek dosti matná. Páska je potom rozstříhána na čtverce o rozměrech 1 palec na 1 palec a uložena. Do petriho misky o rozměrech 10 mm krát 35 mm je v pufru 0,01 M KH2PO4 pH 5,5 přidáno 0,75 mg/ml kontrolního enzymu (například subtilizin BPN ) nebo varianta, která bude testována. K tomuto roztoku je přidán 1 ml 2,5% laurátu sodného pH 8,6. Roztok je mírně míchán na deskovém míchadle. Předem připravený čtverec pásky je ponechán nasát v tomto roztoku (stranou s šupinkami kůže nahoru) po dobu 10 min. za pokračujícího mírného míchání. Čtverec pásky je potom opláchnut vodovodní vodou po dobu 15 s. Do čisté petriho misky jsou napipetovány 3 ml modré barvy Stevenel Blue (3ml, komerčně dostupná od Sigma Chemical Company, St. Louis, MO). Opláchnutý čtverec pásky je umístěn na tři minuty do barvy (stranou s šupinkami kůže nahoru) za mírného míchání. Čtverec pásky je z barvy vyjmut a postupně opláchnut ve dvou 300 ·· ϊ·*· .ϊ *· ·· ·· • · · ···· · · · • ··· ♦ . · , „ , · τ— . - · ·* ···*··»»
·.,··..· ml kádinkách s destilovanou vadou, každé opláchnutí trvalo 15 sekund. Poté byl čtverec pásky ponechán na vzduchu uschnout. Intenzita barvy čtverce pásky, získaná v kontrolním enzymu a intenzita barvy čtverce pásky, získaná ve variantě, jsou porovnány vizuálně nebo pomocí chromometru. Čtverec pásky z varianty s menší intenzitou barvy vzhledem ke čtverci pásky z kontrolního enzymu, prokazuje variantu, která má vyšší aktivitu.
Aktivita měřená pomocí zbarvení kolagenu.
K 50 ml 0,1 M tris pufru (tris(hydroxymethylaminomethan)), obsahujícího 0,01 M CaCI2 s pH 8,6 je přidáno 0,5 g azocoll (kolagen napuštěný azobarvivem, komerčně dostupný od Sigma Chemical Company, St. Louis, MO). Směs je inkubována při 25 °C za mírného míchání na deskové míchačce. Dva mililitry této směsi je přefiltrováno přes injekční filtr 0,2 mikronu a změřena jeho absorbance při 520 nm a na tuto hodnotu je nastavena nula spektrfotometru. Pak je ke zbývajícím 48 ml směsi tris/azocoll přidána 1 ppm kontrolního enzymu (například subtilizin BPN ) nebo testované varianty. Každé 2 min. jsou přefiltrovány 2 ml roztoku, obsahujícího kontrolu či variantu, přes injekční filtr 0,2 mikronu. U každého filtrovaného vzorku je ihned změřena jeho absorbance při 520 nm a výsledky jsou vyneseny v závislostí na čase. Sklony křivek kontroly a testovaného konjugátu jsou známkou relativních aktivit vzorků. Vyšší sklon křivky je známkou vyšší aktivity. Test aktivity varianty (sklon) může být vyjádřen v procentech aktivity kontroly (sklonu).
Test množení T-buněk.
Imunologický a/nebo alergický potenciál variant, které jsou předmětem tohoto vynálezu, může být určen pomocí testu množení T-buněk, který je zde dále uvedený. Tento test je variantou testu popsaného v Bungy Poor Fard a kol., „T Cell Epitopes og the Major Fraction of Rye Grass Lolium perenne (Lol ρ I) Defined Usibg Overlpping Peptides in vitro and in vivo“, Clinical Experimental Immunology, sv. 94, str. 111 až 116 (1993).
V tomto testu jsou použity krve osoby alergické k subtilizinu BPN' (pozitivní kožní test) a osoby kontrolní (negativní kožní test). Od každé osoby je odebráno asi 60 ml krve, ze které jsou pomocí ficoll-hypaque (který může být získán od Pharmacia, Piscataway, New Jersey), získány mononukíeární buňky. Buňky jsou promyty dvakrát v RPMI 1640 (které může být získáno od Gibco, Grand Island, New York) a potom resuspendovány v kompletním médiu RPM11640, doplněném 10 % lidského AB séra, 2
mM L-glutaminu a 25 pg/ml gentamycinu (který může být získán od Gibco, Grand Island, New York). Buňky jsou pěstovány pň koncentraci 2x105 buněk na jamku v 0,2 ml kompletního média v 96jamkových mikrotitračních destičkách se dnem ve tvaru „U“. Potenciální antigen, který má být testován (buď inaktivovaný BPN' jako pozitivní kontrola nebo varianta, která je předmětem tohoto vynálezu) je přidán v konečné koncentraci 40 pg/ml. Kultury jsou inkubovány při 37 °C v atmosféře 5% CO2. Popětidenní inkubaci je přidána 1 pCi/jamku methyl-3H-thymidinu a po 18 hodinách jsou buňky odebrány. Za míru množení T-buněk je považováno množství 3H-thymidinu zabudovaného buňkou, které je zjišťováno pomocí měření v kapalném scintiiátoru. Prostředky, které jsou předmětem tohoto vynálezu.
Zde uvedené varianty mohou být použity v jakékoli aplikaci, která je vhodná pro standardní proteázu. Jedním takovým příkladem jsou čistící prostředky. Protože varianty, které jsou předmětem tohoto vynálezu, mají žádoucím způsobem snížené alergenní a/nebo imunogenní vlastnosti, tyto varianty mohou být dále používány v aplikacích, které dosud minimálně využívaly proteázy. Příklady takových aplikací zahrnuji ty, v nichž varianty nezbytně přicházejí do těsného styku s lidskou kůží, jako při použiti prostředků osobní hygieny.
Čistící prostředky.
Varianty mohou být použity v čistících prostředcích, mimo jiné v pracích prostředcích, prostředcích pro čistění pevných povrchů, prostředcích na mytí nádobí a detergentových prostředcích pro automatické myčky.
Zde uvedené čistící prostředky obsahují účinné množství jedné nebo více variant, které jsou předmětem tohoto vynálezu, a nosič čistícího prostředku.
Zde používaný termín „účinné množství varianty“ nebo podobně, označuje množství varianty nezbytné pro dosažení proteolytické aktivity, potřebné v určitých druzích čistících prostředků. Taková účinná množství jsou snadno zjistitelná pro osoby s běžnou zkušeností v oboru a je to založeno na mnoha faktorech, jako je určitá použitá varianta, čistící aplikace, specifické složení čisticího prostředku a zda je požadován vlhký nebo suchý (např. ve formě granulí, tyčinky) prostředek a podobně. S výhodou obsahují čistící prostředky od 0,0001 % do 10 %, výhodněji od 0,001 % do 1 % a nejvýhodněji od 0,01 % do 0,1 % jedné nebo více variant, které jsou předmětem tohoto vynálezu. Několik příkladů různých čistících prostředků, kde mohou být varianty použity, je dále diskutováno detailně.
*· 9···
9 • 9 99 .:.....· ·..· ·..· ·
Navíc k variantám, které jsou předmětem tohoto vynálezu, předkládané Čistící prostředky obsahují dále nosiče čistících prostředků, obsahující jeden nebo více materiálů čistícího prostředku, které jsou s variantou slučitelné. Zde používaný termín „materiál čistícího prostředku** znamená jakýkoli materiál, vybraný pro určitý typ £ požadovaného čistícího prostředku a formy tohoto výrobku (např. tekutina, granule, ' tyčinka, sprej, tyčka, pasta, gel), přičemž tyto materiály jsou také slučitelné s variantou,
L použitou v prostředku. Specifický výběr materiálů pro čistící prostředky je snadno proveditelný, když se vezme v úvahu materiál, který bude čištěn a požadovaná forma í prostředku pro podmínky, za kterých bude čistění probíhat. Zde používaný termín
Γ ' „slučitelný“ znamená materiály v čistícím prostředku, které nesnižují proteolytickou ! ( aktivitu varianty, v takovém rozsahu, že by varianta neměla při použití za normální f situace požadovanou účinnost. Specifické materiály čistících prostředků jsou zde dále detailně uvedeny.
Varianty, které jsou předmětem tohoto vynálezu, mohou být použity v různých detergentových prostředcích, kde je vyžadována vysoká pěnící a dobrá čistící aktivita. Varianty tedy mohou být použity spolu s různými běžnými složkami, aby bylo dosaženo přesně definovaných prostředků na čištění pevných povrchů, prostředků na mytí nádobí, prostředků na praní tkanin a podobně. Takové prostředky mohou být ve formě tekutin, granulí, tyčinek a podobně. Tyto prostředky mohou také být připraveny jako „koncentrované“ detergenty, které obsahují mezi 30 až 60 hmotnostními procenty smáčedel.
* Jako příklady zde užitečných smáčedel lze mimo jiné uvést běžné Cn-C18 alkyl benzensulfonáty a primární a náhodné alkylsulfáty, Cio-C18 sekundární (2,3) alkyl sulfáty obecných vzorců CH3(CH2)x(CHOSO3)'M+)CH3 a CH3(CH2)y(CHOSO3’M+) CH2CH3, kde x a (y+1) jsou celá čísla o velikosti alespoň 7, výhodně alespoň 9 a M je ve vodě rozpustný kation, zvláště sodík, CitrCi8 alkylalkoxysulfáty (zvláště EO 1-5
Ϊ ethoxysulfáty), CnrC18 alkylalkoxykarboxyláty (zvláště EO 1-5 ethoxykarboxyláty), C1(r C,e alkylpolygiykozidy a jejich odpovídající sulfátované polyglykozidy, Ci2-Ci8 asulfonátované estery mastných kyselin, C12-Cie alkyl a alkyifenotalkoxyiáty (zvláště ethoxyláty a smíšené ethoxy/propoxyláty), C12-C18 betainy a sulfobetainy („sultainy“), Ci0-C18 aminoxidy a podobně. Zde je dávána přednost alkyialkoxysulfátům (AES) a alkylalkoxykarboxylátům (AEG). Použití takových smáčedel v kombinaci saminoxidem a/nebo betainovými nebo suitainovými smáčedly je také výhodné, záleží však na \
·· ·«·· • · * *e ·· * · • · · • · · • · · ·»* 99 požadavku toho, kdo prostředek sestavuje. Jiná běžně používaná smáčedla jsou uvedena v běžných textech z tohoto oboru. Obzvláště vhodná smáčedla zahrnují C12C18 N-methylgíukamidy, popsané v patentu US č. 5 194 639, Connor a kol., vydaný 16. března 1993.
V zde obsažených detergentových čistících prostředcích se může vyskytovat množství rozmanitých jiných příměsí, například jiné aktivní příměsi, nosiče, činidla udržující vlhkost, barvy nebo pigmenty a u tekutých přípravků rozpouštědla. Jestliže je požadován další zvýšení pěnivosti, mohou být do prostředku přidány zesilovače pěnivosti, jako jsou C«rCi6 alkolamidy, typicky v množství 1 až 10 %. C10-C14 monoethanol a diethanolamidy jsou příkladem typické skupiny takových zesilovačů pěnivosti. Výhodné je také použití těchto zesilovačů pěnivosti spolu s vysoce pěnícími pomocnými smáčedly, jako jsou výše uvedené aminoxidy, betainy a sultainy. Pokud je to žádoucí, mohou být přidány rozpustné hořečnaté soli, jako jsou MgCI2, MgSO4 a podobně, v typických množstvích od 0,1 do 2 %, aby se dále podpořila pěnivost.
Tekuté detergentové prostředky, zde uvedené, mohou obsahovat jako nosiče vodu a jiná rozpouštědla. Vhodné jsou nízkomolekulární primární a sekundární alkoholy, jako jsou methanol, ethanol, propanol a izopropanol. Pro rozpouštění smáčedel jsou výhodné jednoduché alkoholy, ale mohou být také použity polyalkoholy, které obsahují 2 až 6 uhlíkových atomů a 2 až 6 hydroxylových skupin (např. 1,3propandiol, ethyíenglykol, glycerin a 1,2-propandiol). Prostředky mohou obsahovat 5 až 90 %, typicky však od 10 do 50 % takových nosičů.
S výhodou budou zde uvedené detergentové prostředky sestaveny tak, že během používáni pro čištění ve vodném prostředí, bude mít mycí voda pH mezi 6,8 a
11. Leštící prostředky jsou typicky takto sestaveny. Techniky pro kontrolu pH při doporučených způsobech použití, zahrnují použití například pufrů, zásad a kyselin. Tyto techniky jsou dobře známé osobám se zkušenostmi v tomto oboru.
Při sestavování prostředků pro čištění pevných povrchů a prostředků pro čištění tkanin, které jsou předmětem tohoto vynálezu, si pracovník může přát použít různé komponenty ve váhovém množstvích od 5 do 50 %. Typické komponenty zahrnují 1 až 10 mikronové zeolity, polykarboxyláty jako je citronan a oxydisukcináty, vrstevnaté silikáty, fosfáty a podobně. Ostatní běžné komponenty jsou uvedeny v běžných receptech.
·· « « · • 9 9 · ·· ···· · ·· ·· ·· ········«··
I ··········♦ ι «··········
I 70 · · ··· ···· / O ······· ····· ····
I Pracovník si může rovněž přát použít v těchto prostředcích různé další enzymy, jako
I jsou celulázy, lipázy a proteázy, typicky v množstvích od 0,001 do 1 %. Rozličné čistící enzymy a enzymy vhodné pro péči o tkaniny jsou dobře známé v oboru pracích detergentů.
V těchto prostředcích mohou být použity rozličné bělící sloučeniny, jako jsou peroxouhličitany, peroxoboritany a podobně, typicky v množstvích 1 až 15 | hmotnostních procent Pokud je to žádoucí, tyto prostředky mohou také obsahovat t aktivátory bělidel, jako jsou tetraacetylethylendiamin, nonanoyloxybenzen sulfonát a t ’ podobně, které jsou také v oboru známé. Používají se typicky v množstvích od 1 do 10
J * hmotnostních procent.
; V těchto prostředcích mohou být také použita činidla pro uvolnění špíny, zvláště typu aniontových oligoesterů, chelatační činidla, zvláště aminofosfonáty a ethylen diaminodisukcináty, činidla pro uvolnění zeminy, zvláště ethoxylovaný tetraethylenpentamin, dispergující činidla, zvláště polyakryláty a polyaspartáty, leštidla, zvláště aniontová leštidla, činidla potlačující pěnivost, zvláště silikony a sekundární alkoholy, změkčovače tkanin, zvláště valchářské hlíny a podobné, všechny mohou být použity v těchto prostředcích v množstvích od 1 do 35 hmotnostních procent. Standardní popisy složení a publikované patenty obsahují mnohé podrobné popisy těchto běžných materiálů.
V čistících prostředcích mohou být také použity stabilizátory enzymů. Tyto enzymové stabilizátory zahrnují propylenglykol (výhodně v koncentraci od 1 do 10 %), * mravenčan sodný (výhodně v koncentraci od 0,1 do 1,0 %) a mravenéan vápenatý (výhodně v koncentraci od 0,1 do 1,0 %).
* Varianty, které jsou předmětem tohoto vynálezu, jsou vhodné pro použití v ' čistících prostředcích na pevné povrchy. Zde používaný termín „čistící prostředky na pevné povrchy“ označuje tekuté a granulám! detergentové prostředky pro čistění pevných povrchů, jako jsou podlahy, stěny, koupelnové kachlíky a podobně. Prostředky pro čistění pevných povrchů, které jsou předmětem tohoto vynálezu, obsahují účinné množství jedné nebo více variant, které jsou předmětem tohoto vynálezu, s výhodou v koncentraci od 0,001 do 10 hmotnostních procent, výhodněji v koncentraci od 0,01 do 5 hmotnostních procent, ještě výhodněji v koncentraci od 0,05 do 1 hmotnostního procenta varianty v prostředku. Vedle toho, že obsahují jednu nebo více variant, typicky tyto čistící prostředky na pevné povrchy obsahují smáčedla a ve vodě rozpustné i
* « ··· odlučovací komponenty. V určitých specializovaných produktech, jako jsou sprejové čističe oken, však někdy nejsou smáčedla používána, protože mohou vytvářet filmy a/nebo zbytkové skvrny na skleněném povrchu.
Složka smáčidla, pokud je přítomna, může představovat pouze 0,1 % zde . uvedených prostředků, ale typicky budou prostředky obsahovat od 0,25 do 10 %, jL výhodněji od 1 do 5 % smáčidla.
I Prostředky budou typicky obsahovat od 0,5 do 50 % detergentových komponent, ř s výhodou od 1 do 10% detergentových komponent.
/ * S výhodou by mělo být pH v oblasti od 7 do 12. Pokud je to nezbytné, je možno f? pro úpravu pH použít běžná činidla pro úpravu pH, jako jsou hydroxid sodný, uhličitan sodný nebo kyselina chlorovodíková.
V prostředcích mohou být obsažena rozpouštědla. Vhodná rozpouštědla zahrnují mimo jiné glykolově étery, jako jsou diethylenglykol monohexyl éter, diethylenglykól monobutyl éter, ethylenglykol monobutyl éter, ethylenglykol monohexyl éter, propylenglykol monobutyl éter, dipropylenglykoi monobutyl éter a dioly, jako jsou
.. I
2,2,4-trimethyl-1,3-pentandiol a 2-ethyl-1,3-hexandiol. Pokud jsou použity, jsou tato rozpouštědla přítomná v množstvích od 0,5 do 15 %, s výhodou 3 do 11 %.
Dále mohou být použity v prostředcích, které jsou předmětem tohoto vynálezu, vysoce těkavá rozpouštědla, jako jsou izopropanol nebo ethanol, aby se urychlilo odpařováni prostředku z povrchů, když povrchy nejsou po použití prostředku opláchnuty. Pokud jsou použity, jsou tato těkavá rozpouštědla přítomná v množstvích od 2 do 12%.
Příklady provedení vynálezu
Prostředky pro čištění pevných povrchů, které jsou předmětem tohoto vynálezu, jsou ukázány na následujících příkladech.
Příklady 1 až 6
Tekuté prostředky pro čištění pevných povrchů
| Př. 1 | Př. 2 | Př. 3 | Př. 4 | Př. 5 | Př. 6 | |
| G70* + S78* + 1179* | 0,05 % | 0,50 % | 0,02 % | 0,03 % | 0,30 % | 0,05 % |
| EDTA | - | - | 2,90 % | 2,90 % | - | - |
| citronan sodný | - | - | - | - | 2,90 % | 2,90 % |
| NaCi2 alkylbenzensulfonát | 1,95% | - | 1,95% | - | 1,95% | - |
| NaCi2 alkylsulfát | - | 2,20 % | - | 2,20 % | - | 2,20 % |
| NaCi2 (ethoxy)sulfát | - | 2,20 % | - | 2,20 % | - | 2,20 % |
| C12 dimethylaminoxid | - | 0,50 % | - | 0,50 % | - | 0,50 % |
| Na kumensulfonát | 1,30% | - | 1,30% | - | 1,30% | - |
| hexylkarbitol | 6,30 % | 6,30% | 6,30 % | 6,30 % | 6,30 % | 6,30 % |
| voda | 90,4 % | 88,3 % | 87,53 % | 85,87 % | 87,25 % | 85,85 % |
Všechny předpisy jsou upraveny na pH 7.
V příkladech 1 až 6 jsou varianty uvedené v tabulkách 2 až 10 a výhodné varianty tam uvedené, zaměněny za G70* + S78* + 1179*, v podstatě s podobnými výsledky.
V jiném provedení předloženého vynálezu, obsahují prostředky na mytí nádobí jednu nebo více variant, které jsou předmětem tohoto vynálezu. Zde používaný výraz „prostředky na mytí nádobí“ označuje všechny formy prostředků pro čištění nádobí, mimo jiné v granulované a tekuté formě. Prostředky na mytí nádobí, které jsou předmětem tohoto vynálezu, jsou ukázány na následujících příkladech.
Příklady 7 až 10
Tekuté detergenty na mytí nádobí • · * · · · ··''·· ···· ·· « · ·· « • ·· · · · · · ·· · • ··· ···· ·· ··· ··· ·· ·· ··
| Př. 7 | Př. 8 | Př. 9 | Př. 10 | |
| G70* + L75* + N76* + N77* + S78* + I79* + G80* + V81* + L82* | 0,05 % | 0,50 % | 0,02 % | 0,40% |
| C12 - Cm N-methylglukamid | 0,90 % | 0,90 % | 0,90% | 0,90% |
| C12 ethoxy (1) sulfát | 12,0% | 12,0% | 12,0 % | 12,0% |
| 2-methylundekanová kyselina | 4,50 % | 4,50 % | 4,50% | 4,50% |
| Ci2 ethoxy (2) karboxylát | 4,50% | 4,50% | 4,50% | 4,50% |
| Ci2 alkohol ethoxylát (4) | 3,00% | 3,00% | 3,00% | 3,00% |
| C12 aminoxid | 3,00% | 3,00 % | 3,00% | 3,00% |
| Na kumensulfonát | 2,00% | 2,00% | 2,00% | 2,00 % |
| ethanol | 4,00 % | 4,00% | 4,00 % | 4,00% |
| Mgz+ (jako MgCI2) | 0,20 % | 0,20 % | 0,20 % | 0,20% |
| Ca2+ (jako CaCI2) | 0,40% | 0,40% | 0,40% | 0,40% |
| voda | 65,45% | 65 % | 65,48% | 65,1 % |
Všechny předpisy jsou upraveny na pH 7.
Vpřikiadech 7 až 10 jsou varianty uvedené v tabulkách 2 až 10 a výhodné i
varianty tam uvedené, zaměněny za G70* + L75* + N76* + N77* + S78* + ,79* + G80* + V81* + L82*, v podstatě s podobnými výsledky.
Tekuté prostředky pro čištění tkanin, které jsou předmětem tohoto vynálezu, jsou ukázány na následujicích příkladech.
Příklady 11 až 13
Tekuté prostředky pro čištěni tkanin
| Př. 8 | Př. 9 | Př. 10 | |
| G70* | 0,05 % | 0,03 % | 0,30 % |
| C12 - Cu alkylsulfát sodný | 20,0 % | 20,0 % | 20,0 % |
| 2-butyl oktanová kyselina | 5,0 % | 5,0 % | 5,0 % |
| citronan sodný | 1,0% | 1,0% | 1,0% |
| Ci2 alkohol ethoxylát (3) | 13,0% | 13,0% | 13,0% |
| monoethanoiamin | 2,50 % | 2,50 % | 2,50 % |
| voda/propylenglykol/ethanol (100:1:1) | 58,45% | 58,47 % | 58,20 % |
• · ··
τ i,
Ί.
V příkladech 11 až 13 jsou varianty uvedené v tabulkách 2 až 10 a výhodné varianty tam uvedené, zaměněny za G70*, v podstatě s podobnými výsledky.
Prostředky pro osobní hygienu.
Předložené varianty jsou obzvláště vhodné pro použití v prostředcích pro osobní hygienu, jako jsou například vlasové kondicionéry, šampóny, prostředky proti akné, pleťová mléka a kondicionéry, sprchové gely, mýdla, pěnivé a nepěnivé prostředky pro čištění pleti, kosmetika, pleťová mléka a zvlhčovače na ruce, obličej a tělo, kosmetické a čistící kapesníky, prostředky ústní hygieny a prostředky pro péči o kontaktní čočky. Prostředky pro osobní hygienu, které jsou předmětem tohoto vynálezu, obsahují jednu nebo více předkládaných variant a nosič pro prostředky pro osobní hygienu.
Pro ilustraci, varianty, které jsou předmětem tohoto vynálezu, jsou vhodné pro zahrnutí do prostředků, popsaných v následujících odkazech: patent US č. 5 641 479, Linares a kol., vydaný 24. června 1997 (prostředky pro čištění pleti); patent US č. 5 599 549, Wivell a kol., vydaný 4. února 1997 (prostředky pro čištění pleti); patent US č. 5 585 104, Ha a kol., vydaný 7. prosince 1996 (prostředky pro čištění pleti); patent US č. 5 540 852, Kefauver a kol., vydaný 30. července 1996 (prostředky pro čištění pleti); patent US č. 5 510 050, Dunbar a kol., vydaný 23 dubna 1996 (prostředky pro čištění pleti); patent US č. 5 612 324, Guang Lin a kol., vydaný 18. března 1997 (prostředky proti akné); patent US č. 5 587 176, Warren a kol., vydaný 24. prosince 1996 (prostředky proti akné); patent US č. 5 549 888, Venkateswarari, vydaný 27. srpna
1996 (prostředky proti akné); patent US č. 5 470 884, Corless a kol., vydaný 28. listopadu 1995 (prostředky proti akné); patent US č. 5 650 384, Gordon a kol., vydaný 22. července 1997 (sprchové gely); patent US č. 5 607 678, Moore a kol., vydaný 4. března 1997 (sprchové gely); patent US č. 5 624 666, Coffindaffer a kol., vydaný 29. dubna 1997 (vlasové kondicionéry a/nebo šampóny); patent US č. 5 618 524, Bolich a kol., vydaný 8. dubna 1997 (vlasové kondicionéry a/nebo šampóny); patent US č. 5 612 301, vydaný Inman, 18. března 1997 (vlasové kondicionéry a/nebo šampóny); patent US č. 5 573 709, Wells, vydaný 12. listopadu 1996 (vlasové kondicionéry a/nebo šampóny); patent US č. 5 482 703, Pings, vydaný 9. ledna 1996 (vlasové kondicionéry a/nebo šampóny); patent US č. Re. 34 584, Grota a kol., znovu vydaný 12. dubna 1994 (vlasové kondicionéry a/nebo šampóny); patent US č. 5 641 493, Dáte a kol., vydaný 24.června 1997 (kosmetika); patent US č. 5 605 894, Blank a kol., vydaný 25. února
1997 (kosmetika); patent US č. 5 585 090, Yoshioka a kol., vydaný 17. prosince 1996 • ·
(kosmetika): patent US č. 4 939 179, Cheney a kol., vydaný 3. července 1990 (pleťová mléka na ruce, obličej a/nebo tělo); patent US č. 5 607 980, McAtee a kol., vydaný 4. března 1997 (pleťová mléka na ruce, obličej a/nebo tělo); patent US č. 4 045 364, Richter a kol., vydaný 30. srpna 1977 (kosmetické a čistící kapesníky); žádost o evropský patent EP 0 619 074, Touchet a kol., publikovaný 12. října 1994 (kosmetické a čistící kapesníky); patent US č. 4 975 217, Brown-Skrobot a kol., vydaný 4. prosince 1990 (kosmetické a čistící kapesníky); patent US č. 5 096 700, Seibel, vydaný 17. března 1992 (prostředky ústní hygieny); patent US č. 5 028 414, Sampathkumar, vydaný 2. července 1991 (prostředky ústní hygieny); patent US č. 5 028 415, Benedict a kol., vydaný 2. července 1991 (prostředky ústní hygieny); patent US č. 5 028 415, Benedict a kok, vydaný 2. července 1991 (prostředky ústní hygieny); patent US č. 4 863 627, Davies a kol., 5. září 1989 (prostředky pro péči o kontaktní čočky); patent US č. Re. 32 672, Huth a kol., znovu vydaný 24. května 1988 (prostředky pro péči o kontaktní čočky) a patent US č. 4 609 794, Schafer, vydaný 2. září 1986 (prostředky pro péči o kontaktní čočky).
Pro další ilustraci prostředků ústní hygieny, které jsou předmětem tohoto vynálezu, je farmaceuticky přijatelné množství jedné nebo více variant, které jsou předmětem tohoto vynálezu, obsaženo v prostředcích vhodných pro odstraňování proteinových skvrn ze zubů nebo umělého chrupu. Zde používaný termín „prostředky ústní hygieny“ označuje prostředky na čištění zubů, zubní pasty, zubní gely, zubní prášky, ústní vody, ústní spreje, ústní gely, žvýkačky, zdravotní pastilky, ústní parfémy, tablety, biogely, pasty pro prevenci, zubní léčebné roztoky a podobně. S výhodou obsahují prostředky ústní hygieny od 0,0001 do 20 hmotnostních procent jedné nebo více variant, které jsou předmětem tohoto vynálezu, výhodněji od 0,01 do 10 hmotnostních procent, ještě výhodněji od 0,01 do 5 hmotnostních procent prostředku a farmaceuticky přijatelný nosič. Zde používaný termín „farmaceuticky přijatelný“ znamená, že látky, léky nebo inertní složky, které termín popisuje, jsou vhodné použít ke styku s tkáněmi lidí a nižších živočichů bez nepřiměřené toxicity, neslučivosti, nestability, podráždění, alergické odpovědi a podobně, přiměřeně s rozumným poměrem zlsk/riziko.
V typickém případě budou farmaceuticky přijatelné složky nosiče pro složky pro ústní čištění v prostředcích ústní hygieny tvořit od 50 do 99,99 hmotnostních procent, • ·
výhodněji od 65 do 99,99 hmotnostních procent a ještě výhodněji od 65 do 99 hmotnostních procent prostředku.
Farmaceuticky přijatelné složky nosiče a volitelné složky, které mohou být zahrnuty v prostředcích ústní hygieny, které jsou předmětem tohoto vynálezu, jsou dobře známé osobám se zkušeností v tomto oboru. Velká rozmanitost typů prostředků, nosičových složek a volitelných složek, vhodných pro prostředky ústní hygieny, jsou popsány v odkazech, které zde byly výše citovány.
V jiném provedení předloženého vynálezu, prostředky pro čištění zubních protéz, používané pro čištění zubních protéz mimo dutinu ústní, obsahují jednu nebo více variant, které jsou předmětem tohoto vynálezu. Tyto prostředky pro čištění zubních protéz obsahují účinné množství jedné nebo více variant, s výhodou v množství od 0,0001 do 50 hmotnostních procent jedné nebo více variant, výhodněji od 0,001 do 35 hmotnostních procent, ještě výhodněji od 0,01 do 20 hmotnostních procent prostředku a nosič, vhodný pro čištění zubních protéz. Různé formáty prostředků pro čištění zubních protéz, jako jsou šumící tablety a podobně jsou v oboru dobře známé (viz např. patent US č. 5 055 305, Young) a obecně jsou vhodné pro zabudování jedné nebo více variant pro odstranění proteinových skvrn z umělého chrupu.
V jiném provedení předloženého vynálezu, prostředky pro čištění kontaktních čoček obsahují jednu nebo více variant, které jsou předmětem tohoto vynálezu. Tyto prostředky pro čištění kontaktních čoček obsahují účinné množství jedné nebo více variant, s výhodou v množství od 0,01 do 50 hmotnostních procent jedné nebo více variant, výhodněji od 0,01 do 20 hmotnostních procent, ještě výhodněji od 1 do 5 hmotnostních procent prostředku a nosič, vhodný pro čištění kontaktních čoček. Různé formáty prostředků pro čištění kontaktních čoček, jako jsou tablety, kapaliny a podobně jsou rovněž v oboru dobře známé a obecně jsou vhodné pro zabudováni jedné nebo více variant, které jsou předmětem tohoto vynálezu, pro odstranění proteinových skvrn z kontaktních čoček.
Provedení prostředků pro čištění kontaktních čoček, které jsou předmětem tohoto vynálezu, jsou ukázány na následujících příkladech 14 až 17.
• ·
Příklady 14 až 17
Roztoky pro čištění kontaktních čoček
| Př. 14 | Př. 15 | Př. 16 | Př. 17 | |
| N76* | 0,01 % | 0,5 % | 0,1 % | 2,0 % |
| glukóza | 50,0% | 50,0 % | 50,0 % | 50,0% |
| neiontové smáčedlo (kopolymer polyoxyethylenu a polyoxypropylehu) | 2,0 % . | 2,0% | 2,0% | 2,0% |
| aniontové smáčedlo (polyoxyethylen - Na alkylfenyléter sulfricester) | 1,0% | 1,0% | 1,0% | .1,0% |
| chlorid sodný | 1,0% | 1,0% | 1,0% | 1,0% |
| borax | 0,30% | 0,30 % | 0,30 % | 0,30% |
| voda | 45,69% | 45,20 % | 45,60 % | 43,70 % |
V příkladech 14 až 17 jsou varianty uvedené v tabulkách 2 až 10 a výhodné varianty tam uvedené, zaměněny za N72*, v podstatě s podobnými výsledky.
Příklady 18 až 21 představují použití předložených variant ve výrobcích, používaných pro mytí těla:
Příklady 18 až 21 Výrobky pro mytí těla
| Př. 18 | Př. 19 | Př. 20 | Př. 21 | |
| voda | 62,62 % | 65,75 % | 57,72 % | 60,72 % |
| Na2 EDTA | 0,2% | 0,2 % | 0,2 % | 0,2 % |
| glycerin | 3,0 % | 3,0 % | 3,0 % | 3,0 % |
| Polyquaternium 10 | 0,4 % | 0,4% | 0,4 % | 0,4 % |
| Na laureth sulfát | 12,0% | 12,0 % | 12,0 % | 12,0 % |
| cocamide MEA | 2,8 % | 2,8 % | 2,8 % | 2,8 % |
| Na „lauraphoacetate“ | 6,0 % | 6,0 % | 6,0 % | 6,0 % |
| kyselina myristilová | 1,6% | 1,6% | 1,6% | 1,6% |
| MgSO4.7H2O | 0,3 % | 0,3% | 0,3 % | 0,3 % |
| trihydroxystearin | 0,5% | 0,5 % | 0,5 % | 0,5 % |
| PEG-6 triglyceridy kyselin kaprylové/kaprové | 3,0 % |
| sacharózové polyestery „cottonate“ mastné kyseliny | 3,0% | |||
| sacharózové polyestery „behenate“ mastné kyseliny | 3,0 % | 4,0% | ||
| vazelína z ropy | - | 4,0 % | 8,0 % | - |
| minerální olej | - - | - | - | 6,0% |
| DMDM hydantoin | 0,08 % | 0,08% | 0,08% | 0,08 % |
| G70* + L75* + N76* + N77* + S78* + I79* + G80* + V81* + L82* | 0,1 % | 2,0 % | 2,0% | 5,0% |
| kyselina citrónová | 1,40% | 1,40% | 1,40 % | 1,40% |
V příkladech 18 až 21 jsou varianty uvedené v tabulkách 2 až 10 a výhodné varianty tam uvedené, zaměněny za G70* + L75* + N76* + N77* + S78* + I79* + G80* + V81* + L82*, v podstatě s podobnými výsledky.
Příklady 22 až 25 představují použití předložených variant ve výrobcích, používaných pro ošetřování pleti na obličeji.
Příklady 22 až 25
Výrobky pro ošetřování pleti na obličeji
| Př. 22 | Př. 23 | Př. 24 | Př. 25 | |
| voda | 66,52 % | 65,15% | 68,47 % | 68,72 % |
| Na2 EDTA | 0,1 % | 0,1 % | 0,2 % | 0,2 % |
| kyselina citrónová | - | - | 1,4% | 1,4% |
| Na laureth-3 sulfát | 3,0 % | 3,5 % | - | - |
| Na laureth-4 karboxylát | 3,0 % | 3,5 % | - | - |
| Polyquatemium 10 | - | - | 0,4 % | 0,4 % |
| Polyquaternium 25 | 0,3 % | 0,3 % | - | - |
| glycerin | 3,0 % | 3,0 % | 3,0 % | 3,0 % |
| Na Jauraphoacetate“ | - | - | 6,0 % | 6,0 % |
| kyselina laurová | 6,0 % | 6,0 % | 3,0% | 3,0 % |
| kyselina myristilová | - | - | 3,0 % | 3,0 % |
| MgSO4.7H2O | 2,3 % | 2,0 % | 2,0% | 2,0 % |
| triethanoiamin | 4,0 % | 4,0 % | 4,0 % | 4,0 % |
• · «tři
| trihydroxystearin ~ | 0,5 % | 0,5% | 0,5% | 0,5% |
| sacharózové polyestery „behěnate“ mastné kyseliny | 2,0 % | 2,0 % | ||
| sacharózové polyestery „cottonate“ mastné kyseliny | 3,0 % | 2,0 % | ||
| PEG-6 triglyceridy kyselin kaprylové/kaprové | 2,0% | |||
| vazelína z ropy | - | 4,0 % | - | |
| minerální olej | - | - | - | 2,0 % |
| kokamidopropyl betain | 2,0 % | 3,0 % | 1,8% | 1,8% |
| lauryldimethylaminoxid | 1,0% | 1,2% | 1,2% | 1,2% |
| dexpanthenol | 1,0% | 0,25% | 0,25 % | - |
| DMDM hydantoin | 0,08 % | 0,08% | 0,08 % | 0,08 % |
| Δ 73,179M | 1,0% | 2,0% | 2,0 % | 0,5 % |
| vůně | 0,2% | 0,2 % | 0,2% | 0,2 % |
V příkladech 22 až 25 jsou varianty uvedené v tabulkách 2 až 10 a výhodné varianty tam uvedené, zaměněny za Δ 73,179M, v podstatě s podobnými výsledky.
Příklady 26 až 27 představují použití předložených variant v prostředcích, používaných pro zvlhčování pleti:
Příklady 26 až 27 Výrobky pro zvlhčování pleti
| příklad 26 | příklad 27 | |
| glycerin | 5,0 % | - |
| kyselina stearová | 3,0 % | - |
| C11-13 izoparafin | 2,0 % | - |
| glykolstearát | 1,5% | - |
| propylenglykol | - | 3,0 % |
| minerální olej | 1,0% | 10,0% |
| sezamový olej | - | 7,0 % |
| vazelína z ropy | - | 1,8% |
| triethanolamin | 0,7% | - |
··«··· · · · · · · · « ·· «· * · · V-·>. i· • · ·· · · · 4 4 « f • · * ·· · · · · « ·
| cetyloctan | 0,65 % | - |
| glycerinstearát | 0,48 % | 2,0 % |
| TEA stearát | - | 2,5 % |
| cetylalkohol | 0,47 % | - |
| lanolinalkohol | - | 1,8% |
| DEA cetylfosforečnan | 0,25% | - |
| methylparaben | 0,2 % | 0,2% |
| propylparaben | 0,12% | 0,1 % |
| carbomer 934 | 0,11 % | - |
| Na2EDTA | 0,1 % | - |
| L82* | 0,1 % | 0,5 % |
| voda | 84,32% | 71,1 % |
V příkladech 26 až 27 jsou varianty uvedené v tabulkách 2 až 10 a výhodné varianty tam uvedené, zaměněny za L82*, v podstatě s podobnými výsledky.
Příklad 28 představuje použití předložených variant v prostředcích, používaných v čistících kapesnících:
Příklad 28
Prostředek, používaný v čistících kapesnících
| propylenglykol | 1,0% |
| laurylsíran amonný | 0,6 % |
| kyselina jantarová | 0,4 % |
| jantaran sodný | 3,2 % |
| Tricíosan® | 0,15 % |
| S78* | 0,05 % |
| voda | 91,0% |
Výše uvedeným prostředkem je napuštěn arch tkaniny, složený z celulózy a/nebo polyesteru v množství 250 % váhy absorbujícího archu.
V příkladu 28 jsou varianty uvedené v tabulkách 2 až 10 a výhodné varianty tam uvedené, zaměněny za S78*, v podstatě s podobnými výsledky.
Claims (10)
- Varianta serinové proteázy, vyznačující se t í m, že má pozměněnou aminokyselinovou sekvenci standardní aminokyselinové sekvence, obsahující substituci na jedné pozici, odpovídající pozicím 70 až 84, subtilizinu BPN', přičemž:(a) pokud substituce nastane na pozici 70, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cýs, Glu, Phe, His, lle, tys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;(b) pokud substituce nastane na pozici 71, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Cys, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Ser, Trp, Tyr a Val;(c) pokud substituce nastane na pozici 72, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp a Tyr;(d) pokud substituce nastane na pozici 73, substituující aminokyselina pochází ze skupiny, obsahující Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, lle, Lys, Met, Pro, Ser, Thr, Trp, Tyr a Val; ’ (e) pokud substituce nastane na pozici 74, substituující aminokyselina pochází ze skupiny, obsahující Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;(f) pokud substituce nastane na pozici 75, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, lle, Lys, Met, Gin, Ser, Thr, Trp, Tyr a Val;(g) pokud substituce nastane na pozici 76, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Cys, lle, Leu, Met, Pro, Gin, Ser, Thr, Tip, Tyr a Val;(h) pokud substituce nastane na pozici 77, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Cys, Glu, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;(i) pokud substituce nastane na pozici 78, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Cys, Glu, Gly, Phe, His, lle, Lys, Leu, Met, Pro, Gin, Thr, Trp, Tyr a Val;(j) pokud substituce nastane na pozici 79, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Cys, Gly, Phe, His, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;(k) pokud substituce nastane na pozici 80, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val;(l) pokud substituce nastane na pozici 81, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp a Tyr;(m) pokud substituce nastane na pozici 82, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Gly, Phe, His, Ile, Lys, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Vál;(n) pokud substituce nastane na pozici 83, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Glu, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp, Tyr a Val; a (o) pokud substituce nastane na pozici 84, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Čys, Glu, Gly, Phe, His, Ile, Lys; Leu, Met, Pro, Gin, Ser, Thr, Trp a Tyr.
- 2. Varianta serinové proteázy, v y z n a č u j í c í s e tím, že má pozměněnou aminokyselinovou sekvenci standardní aminokyselinové sekvence, obsahující substituce na dvou nebo více pozicích, odpovídajících pozicím 70 až 84, subtilizinu BPN', přičemž:(a) pokud substituce nastane na pozici 70, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;(b) pokud substituce nastane na pozici 71, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Trp, Tyr a Val;(c) pokud substituce nastane na pozici 72, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Gin, Ser, Thr, Trp a Tyr;i t(d) (e) (f) (9) (h) (i) (i) (k) (l) (m) (n) pokud substituce nastane na pozici 73, substituující aminokyselina pochází ze skupiny, obsahující Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu,Met, Pro, Ser, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 74, substituující aminokyselina pochází ze skupiny, obsahující Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 75, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Met, Pro, Ser, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 76, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asp, Cys, Gin, Glu, Giy, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 77, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 78, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 79, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 80, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 81, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp a Tyr;pokud substituce nastane na pozici 82, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Met, Pro, Ser, Thr, Trp, Tyr a Val;pokud substituce nastane na pozici 83, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp, Tyr a Val; a ·· 99999 99 999 (o) pokud substituce nastane na pozici 84, substituující aminokyselina pochází ze skupiny, obsahující Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, Phe, His, Ile, Lys, Leu, Met, Pro, Ser, Thr, Trp a Tyr;kde není varianta Asn76Asp + Asn77Asp; Asn76Asp + He79Gíu nebo Asn76Asp + Ser79Asp.
- 3. Varianta-podle-nároků-Va-2, v y.z n a č u i í c í se tím, že že serinové proteáza je vybrána ze skupiny, obsahující subtilizin BPN', subtilizin Carlsberg, subtilizin DY, subtilizín 309, proteinázu K a thermitázu.
- 4. Varianta podle kteréhokoli z předchozích nároků, vyznačující se t í m, že substituce je na jedné nebo více z pozic 73 - 83, odpovídajících subtilizinu BPN'.
- 5. Varianta podle kteréhokoli z předchozích nároků, vyznačující se t í m, že substituce je na jedné nebo více z pozic 70 a 75 - 82, odpovídajících subtilizinu BPN'.
- 6. Varianta podle kteréhokoli z předchozích nároků, v y z n a č u j í c í se tím, že dále obsahuje jednu nebo více stabilizujících mutací.
- 7. Varianta podle nároku 6, v y z n a č u j í c í se t í m, že stabilizující mutace vybrána ze skupiny, skládající se z I107V, K213R, Y217L, Y217K, N218S, G169A, M50F, Q19E, P5A, S9A, I31L, E156S, G169A, N212G, S188P, T254A, S3C + Q206C a Q271E.
- 8. Prostředek pro osobní hygienu, vyznačující se tím, že obsahuje variantu kteréhokoli z předchozích nároků a nosič prostředku pro osobní hygienu.
- 9. Čistící prostředek, vyznačující se tím, že obsahuje variantu kteréhokoli z předchozích nároků a nosič čistícího prostředku.
- 10. Mutovaný gen pro serinovou proteázu, vyznačující se tím, že kóduje variantu podle kteréhokoli z předchozích nároků.• e fl/í^ VSEZNAM SEKVENCÍ S (1) OBECNÉ INFORMACE (i) PŘIHLAŠOVATEL: RUBINGH, D.N. 'a kol.(ii) NÁZEV VYNÁLEZU: Varianta serinové proteázy, prostředek pro osobni hygienu, čistící prósťřěděk, mutovaný gen.(iii) POČET SEKVENCÍ: 1 ---------- _7 _ (iv) ADRESA PRO KORESPONDENCI:
(A) ADRESAT: THE PROCTER & GAMBLE COMPANY (B) ULICE: 11810 EAST MIAMI RIVER ROAD (C) MĚSTO: ROSS (D) STÁT: OH (E) ZEMĚ: USA (F) ZIP: 45061 (v) POČÍTAČOVÉ VYBAVENÍ:(A) TYP MÉDIA: Disketa (B) POČÍTAČ: IBM PC kompatibilní (C) OPERAČNÍ SYSTÉM: PC-DOS/MS-DOS (D) SOFTWARE: Patentln Release #1.0, Version #l.*30 (vi) ÚDAJE O PŘIHLÁŠCE:(A) ČÍSLO PŘIHLÁŠKY: r (B) DATUM PODÁNÍ:(C) KLASIFIKACE:(viii) ÚDAJE O PRÁVNÍM ZÁSTUPCI:(A) JMÉNO: HERSKO, Bart S.(B) REGISTRAČNÍ ČÍSLO: 32,572 (C) REFERENČNÍ ČÍSLO:(ix) INFORMACE O SPOJENÍ:(A) TELEFON: 513-627-0633 (B) TELEFAX: 513-627-0260 (2) INFORMACE K SEKVENCI Č.l:(i) CHARACTERISTIKY SEKVENCE:(A) DÉLKA: 275 aminokyselin (B) TYP: aminokyselina (D) TOPOLOGIE: lineární (ii) TYP MOLEKULY: protein (xi) POPIS SEKVENCE: Sekvence č.l:Ala 1 Gin Ser Val Pro 5 Tyr Gly Val Ser Gin 10 Ile Lys Ala Pro Ala 15 Leu His Ser Gin Gly 20 Tyr Thr Gly Ser Asn 25 Val Lys Val Ala Val 30 Ile Asp Ser Gly Ile 35 Asp Ser Ser His Pro 40 Asp Leu Lys Val Ala 45 Gly Gly Ala ··· «· ·· ·· «·· ···· ··«· ···· · · · · · · · • · · ·· ··· ·· · • · ······· ···· ··· ··· ·· ·· ·*Ser Met Val Pro Val Ser Ala Glu Thr Asn 55 Pro Ala Phe Gin Asp Asn Asn Ser Ile His Gly 80 50 Gly Thr 65 His Ala 60 Ser Gly 70 Thr Val Leu Asn 75 Asn Val Leu Gly Val Ala Pro Ser Ala Ser Leu Tyr Ala Val Lys Val Leu · .r- --- 85 ---- ... 90 ' ' — · - ------- 95 -------. Gly Ala Asp Gly Ser Gly Gin Tyr Ser Trp Ile Ile Asn Gly Ile Glu 100 105 110 Trp Ala Ile Ala Asn Asn Met Asp Val Ile Asn Met Ser Leu Gly Gly 115 120 125 Pro Ser Gly Ser Ala Ala Leu Lys Ala Ala Val Asp Lys Ala Val Ala 130 135 140 Ser Gly Val Val Val Val Ala Ala Ala Gly Asn Glu Gly Thr Ser Gly 145 150 155 160 Ser Ser Ser Thr Val Gly Tyr Pro Gly Lys Tyr Pro Ser Val Ile Ala 165 170 175 Val Gly Ala Val Asp Ser Ser Asn Gin Arg Ala Ser Phe Ser Ser Val 180 185 190 Gly Pro Glu Leu Asp Val Met Ala Pro Gly Val Sér Ile Gin Ser Thr 195 200 205 Leu Pro Gly Asn Lys Tyr Gly Ala Tyr Asn Gly Thr Ser Met Ala Ser 210 215 220 Pro His Val Ala Gly Ala Ala Ala Leu Ile Leu Ser Lys His Pro Asn 225 230 235 240 Trp Thr Asn Thr Gin Val Arg Ser Ser Leu Glu Asn Thr Thr Thr Lys 245 250 255 Leu Gly Asp Ser Phe Tyr Tyr Gly Lys Gly Leu Ile Asn Val Gin Ala 260 265 270 Ala Ala Gin 275
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| CZ20003397A CZ20003397A3 (cs) | 1999-03-25 | 1999-03-25 | Varianta serinové proteázy; prostředek pro osobní hygienu, čistící prostředek, mutovaný gen |
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