KR101818895B1 - 생물학적 활성이 감소된 신경독 - Google Patents
생물학적 활성이 감소된 신경독 Download PDFInfo
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Abstract
본 발명은 약학 분야에 관한 것이다. 구체적으로, 피험자에서 생물학적 효과 기간이 감소된 신경독 폴리펩티드를 인코딩하는 폴리뉴클레오티드에 관한 것으로서, 상기 폴리펩티드는 경쇄에서 적어도 하나의 분해 신호, 또한 상기 폴리뉴클레오티드, 이렇게 인코딩된 폴리펩티드, 폴리펩티드에 특이적으로 결합한 항체를 포함한 벡터 및 숙주 세포를 포함한다. 또한, 본 발명은 상기 폴리뉴클레오티드 및 폴리펩티드를 포함한 약제, 또한 그 특이적 치료 적용에 관한 것이다. 또한, 본 발명은 폴리펩티드 및 약제의 제조 방법에 관한 것이다.
Description
본 발명은 약학 분야에 관한 것이다. 구체적으로, 피험자 (subject)에서 생물학적 효과 기간이 감소된 신경독 폴리펩티드를 인코딩하는 폴리뉴클레오티드에 관한 것으로서, 상기 폴리펩티드는 경쇄에서 적어도 하나의 분해 신호 (degradation signal)를 포함할뿐만 아니라, 또한 상기 폴리뉴클레오티드, 이렇게 인코딩된 폴리펩티드, 폴리펩티드에 특이적으로 결합한 항체를 포함한 벡터 및 숙주 세포를 포함한다. 또한, 본 발명은 상기 폴리뉴클레오티드 및 폴리펩티드를 포함한 약제, 또한 그 특이적 치료 적용에 관한 것이다. 또한, 본 발명은 폴리펩티드 및 약제의 제조 방법에 관한 것이다.
보툴리누스균 및 파상풍균(Clostridium botulinum and Clostridium tetani) 은 각각 매우 강력한 신경독, 즉 보툴리눔 독소(BoNT) 및 파상풍 독소 (TeNT)를 생성한다. 이들 크로스티리디아성 신경독(CNT)은 뉴런 세포에 특이적으로 결합하고 신경전달물질 방출을 파괴한다. 각각의 독소는 비활성 미처리된 약 150 kDa 단쇄 단백질로서 합성된다. 번역후 처리는 디설피드 가교의 형성 및 세균성 프로테아제에 의한 한정된 단백질 분해효소(상성)를 수반한다. 활성 신경독은 2개의 사슬, 디술피드 결합에 의해서 결합된, 대략 50 kDa의 N-말단 경쇄 및 대략 100kDa의 중쇄로 이루어진다. CNT는 3개의 영역; 즉 촉매 경쇄, 전좌영역 (N-말단 절반) 및 수용체 결합 영역(C-말단 절반)을 포함한 중쇄로 이루어진다 (Krieglstein 1990, Eur J Biochem 188, 39; Krieglstein 1991, Eur J Biochem 202, 41; Krieglstein 1994, J Protein Chem 13, 49 참조.). 보툴리눔 신경독소는 150 kDa 신경독소 단백질 및 관련 비독성 복합 단백질을 포함한 분자의 복합물로서 합성된다. 상기 복합물의 크기는 크로스티리디아성 변종 및 300 kDa 내지 900 kDa의 범위의 독특한 신경독 항원형에 기초해서 다르다. 이들 복합물 내의 복합 단백질은 신경독을 안정화시키고, 그 분해로부터 보호한다(Chen 1998, Infect Immun 66(6): 2420-2425 참조).
보툴리누스균은 보툴리눔 신경독 (BoNT)의 7개의 항원적으로 독특한 항원형 A 내지 G를 분비한다. 파상풍균에 의해 분비된 관련된 파상풍 신경독(TeNT)과 함께 모든 항원형은 SNARE 단백질을 절단함으로써 시냅스 엑소사이토시스를 차단하는 Zn2 + 엔도프로테아제이다(Couesnon, 2006, Microbiology, 152, 759 참조). CNT는 보툴리눔 중독증에서 발견된 이완성 근육 마비를 일으킨다 (Fischer 2007, PNAS 104, 10447 참조).
독성 작용에도 불구하고, 보툴리눔 독소는 많은 질병 또는 장애의 치료제로서 사용되고 있다. 보툴리눔 독소 항원형 A는 사시성, 안검경련 및 다른 장애의 치료용으로 1989년 미국에서 인간에 대한 사용이 허가되었다. 예를 들면, 상품명 BOTOX (Allergan Inc), 상품명 DYSPORT (Ipsen Ltd)으로 보툴리눔 독소 A 단백질 복합물로서 시판된다. 치료 적용에 대해서, 복합물을 근육에 직접 주입해서 치료한다. 생리적인 pH에서, 단백질 복합물로부터 독소를 방출하고 소망의 약리작용이 발생한다. 개선된, 복합물이 함유되지 않은 신경독 A 폴리펩티드 제제는 상품명 XEOMIN (Merz Pharmaceuticals GmbH)으로 시판된다. 보툴리눔 독소의 작용은 일시적이고, 이것은 치료작용을 유지하기 위해서 보툴리눔 독소의 반복적인 투여를 필요로 하는 이유이다.
크로스티리디아성 신경독은 수의근 강도를 약하게 하고, 사시증, 국소성 근긴장이상증, 예를 들면 경부 근긴장이상증 및 양성 본태성 안검경련의 치료에 효과적이다. 이들은 안면경련 경감, 및 국소경직 경감시키고, 또한 광범위한 지표, 예를 들면 위장 장애, 다한증 및 미용성 주름 개선에서 효과적인 것을 나타낸다(Jost 2007, Drugs 67, 669 을 참조한다).
그러나, 근육 강도 및 수축 약화는 질환 또는 질병, 예를 들면 상처 치유, 뼈 및 힘줄 골절 치료를 위한 부동화, 구체적으로 치핵절제, 치과 임플란트 도입 또는 관절치환술(엔도프로테시스), 관절 형성, 안과 수술에 관련된 수술후 부동화, 여드름 또는 과민성 대장 증후군에 바람직하다. 신경독은 일반적으로 상기 질병 또는 질환의 효율적인 치료에 실제로 필요로 된 기간보다 긴 시간에 걸쳐서 생물학적 효과를 나타낸다. 장기간의 근육 마비는 상기 질환 또는 질병의 치료에서 유해하거나 적어도 덜 바람직하다. 이들의 생물학적 효과를 나타내는 신경독은 아직 이용가능하지 않다.
따라서, 본 발명의 근본적인 기술적인 문제는 상기 요구에 적합한 수단 및 방법을 제공하는 것이다. 기술적인 문제는 하기 기재된 및 청구범위에서 특징으로 하는 실시형태에 의해서 해결된다.
본 발명은 약학 분야에 관한 것이다. 구체적으로, 피험자에서 생물학적 효과 기간이 감소된 신경독 폴리펩티드를 인코딩하는 폴리뉴클레오티드에 관한 것으로서, 상기 폴리펩티드는 경쇄에서 적어도 하나의 분해 신호, 또한 상기 폴리뉴클레오티드, 이렇게 인코딩된 폴리펩티드, 폴리펩티드에 특이적으로 결합한 항체를 포함한 벡터 및 숙주 세포를 포함한다. 또한, 본 발명은 상기 폴리뉴클레오티드 및 폴리펩티드를 포함한 약제, 또한 그 특이적 치료 적용에 관한 것이다. 또한, 본 발명은 폴리펩티드 및 약제의 제조 방법에 관한 것이다.
본 발명은 피험자 내에 생물학적 효과 기간이 감소된 신경독 폴리펩티드를 인코팅하는 폴리뉴클레오티드에 관한 것으로, 상기 폴리펩티드는 경쇄에서 적어도 하나의 분해 신호를 포함한다.
본원에 사용된 바와 같이 "폴리뉴클레오티드"는 하나 또는 이중 사슬 DNA 분자 또한 RNA 분자를 의미한다. 상기 용어는 게놈 DNA, cDNA, hnRNA, mRNA 또한 이러한 분자 종의 자연적으로 발생하는 또는 인공적으로 변형된 유도체를 포함한다. 폴리뉴클레오티드는 일 실시형태에서 선형 또는 환상 분자일 수 있다. 또한, 상기 신경독 폴리펩티드를 인코딩하는 핵산 서열 이외에, 본 발명의 폴리뉴클레오티드는 적당한 전사 및/또는 번역에 필요한 추가의 서열, 예를 들면 5' 또는 3'UTR 서열을 포함할 수 있다. 본 발명의 폴리뉴클레오티드는 보툴리눔 신경독의 항원적으로 다른 항원형, 즉 BoNT/A, BoNT/B, BoNT/C1, BoNT/D, BoNT/E, BoNT/F, BoNT/G 또는 파상풍 신경독(TeNT)의 하나로부터 유도 가능한 변형된 신경독 폴리펩티드를 인코딩한다. 본 발명의 형태에서, 상기 폴리뉴클레오티드는 SEQ ID NO: 1 (BoNT/A), SEQ ID NO: 3 (BoNT/B), SEQ ID NO: 5 (BoNT/C1), SEQ ID NO: 7 (BoNT/D), SEQ ID NO: 9 (BoNT/E), SEQ ID NO: 11 (BoNT/F), SEQ ID NO: 13 (BoNT/G) 또는 SEQ ID NO: 15 (TeNT)에 나타낸 핵산 서열을 포함한다. 또한, 일 형태에서 SEQ ID NO: 2 (BoNT/A), SEQ ID NO: 4 (BoNT/B), SEQ ID NO: 6 (BoNT/C1), SEQ ID NO: 8 (BoNT/D), SEQ ID NO: 10 (BoNT/E), SEQ ID NO: 12 (BoNT/F), SEQ ID NO: 14 (BoNT/G) 또는 SEQ ID NO: 16 (TeNT)의 어느 하나에 나타낸 아미노산 서열을 인코딩하는 핵산 서열을 포함한 폴리뉴클레오티드를 포함한다. 또 다른 형태에서, 상기 폴리뉴클레오티드는 하나 이상의 뉴클레오티드 치환, 결실 및/또는 추가를 포함한 상기 폴리뉴클레오티드의 변형이다. 또한, 본 발명의 변형 폴리뉴클레오티드는 SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13 또는 15의 어느 하나에 나타낸 핵산 서열과 적어도 40%, 적어도 50%, 적어도 60%, 적어도 70%, 적어도 75%, 적어도 80%, 적어도 85%, 적어도 90%, 적어도 95%, 적어도 98% 또는 적어도 99% 동일한 핵산 서열 변형, 또는 SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 또는 16의 어느 하나에 나타낸 아미노산 서열과 적어도 40%, 적어도 50%, 적어도 60%, 적어도 70%, 적어도 75%, 적어도 80%, 적어도 85%, 적어도 90%, 적어도 95%, 적어도 98% 또는 적어도 99% 동일한 핵산 서열 변형을 포함한다. 본원에 사용된 "동일한"은 서열이 배열되어 가장 높은 차수 매치가 얻어지는, 2개의 핵산 서열 또는 아미노산 서열 사이에서 동일한 아미노산의 수를 결정하는 것을 특징으로 하는 서열 동일성을 의미한다. 예를 들면, BLASTP, BLASTN 또는 FASTA (Altschul 1990, J Mol Biol 215, 403)와 같은 컴퓨터 프로그램에서 코딩된 공개된 기술 또는 방법을 사용해서 산출될 수 있다. 동일성 값은 일 형태에서 전체의 아미노산 서열에 걸쳐서 산출된다. 다양한 알고리즘에 기초한 일련의 프로그램은 다른 서열과 비교하기 위해서 당업자에게 이용가능하다. 본 발명의 점에서, Needleman and Wunsch or Smith and Waterman의 알고리즘은 특히 신뢰할만한 결과를 제공한다. 서열 배열을 실시하기 위해서, GCG software packet (Genetics Computer Group 1991, 575 Science Drive, Madison, Wisconsin, USA 53711)의 일부인, 프로그램 PileUp (Higgins 1989, CABIOS 5, 151) 또는 프로그램 Gap and BestFit (Needleman 1970, J Mol Biol 48; 443; Smith 1981, Adv Appl Math 2, 482)이 사용될 수 있다. 상기 인용된 서열 동일성 값(%)은 본 발명의 또 다른 형태에서 전체의 영역에 대해서 하기와 같이 셋팅된 프로그램 GAP를 사용하여 결정되고, 달리 기재되어 있지 않으면 서열 배열의 표준 셋팅으로 사용될 것이다: Gap Weight: 50, Length Weight: 3, Average Match: 10.000 및 Average Mismatch: 0.000.
일 형태에서, 상기 변형 폴리뉴클레오티드의 각각은 하나 이상, 또 다른 형태에서 각각의 신경독 폴리펩티드의 모든 생물학적 특성, 즉 BoNT/A, BoNT/B, BoNT/C1, BoNT/D, BoNT/E, BoNT/F, BoNT/G 또는 파상풍 신경독 (TeNT)를 유지하는 폴리펩티드를 인코딩한다. 당업자에게 미처리된 전구체가 일부 생물학적 기능을 발휘하거나 또는 부분적으로 활성화될 수 있다고 생각될 수 있지만, 충분한 생물학적 활성은 단백질 분해 활성 후에 유지되는 것을 알 수 있다. 본원에 사용된 "생물학적 특성"은 (a) 수용체 결합, (b) 내면화, (c) 엔도솜 멤브레인 전체에서 시토솔(cytosol)로 이동 및/또는 (d) 시냅스의 소포 멤브레인 융합에 수반된 단백질의 세포내 단백질분해 절단을 의미한다. 생물학적 활성을 분석하기 위한 생체내 분석은 Pearce 등의 (Pearce 1994, Toxicol Appl Pharmacol 128: 69-77) 및 Dressler 등의 (Dressler 2005, Mov Disord 20:1617-1619, Keller 2006, Neuroscience 139: 629-637)에 기재된 생체외 생쥐의 편측횡격막 분석 및 생쥐의 LD50 분석을 포함한다. 생물학적 활성은 일반적으로 생쥐 유닛(MU)로 나타낸다. 본원에 사용된 바와 같이, 1MU는 복강내 주입후 특정한 생쥐의 개체수 50%를 죽이는 신경독 성분의 양, 즉 생쥐 i.p. LD50이다. 다른 형태에서, 변형 폴리뉴클레오티드는 개선된 또는 변경된 생물학적 특성을 갖는 신경독을 인코딩하고, 예를 들면 효소 인식에 대해서 개선된 절단 부위를 포함하거나 수용체 결합 또는 상기 기재된 다른 임의의 특성일 수 있다. 검출성 마커 펩티드 또는 태크를 포함한 융합 폴리펩티드를 포함한다. 형태에서, 적당한 태그는 FLAG-태크, Myc-태그 또는 His-태그이고, 이는 태그된 폴리펩티드를 효율적으로 정제한다. 일 형태에서, 검출성 마커 펩티드는 예를 들면 GFP, BFP 등과 같은 형광 단백질을 포함한다. 다른 형태에서, 변형 폴리뉴클레오티드는 다른 항원형, 예를 들면 중쇄 BONT/A 및 경쇄 BoNT/E를 포함한 융합 신경독의 적어도 2개의 신경독 폴리펩티드의 일부를 포함한 융합 신경독 폴리펩티드를 인코딩한다.
본 발명의 폴리뉴클레오티드에 의해서 인코딩된 신경독 폴리펩티드는 경쇄에서 적어도 하나의 분해 신호를 포함한다. 본 발명의 형태에서, 본 발명의 폴리뉴클레오티드에 의해서 인코딩된 신경독 폴리펩티드의 경쇄는 상기 특이한 핵산 서열 또는 그 변형의 어느 하나를 포함한 폴리뉴클레오티드에 의해서 인코딩된 경쇄로부터의 변형에 의해서 얻어진다. 신경독 폴리펩티드의 경쇄는 전구체 폴리펩티드(경쇄 폴리펩티드)의 단백질 분해적 절단에 의해서 발생한다. 경쇄는 단백질 분해적 절단의 결과로서 얻어진 전구체 폴리펩티드의 N-말단 부분이다. 상기 기재된 신경독 폴리펩티드의 경쇄의 아미노산 서열은 하기의 표에서 나타낸 절단 부위로부터 추론될 수 있다.
신경독
(세균 변종) |
Accession number | 절단 부위 | 절단 부위(강조)를 포함한 서열 |
BoNT/A (Hall/62A) | ABD 65472 | K428/T429 K448/A449 |
KLLCVRGIITSKTKSLDKGYNKALN....DLCIKV (SEQ ID NO: 17) |
BoNT/B (Okra) | BAE 48264 | K441/A442 | IQMCKSVKAPG...................ICIDV (SEQ ID NO: 18) |
BoNT/C1 (C-6814) | BAA 89713 | R444/S445 K449/T450 |
TKFCHKAIDGRSL....YNKTL......DCRELLV (SEQ ID NO: 19) |
BoNT/D | BAA 90661 | K442/N443 R445/D446 |
TKVCLRLTK.........NSRD......DSTCIKV (SEQ ID NO: 20) |
BoNT/E (Beluga) | CAA 43999 | K419/G420 R422/K423 |
IRFCKNIVSVKG......IRK........SICIEI (SEQ ID NO: 21) |
BoNT/F (NCTC10281) | CAA 73972 | R435/K436 K439/A440 |
VKFCKSVIPRKG......TKAP......PRLCIRV (SEQ ID NO: 22) |
BoNT/G | CAA 52275 | IAMCKPVMYKNT......GKS........EQCIIV (SEQ ID NO: 23) |
|
TeNT | P 04958 | R449 (R455) | IGLCKKIIPPTNIRENLYNRTASLTDLGGELCIKI (SEQ ID NO: 24) |
본원에 사용된 "분해 신호"는 신경독이 적용된 유기체에서 존재한 내생적인 분해 경로에 의해서 신경독 폴리펩티드의 분해를 증가시킨 신경독 폴리펩티드의 경쇄의 변형을 의미한다. 일 형태에서, 분해 경로는 프로테아솜 분해 경로 또는 리소솜 분해 경로일 것이다. 또 다른 형태에서, 분해 경로는 예를 들면 하나 이상의 단백질 분해적 절단 단계에 의해서 신경독 폴리펩티드의 부분적인 분해를 일으킬 수 있다. 상기 분해 신호는 경쇄에 도입되고(즉, 경쇄 내에서 (내부에) 위치되고), 또는 N- 또는 C-말단에 연결될 수 있다. 당업자는 적당한 분해 신호, 및 이들을 신경독 폴리펩티드의 경쇄에 도입하거나 연결하는 방법을 알 수 있다. 또한, 당업자는 재조합 분자의 생물학적 방법 또는 화학적 변형을 적용함으로써 이러한 신경독 폴리펩티드를 적어도 하나의 분해 신호로 인코딩한 폴리뉴클레오티드를 발생시킬 수 있다. 예를 들면, 부위 특이적인 돌연변이는 하기에 관한 분해 신호를 도입하기 위해서 사용할 수 있다. 또한, 신경독 폴리펩티드 및 상정된 분해 신호의 코딩 서열을 포함한 폴리뉴클레오티드의 핵산 서열이 설계되고, 전체의 폴리뉴클레오티드는 화학적으로 합성될 수 있다.
일 형태에서, 상기 분해 신호는 하기의 군으로부터 선택된다:
a) 적어도 하나의 내부에 또는 말단에 도입된 PEST 모티프 (motifs),
b) 적어도 하나의 내부에 또는 말단에 도입된 E3 리가아제 인식 모티프
c) N-말단 올리고-리신 잔기,
d) N-말단에 결합된 결합 유비퀴틴
e) N-말단 프롤린을 염기성 아미노산으로 치환
f) 표면-존재한 아미노산 잔기를 리신으로 치환,
g) 표면-존재한 아미노산 잔기를 리신으로 치환하는 것과 함께 N-말단 프롤린을 염기성 아미노산으로 치환
일 형태에서, E3 리가아제 인식 모티프는 하기의 표에서 나타낸 바와 같은 공통 서열을 갖는다(여기서, "X"는 천연 발생 아미노산의 어느 하나를 나타낼 수 있다)
E3 유비퀴틴 리가아제 | 인식 모티프 (consensus) |
VBCCul2 | ALAPYIP (SEQ ID NO: 25) |
MNM2 | RFMDYWEGL (SEQ ID NO: 26) FXXXLWXXL (SEQ ID NO: 27) |
Smurf2 | ELESPPPPYSRYPM (SEQ ID NO: 28) |
RN181 | KVGFFKR (SEQ ID No: 29) |
E3alpha | LLVRGRTLVV (SEQ ID NO 30 |
SCF | DRHDSGLDSM (SEQ ID NO: 31) |
Siah | PXAXVXP (SEQ ID NO: 32) |
Itch | PPXYXXM (SEQ ID NO: 33) |
Nedd4-2 | PPXY (SEQ ID No: 34) |
분해 신호로서 PEST 모티프가 공지되어 있다(Rogers 1986, Science 234: 364-368, Rechsteiner 1996, TIBS 21: 267-271, Belizario 2008, Science 9: 210-220). 일 형태에서, PEST 모티프는 이러한 단백질, GCN4, IκBα, Fos, Ornithine decarboxylase, Cactus, CLN2, CLN 3 또는 NIMA의 어느 하나에 대해서 Rechsteiner 1996, TIBS 21: 267-271, 표 1 (여기에 참조로서 혼입됨)에 개시된 서열을 갖는다.
본 발명의 폴리뉴클레오티드에 의해서 인코딩된 변형된 신경독 폴리펩티드는 변형되지 않은 신경독 폴리펩티드에 비해서 투여시에 피험자 내에 생물학적 효과의 기간을 감소시킬 것이다. 일 형태에서, 피험자에서 관찰된 상기 생물학적 효과는 근육 마비, 즉 (가역성) 근육의 수축능력의 불활성화를 일으킨다. 일 형태에서, 상기 작용은 소위 생쥐의 흐름 분석(running assay)(Keller 2006, Neuroscience 139: 629-637)에 의해서 시험될 수 있다. 생물학적 효과는 당업자에 의해서 더 이상 지체 없이 결정될 수 있다. 일 형태에서, 생물학적 효과 감소 기간은 통계적으로 상당히 감소된 기간을 의미한다. 작용의 기간이 통계적으로 상당히 감소된 경우, 표준 통계 시험을 적용함으로써 당업자에 의해서 결정될 수 있고, 예를 들면 신뢰도 간격, p-값 결정, 스튜던트 t-시험, MannWhitney 시험 등의 결정을 들 수 있다. 바람직한 신뢰도 간격은 적어도 90%, 적어도 95%, 적어도 97%, 적어도 98% 또는 적어도 99 %이다. p값은 바람직하게 0.1, 0.05, 0.01, 0.005, 또는 0.0001이다. 바람직하게, 본 발명에 의해서 예상된 가능성은 진단이 소정의 무리 또는 개체의 피험자의 적어도 60%, 적어도 70%, 적어도 80%, 또는 적어도 90% 에 대해서 정확할 것이다. 일 형태에서, 상기 감소된 기간은 정상 기간의 75% 미만, 70% 미만, 65% 미만, 60% 미만, 55% 미만, 50% 미만, 45% 미만, 40% 미만, 30% 미만 또는 20% 미만, 즉 미변형된 신경독 폴리펩티드에 대해서 관찰된 기간을 지속한다. 일 형태에서, 일반적인 기간은 BoNT/A의 경우에 대략 4개월, BoNT/B의 경우에 2 개월, BoNT/C의 경우에 대략 3내지 4개월, 또는 BoNT/E의 경우에 대략 4주 지속한다. (Foran, J Biol. Chem. 278(2): 1363-1371, Eleopra 1998, Neurosci Lett. 13, 256(3): 135-138, Eleopra 1997, Neurosci Lett. 14,224(2): 91-94, Sloop 1997, Neurology 49(1): 189-194, Washbourne 1998, J Physiol Paris 92(2): 135-139). 작용의 기간은 피험자 내에 개개의 영향, 예를 들면 유전적인 배경, 나이, 라이프스타일, 등에 의존한 것을 이해한다. 따라서, 본원에 의미하는 대략 기간은 25% 이하, 20% 이하, 15% 이하, 10 % 이하 또는 5% 이하의 표준 편차와 함께, 각각의 신경독 폴리펩티드에 대해서 상기 나타낸 바와 같은 기간을 의미한다.
바람직하게, 본 발명에 따라서 신경독 폴리펩티드는 투여시 피험자내에 생물학적 효과가 감소되도록 변형될 수 있는 것을 알 수 있다. 주로, 이는 경쇄의 지속이 생물학적 효과 기간과 관련된 것을 알 수 있기 때문에, 상기 신경독 폴리펩티드의 경쇄에 분해 신호를 도입하거나 결합함으로써 달성될 수 있다. 신경독 폴리펩티드에 의해서 도출된 생물학적 효과의 감소된 기간은 상처 치유를 용이하게 하기 위해서 신경 작용의 불활성, 예를 들면 근육 마비를 필요로 하는 다양한 의학적 적용에 유익하다.
본 발명은 본 발명의 폴리뉴클레오티드를 포함한 벡터에 관한 것이다.
"벡터"는 바람직하게 파지, 플라스미드, 바이러스 또는 레트로바이러스 벡터, 또한 인공적 크로모솜, 예를 들면 세균 또는 이스트 인공적 크로모솜을 포함한다. 또한, 상기 용어는 목적 구성을 게놈 DNA에 랜덤 또는 부위 특이적으로 통합시키는 목적 구성에 관한 것이다. 이러한 목적 구성은 바람직하게 하기 기재된 바와 같이 동종 또는 이종 재조합의 충분한 길이의 DNA를 포함한다. 일 형태에서 본 발명의 폴리뉴클레오티드를 포함한 벡터는 숙주에서 증식 및/또는 선택에 대한 선택성 마커를 포함한다. 벡터는 공지된 다양한 방법에 의해서 숙주 세포에 포함될 수 있다. 예를 들면, 플라스미드 벡터는 칼슘 포스페이트 석출물 또는 루비듐 클로라이드 석출물과 같은 석출물, 또는 충전된 리피드와 복합물 또는 탄소계 클러스터, 예를 들면 플러렌에서 도입될 수 있다. 또한, 플라스미드 벡터는 가열 충격 또는 전기천공법에 의해서 도입될 수 있다. 벡터가 바이러스이면, 숙주 세포에 적용하기 전에 적당한 패키징 세포 라인을 사용해서 실험관에서 패키징될 수 있다. 레트로바이러스는 복제 가능하거나 복제 결함일 수 있다. 후자의 경우에, 바이러스 증식은 일반적으로 상보적인 숙주/세포에서 발생할 수 있다. 또한, 본 발명의 형태에서, 폴리뉴클레오티드는 상기 벡터에서 진핵 또는 원핵 숙주 세포 또는 그 독립된 분획에서 발현하는 발현 제어 서열에 조작적으로 결합된다. 폴리뉴클레오티드의 발현은 폴리뉴클레오티드를 번역 가능한 mRNA로의 전사를 포함한다. 숙주 세포에서 발현을 보장하는 조절 요소가 공지되어 있다. 일 형태에서, 이들은 전사의 개시를 보장하는 조절 배열 및/또는 전사의 종결 및 전사 산물의 안정화를 보장하는 폴리-A 신호를 포함한다. 추가의 조절 요소는 잔사 또한 번역 인핸서를 포함할 수 있다. 원핵생물 숙주 세포에서 발현 가능한 조절 요소는, 예를 들면 E.coli에서 lac-, trp- 또는 tac- 촉진제를 포함하고, 진핵생물 숙주 세포에서 발현을 허가하는 조절 요소는 이스트에서 AOXl- 또는 GAL1 촉진제이고 또는 CMV-, SV40, RSV- 프로모터(Rous sarcoma virus), CMV-인핸서, SV40-인핸서 또는 포유류 또는 다른 동물 세포에서 글로빈 인트론이다. 또한, 유도되는 발현 대조 서열은 본 발명에 의해서 포함된 발현 벡터에 사용될 수 있다. 이러한 유도 가능한 벡터는 tet 또는 lac 조작자 서열, 또는 열 충격 또는 다른 환경 요소에 의해서 유도 가능한 서열을 포함할 수 있다. 적당한 발현 대조 서열이 공지되어 있다. 전사의 개시에 기인한 요소 이외에, 이러한 조절 요소는 전사 말단 신호, 예를 들면 SV40-poly-A 부위 또는 tk-poly-A 부위, 폴리펩티드 하부 흐름을 포함할 수 있다. 본 발명에서, 적당한 발현 벡터는 예를 들면 Okayama-Berg cDNA 발현 벡터 pcDV1 (Pharmacia), pBluescript (Stratagene), pCDM8, pRc/CMV, pcDNA1, pcDNA3 (Invitrogen) 또는 pSPORT1가 알려져 있다. 바람직하게, 상기 벡터는 발현 벡터 및 유전자 전달 또는 목적의 벡터이다. 발현 벡터는 바이러스, 예를 들면 레트로바이러스, 백신 바이러스, 아데노 관련 바이러스, 헤르페스 바이러스 또는 소 유두종 바이러스로부터 유래된 발현 벡터는 본 발명의 벡터 또는 폴리뉴클레오티드를 목적의 세포 개체로의 전달에서 사용될 수 있다. 당업자에게 공지된 방법은 재조합 바이러스 벡터를 구성하기 위해서 사용될 수 있다; 예를 들면, Sambrook, Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory (1989) N.Y. and Ausubel, Current Protocols in Molecular Biology, Green Publishing Associates and Wiley Interscience, N.Y. (1994)에 기재된 방법을 참조한다.
또한, 본 발명은 본 발명의 폴리뉴클레오티드 또는 벡터를 포함한 숙주 세포에 관한 것이다.
본원에 사용된 "숙주 세포"는 진핵세포 및 원핵 숙주 세포를 포함한다. 일 형태에서 숙주 세포는 세균성 세포이고, 또 다른 형태에서 피르미쿠트 세균 세포이다. 일 형태에서, 상기 세균성 숙주 세포는 대장균 숙주 세포이다. 또 다른 형태에서, 클로스트리디움 숙주 세포이다. 또 다른 형태에서, 상기 클로스트리디움 숙주 세포는 보툴리눔균 숙주 세포이고, 또 다른 형태에서 보툴리눔균의 7개의 다른 항원형 중 하나의 세포이다. 또 다른 형태에서, 세균성 숙주 세포는 파상풍균 숙주 세포이다. 또 다른 형태에서, 숙주 세포는 바실러스 숙주 세포이고, 특히 바실러스 마그테리움 숙주 세포이다. 진핵 숙주 세포는 이스트 숙주 세포와 같은 균류 숙주 세포 또는 독성 단백질의 제조에 적합한 동물 세포주의 세포이다.
본 발명은 본 발명의 플리뉴클레오티드에 의해서 인코딩된 폴리펩티드를 포함한다.
본원에 사용된 "폴리펩티드"는 숙주 세포의 복합 단백질 (HA70, HA17, HA33, 또는 NTNH (NBP))을 포함하는, 다른 폴리펩티드가 필수적으로 없는, 분리되거나 본질적으로 정제된 폴리펩티드 또는 부가적으로 다른 단백질을 포함한 폴리펩티드 제제 (polypeptide preparations)를 포함한다. 또한, 용어는 화학적으로 변경된 폴리펩티드를 포괄한다. 이러한 변형은 인공적인 변형 또는 자연적으로 발생한 변형일 수 있다. 상기 기재된 바와 같이, 본 발명의 폴리펩티드는 상기 기재된 신경독 폴리펩티드의 생물학적 특성을 가질 수 있다. 또한, 투여시에 피험자에서 생물학적 효과의 기간이 감소시킬 수 있다. 일 형태에서, 본 발명의 폴리펩티드는 보다 상세하게 본원에 기재된 바와 같이 폴리펩티드의 제조방법에 의해서 제조될 수 있다. 본 발명의 형태에서, 폴리펩티드 제제는 신경독 폴리펩티드의 복합물 및 그 복합 단백질을 포함한 것이 예상된다.
또한, 본 발명은 본 발명의 폴리펩티드에 특이적으로 결합한 항체에 관한 것이다.
본 발명의 폴리펩티드에 대한 항체는 항원으로서 본 발명에 따른 정제된 폴리펩티드 또는 유도된 적합한 단편을 사용해서 공지된 방법에 의해서 제조될 수 있다. 항원으로서 적합한 단편은 공지된 항원성-결정 알고리즘에 의해서 식별될 수 있다. 이러한 단편은 단백질 분해에 의해서 본 발명의 폴리펩티드로부터 얻어지거나 또는 합성 펩티드일 수 있다. 일 형태에서, 본 발명의 항체는 모노클로날 항체, 폴리클로날 항체, 단쇄 항체, 인간 또는 인간화 항체 또는 성숙화, 또는 키메라 항체 또는 그 단편이다. 본 발명에 의한 항체로서 이중특이성, 합성 항체, 항체 단편, 예를 들면 Fab, Fv 또는 scFv 단편, 등 또는 이들 단편의 화학적으로 변형 유도체를 포함한다. 본 발명의 항체는 본 발명의 폴리펩티드에 특이적으로 결합할 것이다(즉, 다른 폴리펩티드 또는 펩티드와 교차반응하지 않는다). 특이적으로, 항체는 미변형된 신경독 폴리펩티드와 교차 반응하지 않을 수 있다. 특이적 결합은 다양한 공지의 방법에 의해서 시험될 수 있다. 항체 또는 그 단편은 예를 들면 Harlow and Lane "Antibodies, A Laboratory Manual", CSH Press, Cold Spring Harbor, 1988에 기재된 방법을 사용해서 제조할 수 있다. 모노클로날 항체는 Kohler 등의 (Kohler 1975, Nature 256 (1975), 495) or Galfre(Galfre 1981, Meth. Enzymol. 73 (1981))에 기재된 방법을 사용하여 제조될 수 있다. 이는 항원, 즉 본 발명의 폴리펩티드 또는 그 면역성 항원 단편에 의해서 면역력을 갖는 포유류로부터 유도된 비장세포에 대한 생쥐의 골수종 세포의 융합을 포함한다. 항체는 본 발명의 폴리펩티드의 면역침강 및 면역학적 국재 결정, 또한 재조합 유기체에서 상기 폴리펩티드의 존재를 모니터링 및 본 발명에 따른 단백질과 상호작용하는 화합물을 식별화하는 데에 사용될 수 있다. 예를 들면, BIAcore 시스템에서 사용된 표면 플라즈몬 공명이 사용되어 본 발명의 단백질의 에피토프에 결합한 파지 항체의 효율을 증가시킬 수 있다(Schier 1996, Human Antibodies Hybridomas 7, 97-105; Malmborg 1995, J. Immunol. Methods 183, 7-13).
본 발명의 폴리뉴클레오티드 또는 폴리펩티드는 일반적으로 약제로서 사용될 수 있다.
본원에 사용된 "약제"는 일 형태에서 생물학적으로 활성 신경독 폴리펩티드를 함유한 약학적 조성물 또는 약학적 활성 화합물로서 이를 인코딩한 폴리뉴클레오티드를 의미한다. 상기 약제는 다양한 질병 또는 장애가 있는 인간 또는 동물 치료하기 위해서 치료적으로 유효한 양으로 사용될 수 있다. 약물은 소망의 적용 목적에 의존한 다양한 방법에 의해서 제형화될 수 있다. 본 발명에 따른 약제의 다른 형태가 하기에 기재된다.
일 형태에서, 약제는 약학적 조성물로서 하나 이상의 약학적으로 허용가능한 담체 (carriers)에서 본 발명의 생물학적 활성 신경독 폴리펩티드를 포함한다. 약학적 허용가능한 담체는 제형의 다른 성분과 상용가능하고 그 수용체에 유해하지 않는 점에서 허용되어야 한다. 사용된 약학적 담체는 고체, 겔 또는 액체을 포함할 수 있다. 고체 담체로는 락토오스, 테라 알바, 슈크로오스, 탈크, 겔라틴, 아가, 펙틴, 아카시아, 마그네슘 스테아레이트, 스테아르산, 등이다. 액체 담체로는 글리세롤, 인산 완충염 용액, 물, 에멀젼, 다양한 형태의 습윤제이다. 적당한 담체로는 상기 기재된 것 및 공지된 그외의 것을 포함하고, Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pennsylvania을 참조한다. 담체는 약제의 활성 성분이 본 발명의 폴리뉴클레이오티드이면 유전자 치료에 적당한 바이러스 또는 레트로바이러스일 수 있는 것으로 이해될 것이다.
일 형태에서, 약제는 투여 전에 희석액에 용해될 것이다. 희석액은 조합의 생물학적 활성에 영향을 미치지 않도록 선택된다. 이러한 희석액으로는 증류수 또는 생리적 식염수이다. 또한, 약학적 조성물 또는 제형은 다른 담체 또는 비독성, 비-치료의, 비-면역의 안정제 등을 포함할 수 있다. 따라서, 일 형태에서 본 발명의 비독성 폴리펩티드는 액체 또는 동결건조된 형태로 존재할 수 있다. 일 형태에서, 글리세롤, 단백질 안정화제(HSA) 또는 비-독성 안정화제, 예를 들면 폴리비닐피롤리돈(PVP), 히알루론산 또는 자유 아미노산과 함께 존재할 수 있다. 일 형태에서, 적당한 비-단백질 안정화제는 WO 2005/007185 또는 WO 2006/020208에 기재된다.
다른 형태에서, 약제는 신경독 폴리펩티드를 포함한 용액으로서 제공될 것이다. 또한, 용액은 상기 기재된 담체 또는 안정화제를 포함할 수 있다. 신경독 폴리펩티드의 안정한 액체 제형은 US 7,211, 261에 기재된 바와 같이 제공될 수 있다.
일 형태에서, 약학적 조성물은 경피 투여된다. 종래에 약제는 소망의 의학적 적응에 따라서 근육 내 또는 피하(샘 근방)에 투여될 수 있다. 그러나, 화합물의 상태 및 작용모드에 따라서, 약학적 조성물은 다른 경로에 의해서 투여될 수 있다.
치료적 유효량은 본 명세서에 관한 질환 또는 질병을 수반한 증상을 방지하거나, 개선하거나 치료한 본 발명의 신경독 폴리펩티드 또는 폴리뉴클레오티드의 양을 의미한다. 화합물의 치료적 효능 및 독성은 세포 배양물 또는 실험적 동물, 예를 들면 ED50(개체의 50%에서 치료적으로 유효한 양) 및 LD50(개체의 50%에 치명적인 양)에서 표준 약학적 절차에 의해서 결정될 수 있다. 치료적 및 독성 작용 사이의 투여율이 치료 지수이며, LD50/ED50로 표현될 수 있다. 본 발명의 약물은 개개의 환자에 따라서 투여 조절량을 예상하기 위해서, 처방자 또는 사용자 지시사항 내에 투여량 추천사항을 포함할 것이다.
본원에 관한 약물은 본 명세서에서 인용된 질병 또는 질환을 치료하거나 개선하거나 방지하기 위해서 적어도 1회 투여되는 것으로 개발된다. 그러나, 상기 약제는 1회 초과해서 투여될 수 있다.
또 다른 형태에서 본 발명에 따른 약제는 그 제형중에서 약학적 조성물에 첨가된 생물학적으로 활성 신경독 폴리펩티드 이외에 약물을 포함할 수 있다.
또한, 본 발명은 상처 치유, 뼈 및 힘줄 골절 치료를 위한 부동화, 구체적으로 치핵절제, 치과 임플란트 도입 또는 관절치환술(엔도프로테시스), 관절 형성, 안과 수술에 관련된 수술 후 부동화, 여드름 또는 과민성 대장 증후군의 약제를 제조하기 위해서 본 발명의 폴리뉴클레오티드 또는 폴리펩티드를 사용하는 것에 관한 것이다.
상기 질환 또는 질병에 관한 증상은 당업자에게 공지되어 있고 약물의 표준 텍스트북, 예를 들면 Stedman 또는 Pschyrembl에 기재된다.
또한, 본 발명은 피험자가 신경독 치료에 민감한지를 결정하기 위한 진단 약제를 제조하기 위해서 본 발명의 폴리뉴클레오티드 또는 폴리펩티드를 사용하는 것에 관한 것이다.
상기의 진단 약제는 상기에 기재된 신경독 폴리펩티드 약제이다. 그러나, 약제는 피험자가 적당한 투여 요법의 모두 또는 그 결정에서 신경독 폴리펩티드에 대응하는 지를 결정하는 투여요법에서 잠시 동안 적용된다. 상기 신경독 폴리펩티드는 치료 포텐셜을 갖지만, 일 형태에서 치료 또는 개선보다 차라리 진단 목적에 요긴하게 사용되기 때문에, 약제를 "진단 약제"라고 한다. 따라서, 본 발명의 변형된 신경독 폴리펩티드를 갖는 시간-제한 프리-스크린은 비-변형된 신경독을 사용한 치료에 민감한 피험자의 선택 또한 적당한 투여의 결정을 도울 수 있다. 더 긴 시간에 걸쳐서 일반적으로 지속된 비-변형된 신경독에 기초한 치료의 잠재적 부작용은 본 발명의 변형된 신경독 폴리펩티드에 의해서 유도된 생물학적 효과의 기간의 감소 때문에 감소될 수 있다.
본 발명은 하기의 단계를 포함한 본 발명의 폴리뉴클레오티드에 의해서 인코딩된 신경독 폴리펩티드의 제조에 대한 방법을 포함한다:
a) 본 발명의 폴리뉴클레오티드에 의해서 인코딩된 신경독 폴리펩티드를 발현하는 조건하에서 본 발명의 숙주 세포를 배양하는 단계, 및
b) a)의 숙주 세포 배양액으로부터 본 발명의 폴리뉴클레오티드에 의해서 인코딩된 신경독 폴리펩티드를 얻는 단계.
일 형태에서, 폴리펩티드는 친화성 크로마토그래피, 크기 배제 크로마토그래피, 고압 액체 크로마토그래피(HPLC)를 포함한 모든 종래의 정제 방법 및 항체 석출을 포함한 석출 방법에 의해서 배양물로부터 얻어질 수 있다. 또한, 일 형태에서, 본 발명의 방법에 의해서 얻어진 신경독 폴리펩티드는 복합 단백질을 함유하지 않을 수 있다. 또 다른 형태에서, 신경독 폴리펩티드는 신경독 폴리펩티드 복합 단백질을 포함한 복합물로서 얻어질 수 있다. 또한, 본원에 사용된 바와 같이, 얻어진 것은 신경독 폴리펩티드의 활성을 포함한다. 이것은 내생 또는 외인성(예를 들면 재조합 발현) 프로테아제에 의한 세포간 또는 예를 들면 상기 정제 전, 중 또는 후에 신경독 폴리펩티드를 절단시키는 조건하에서 프로테아제와 접촉에 의한 세포의 외측에 (단쇄) 신경독 폴리펩티드 전구체의 단백질 분해적 절단에 의해서 달성될 수 있다.
또한, 약제의 제조방법은 본 발명에 따르는 것으로서, 본 발명의 상기 방법의 단계 및 약제로서 본 발명의 폴리펩티드에 의해서 인코딩된 신경독 폴리펩티드를 제형하는 추가의 단계를 포함한다.
이러한 약제 제조의 방법은 품질, 약학적 안전성 및 약제 효능을 보장하기 위해서 약제의 GMP 표준에 따라서 실시된다. 약제의 적당한 제형은 이러한 명세서에 기재된다. 당업자는 이러한 제형의 제조방법을 알 수 있다.
본 발명은 본 발명의 방법의 단계 및 화장품 조성물로서 신경독 폴리펩티드를 제형하는 추가의 단계를 포함한 화장품 조성물의 제조방법을 포함한다.
본원에 사용된 "화장품 조성물"은 상기 약학적 조성물에 기재된 바와 같이 제형될 수 있다. 마찬가지로 화장품 조성물에 대해서, 본 발명의 화합물은 실질적으로 순수한 형태로 사용되는 것이 예상된다. 그러나, 불순물은 약제에 대해서 덜 중요할 수 있다. 다른 형태에서, 화장품 조성물은 근육 내에 적용될 수 있다. 본 발명의 또 다른 형태에서, 신경독을 포함한 화장품 조성물은 항주름제로서 제형화될 수 있다.
본 발명은 이러한 화장품 조성물 및 항주름제로서 사용될 화장품 조성물을 제조하기 위한 본 발명의 폴리펩티드 또는 폴리뉴클레오티드의 사용에 관한 것이다.
본 명세서의 모든 참조문헌은 전체 개시 내용 및 본 명세서에 특이적으로 언급된 개시 내용에 의해서 포함된다.
<110> Merz Pharma GmbH & Co.KGaA
<120> Neurotoxins exhibiting shortened biological activity
<130> MP66380EP
<160> 34
<170> PatentIn version 3.5
<210> 1
<211> 3891
<212> DNA
<213> Clostridium botulinum
<400> 1
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gatggtagtt atagatcaga agaacttaat ctagtaataa taggaccctc agctgatatt 480
atacagtttg aatgtaaaag ctttggacat gaagttttga atcttacgcg aaatggttat 540
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ttagcacatg aacttataca tgctggacat agattatatg gaatagcaat taatccaaat 720
agggttttta aagtaaatac taatgcctat tatgaaatga gtgggttaga agtaagcttt 780
gaggaactta gaacatttgg gggacatgat gcaaagttta tagatagttt acaggaaaac 840
gaatttcgtc tatattatta taataagttt aaagatatag caagtacact taataaagct 900
aaatcaatag taggtactac tgcttcatta cagtatatga aaaatgtttt taaagagaaa 960
tatctcctat ctgaagatac atctggaaaa ttttcggtag ataaattaaa atttgataag 1020
ttatacaaaa tgttaacaga gatttacaca gaggataatt ttgttaagtt ttttaaagta 1080
cttaacagaa aaacatattt gaattttgat aaagccgtat ttaagataaa tatagtacct 1140
aaggtaaatt acacaatata tgatggattt aatttaagaa atacaaattt agcagcaaac 1200
tttaatggtc aaaatacaga aattaataat atgaatttta ctaaactaaa aaattttact 1260
ggattgtttg aattttataa gttgctatgt gtaagaggga taataacttc taaaactaaa 1320
tcattagata aaggatacaa taaggcatta aatgatttat gtatcaaagt taataattgg 1380
gacttgtttt ttagtccttc agaagataat tttactaatg atctaaataa aggagaagaa 1440
attacatctg atactaatat agaagcagca gaagaaaata ttagtttaga tttaatacaa 1500
caatattatt taacctttaa ttttgataat gaacctgaaa atatttcaat agaaaatctt 1560
tcaagtgaca ttataggcca attagaactt atgcctaata tagaaagatt tcctaatgga 1620
aaaaagtatg agttagataa atatactatg ttccattatc ttcgtgctca agaatttgaa 1680
catggtaaat ctaggattgc tttaacaaat tctgttaacg aagcattatt aaatcctagt 1740
cgtgtttata catttttttc ttcagactat gtaaagaaag ttaataaagc tacggaggca 1800
gctatgtttt taggctgggt agaacaatta gtatatgatt ttaccgatga aactagcgaa 1860
gtaagtacta cggataaaat tgcggatata actataatta ttccatatat aggacctgct 1920
ttaaatatag gtaatatgtt atataaagat gattttgtag gtgctttaat attttcagga 1980
gctgttattc tgttagaatt tataccagag attgcaatac ctgtattagg tacttttgca 2040
cttgtatcat atattgcgaa taaggttcta accgttcaaa caatagataa tgctttaagt 2100
aaaagaaatg aaaaatggga tgaggtctat aaatatatag taacaaattg gttagcaaag 2160
gttaatacac agattgatct aataagaaaa aaaatgaaag aagctttaga aaatcaagca 2220
gaagcaacaa aggctataat aaactatcag tataatcaat atactgagga agagaaaaat 2280
aatattaatt ttaatattga tgatttaagt tcgaaactta atgagtctat aaataaagct 2340
atgattaata taaataaatt tttgaatcaa tgctctgttt catatttaat gaattctatg 2400
atcccttatg gtgttaaacg gttagaagat tttgatgcta gtcttaaaga tgcattatta 2460
aagtatatat atgataatag aggaacttta attggtcaag tagatagatt aaaagataaa 2520
gttaataata cacttagtac agatatacct tttcagcttt ccaaatacgt agataatcaa 2580
agattattat ctacatttac tgaatatatt aagaatatta ttaatacttc tatattgaat 2640
ttaagatatg aaagtaatca tttaatagac ttatctaggt atgcatcaaa aataaatatt 2700
ggtagtaaag taaattttga tccaatagat aaaaatcaaa ttcaattatt taatttagaa 2760
agtagtaaaa ttgaggtaat tttaaaaaat gctattgtat ataatagtat gtatgaaaat 2820
tttagtacta gcttttggat aagaattcct aagtatttta acagtataag tctaaataat 2880
gaatatacaa taataaattg tatggaaaat aattcaggat ggaaagtatc acttaattat 2940
ggtgaaataa tctggacttt acaggatact caggaaataa aacaaagagt agtttttaaa 3000
tacagtcaaa tgattaatat atcagattat ataaacagat ggatttttgt aactatcact 3060
aataatagat taaataactc taaaatttat ataaatggaa gattaataga tcaaaaacca 3120
atttcaaatt taggtaatat tcatgctagt aataatataa tgtttaaatt agatggttgt 3180
agagatacac atagatatat ttggataaaa tattttaatc tttttgataa ggaattaaat 3240
gaaaaagaaa tcaaagattt atatgataat caatcaaatt caggtatttt aaaagacttt 3300
tggggtgatt atttacaata tgataaacca tactatatgt taaatttata tgatccaaat 3360
aaatatgtcg atgtaaataa tgtaggtatt agaggttata tgtatcttaa agggcctaga 3420
ggtagcgtaa tgactacaaa catttattta aattcaagtt tgtatagggg gacaaaattt 3480
attataaaaa aatatgcttc tggaaataaa gataatattg ttagaaataa tgatcgtgta 3540
tatattaatg tagtagttaa aaataaagaa tataggttag ctactaatgc atcacaggca 3600
ggcgtagaaa aaatactaag tgcattagaa atacctgatg taggaaatct aagtcaagta 3660
gtagtaatga agtcaaaaaa tgatcaagga ataacaaata aatgcaaaat gaatttacaa 3720
gataataatg ggaatgatat aggctttata ggatttcatc agtttaataa tatagctaaa 3780
ctagtagcaa gtaattggta taatagacaa atagaaagat ctagtaggac tttgggttgc 3840
tcatgggaat ttattcctgt agatgatgga tggggagaaa ggccactgta a 3891
<210> 2
<211> 3661
<212> PRT
<213> Clostridium botulinum
<400> 2
Met Glu Thr Pro Arg Pro His Glu Val Ala Leu Ala Ser Asn Leu Tyr
1 5 10 15
Ser Gly Leu Asn Pro His Glu Ala Ser Asn Thr Tyr Arg Leu Tyr Ser
20 25 30
Ala Ser Pro Pro Arg Val Ala Leu Ala Ser Asn Gly Leu Tyr Val Ala
35 40 45
Leu Ala Ser Pro Ile Leu Glu Ala Leu Ala Thr Tyr Arg Ile Leu Glu
50 55 60
Leu Tyr Ser Ile Leu Glu Pro Arg Ala Ser Asn Ala Leu Ala Gly Leu
65 70 75 80
Tyr Gly Leu Asn Met Glu Thr Gly Leu Asn Pro Arg Val Ala Leu Leu
85 90 95
Tyr Ser Ala Leu Ala Pro His Glu Leu Tyr Ser Ile Leu Glu His Ile
100 105 110
Ser Ala Ser Asn Leu Tyr Ser Ile Leu Glu Thr Arg Pro Val Ala Leu
115 120 125
Ile Leu Glu Pro Arg Gly Leu Ala Arg Gly Ala Ser Pro Thr His Arg
130 135 140
Pro His Glu Thr His Arg Ala Ser Asn Pro Arg Gly Leu Gly Leu Gly
145 150 155 160
Leu Tyr Ala Ser Pro Leu Glu Ala Ser Asn Pro Arg Pro Arg Pro Arg
165 170 175
Gly Leu Ala Leu Ala Leu Tyr Ser Gly Leu Asn Val Ala Leu Pro Arg
180 185 190
Val Ala Leu Ser Glu Arg Thr Tyr Arg Thr Tyr Arg Ala Ser Pro Ser
195 200 205
Glu Arg Thr His Arg Thr Tyr Arg Leu Glu Ser Glu Arg Thr His Arg
210 215 220
Ala Ser Pro Ala Ser Asn Gly Leu Leu Tyr Ser Ala Ser Pro Ala Ser
225 230 235 240
Asn Thr Tyr Arg Leu Glu Leu Tyr Ser Gly Leu Tyr Val Ala Leu Thr
245 250 255
His Arg Leu Tyr Ser Leu Glu Pro His Glu Gly Leu Ala Arg Gly Ile
260 265 270
Leu Glu Thr Tyr Arg Ser Glu Arg Thr His Arg Ala Ser Pro Leu Glu
275 280 285
Gly Leu Tyr Ala Arg Gly Met Glu Thr Leu Glu Leu Glu Thr His Arg
290 295 300
Ser Glu Arg Ile Leu Glu Val Ala Leu Ala Arg Gly Gly Leu Tyr Ile
305 310 315 320
Leu Glu Pro Arg Pro His Glu Thr Arg Pro Gly Leu Tyr Gly Leu Tyr
325 330 335
Ser Glu Arg Thr His Arg Ile Leu Glu Ala Ser Pro Thr His Arg Gly
340 345 350
Leu Leu Glu Leu Tyr Ser Val Ala Leu Ile Leu Glu Ala Ser Pro Thr
355 360 365
His Arg Ala Ser Asn Cys Tyr Ser Ile Leu Glu Ala Ser Asn Val Ala
370 375 380
Leu Ile Leu Glu Gly Leu Asn Pro Arg Ala Ser Pro Gly Leu Tyr Ser
385 390 395 400
Glu Arg Thr Tyr Arg Ala Arg Gly Ser Glu Arg Gly Leu Gly Leu Leu
405 410 415
Glu Ala Ser Asn Leu Glu Val Ala Leu Ile Leu Glu Ile Leu Glu Gly
420 425 430
Leu Tyr Pro Arg Ser Glu Arg Ala Leu Ala Ala Ser Pro Ile Leu Glu
435 440 445
Ile Leu Glu Gly Leu Asn Pro His Glu Gly Leu Cys Tyr Ser Leu Tyr
450 455 460
Ser Ser Glu Arg Pro His Glu Gly Leu Tyr His Ile Ser Gly Leu Val
465 470 475 480
Ala Leu Leu Glu Ala Ser Asn Leu Glu Thr His Arg Ala Arg Gly Ala
485 490 495
Ser Asn Gly Leu Tyr Thr Tyr Arg Gly Leu Tyr Ser Glu Arg Thr His
500 505 510
Arg Gly Leu Asn Thr Tyr Arg Ile Leu Glu Ala Arg Gly Pro His Glu
515 520 525
Ser Glu Arg Pro Arg Ala Ser Pro Pro His Glu Thr His Arg Pro His
530 535 540
Glu Gly Leu Tyr Pro His Glu Gly Leu Gly Leu Ser Glu Arg Leu Glu
545 550 555 560
Gly Leu Val Ala Leu Ala Ser Pro Thr His Arg Ala Ser Asn Pro Arg
565 570 575
Leu Glu Leu Glu Gly Leu Tyr Ala Leu Ala Gly Leu Tyr Leu Tyr Ser
580 585 590
Pro His Glu Ala Leu Ala Thr His Arg Ala Ser Pro Pro Arg Ala Leu
595 600 605
Ala Val Ala Leu Thr His Arg Leu Glu Ala Leu Ala His Ile Ser Gly
610 615 620
Leu Leu Glu Ile Leu Glu His Ile Ser Ala Leu Ala Gly Leu Tyr His
625 630 635 640
Ile Ser Ala Arg Gly Leu Glu Thr Tyr Arg Gly Leu Tyr Ile Leu Glu
645 650 655
Ala Leu Ala Ile Leu Glu Ala Ser Asn Pro Arg Ala Ser Asn Ala Arg
660 665 670
Gly Val Ala Leu Pro His Glu Leu Tyr Ser Val Ala Leu Ala Ser Asn
675 680 685
Thr His Arg Ala Ser Asn Ala Leu Ala Thr Tyr Arg Thr Tyr Arg Gly
690 695 700
Leu Met Glu Thr Ser Glu Arg Gly Leu Tyr Leu Glu Gly Leu Val Ala
705 710 715 720
Leu Ser Glu Arg Pro His Glu Gly Leu Gly Leu Leu Glu Ala Arg Gly
725 730 735
Thr His Arg Pro His Glu Gly Leu Tyr Gly Leu Tyr His Ile Ser Ala
740 745 750
Ser Pro Ala Leu Ala Leu Tyr Ser Pro His Glu Ile Leu Glu Ala Ser
755 760 765
Pro Ser Glu Arg Leu Glu Gly Leu Asn Gly Leu Ala Ser Asn Gly Leu
770 775 780
Pro His Glu Ala Arg Gly Leu Glu Thr Tyr Arg Thr Tyr Arg Thr Tyr
785 790 795 800
Arg Ala Ser Asn Leu Tyr Ser Pro His Glu Leu Tyr Ser Ala Ser Pro
805 810 815
Ile Leu Glu Ala Leu Ala Ser Glu Arg Thr His Arg Leu Glu Ala Ser
820 825 830
Asn Leu Tyr Ser Ala Leu Ala Leu Tyr Ser Ser Glu Arg Ile Leu Glu
835 840 845
Val Ala Leu Gly Leu Tyr Thr His Arg Thr His Arg Ala Leu Ala Ser
850 855 860
Glu Arg Leu Glu Gly Leu Asn Thr Tyr Arg Met Glu Thr Leu Tyr Ser
865 870 875 880
Ala Ser Asn Val Ala Leu Pro His Glu Leu Tyr Ser Gly Leu Leu Tyr
885 890 895
Ser Thr Tyr Arg Leu Glu Leu Glu Ser Glu Arg Gly Leu Ala Ser Pro
900 905 910
Thr His Arg Ser Glu Arg Gly Leu Tyr Leu Tyr Ser Pro His Glu Ser
915 920 925
Glu Arg Val Ala Leu Ala Ser Pro Leu Tyr Ser Leu Glu Leu Tyr Ser
930 935 940
Pro His Glu Ala Ser Pro Leu Tyr Ser Leu Glu Thr Tyr Arg Leu Tyr
945 950 955 960
Ser Met Glu Thr Leu Glu Thr His Arg Gly Leu Ile Leu Glu Thr Tyr
965 970 975
Arg Thr His Arg Gly Leu Ala Ser Pro Ala Ser Asn Pro His Glu Val
980 985 990
Ala Leu Leu Tyr Ser Pro His Glu Pro His Glu Leu Tyr Ser Val Ala
995 1000 1005
Leu Leu Glu Ala Ser Asn Ala Arg Gly Leu Tyr Ser Thr His Arg Thr
1010 1015 1020
Tyr Arg Leu Glu Ala Ser Asn Pro His Glu Ala Ser Pro Leu Tyr Ser
1025 1030 1035 1040
Ala Leu Ala Val Ala Leu Pro His Glu Leu Tyr Ser Ile Leu Glu Ala
1045 1050 1055
Ser Asn Ile Leu Glu Val Ala Leu Pro Arg Leu Tyr Ser Val Ala Leu
1060 1065 1070
Ala Ser Asn Thr Tyr Arg Thr His Arg Ile Leu Glu Thr Tyr Arg Ala
1075 1080 1085
Ser Pro Gly Leu Tyr Pro His Glu Ala Ser Asn Leu Glu Ala Arg Gly
1090 1095 1100
Ala Ser Asn Thr His Arg Ala Ser Asn Leu Glu Ala Leu Ala Ala Leu
1105 1110 1115 1120
Ala Ala Ser Asn Pro His Glu Ala Ser Asn Gly Leu Tyr Gly Leu Asn
1125 1130 1135
Ala Ser Asn Thr His Arg Gly Leu Ile Leu Glu Ala Ser Asn Ala Ser
1140 1145 1150
Asn Met Glu Thr Ala Ser Asn Pro His Glu Thr His Arg Leu Tyr Ser
1155 1160 1165
Leu Glu Leu Tyr Ser Ala Ser Asn Pro His Glu Thr His Arg Gly Leu
1170 1175 1180
Tyr Leu Glu Pro His Glu Gly Leu Pro His Glu Thr Tyr Arg Leu Tyr
1185 1190 1195 1200
Ser Leu Glu Leu Glu Cys Tyr Ser Val Ala Leu Ala Arg Gly Gly Leu
1205 1210 1215
Tyr Ile Leu Glu Ile Leu Glu Thr His Arg Ser Glu Arg Leu Tyr Ser
1220 1225 1230
Thr His Arg Leu Tyr Ser Ser Glu Arg Leu Glu Ala Ser Pro Leu Tyr
1235 1240 1245
Ser Gly Leu Tyr Thr Tyr Arg Ala Ser Asn Leu Tyr Ser Ala Leu Ala
1250 1255 1260
Leu Glu Ala Ser Asn Ala Ser Pro Leu Glu Cys Tyr Ser Ile Leu Glu
1265 1270 1275 1280
Leu Tyr Ser Val Ala Leu Ala Ser Asn Ala Ser Asn Thr Arg Pro Ala
1285 1290 1295
Ser Pro Leu Glu Pro His Glu Pro His Glu Ser Glu Arg Pro Arg Ser
1300 1305 1310
Glu Arg Gly Leu Ala Ser Pro Ala Ser Asn Pro His Glu Thr His Arg
1315 1320 1325
Ala Ser Asn Ala Ser Pro Leu Glu Ala Ser Asn Leu Tyr Ser Gly Leu
1330 1335 1340
Tyr Gly Leu Gly Leu Ile Leu Glu Thr His Arg Ser Glu Arg Ala Ser
1345 1350 1355 1360
Pro Thr His Arg Ala Ser Asn Ile Leu Glu Gly Leu Ala Leu Ala Ala
1365 1370 1375
Leu Ala Gly Leu Gly Leu Ala Ser Asn Ile Leu Glu Ser Glu Arg Leu
1380 1385 1390
Glu Ala Ser Pro Leu Glu Ile Leu Glu Gly Leu Asn Gly Leu Asn Thr
1395 1400 1405
Tyr Arg Thr Tyr Arg Leu Glu Thr His Arg Pro His Glu Ala Ser Asn
1410 1415 1420
Pro His Glu Ala Ser Pro Ala Ser Asn Gly Leu Pro Arg Gly Leu Ala
1425 1430 1435 1440
Ser Asn Ile Leu Glu Ser Glu Arg Ile Leu Glu Gly Leu Ala Ser Asn
1445 1450 1455
Leu Glu Ser Glu Arg Ser Glu Arg Ala Ser Pro Ile Leu Glu Ile Leu
1460 1465 1470
Glu Gly Leu Tyr Gly Leu Asn Leu Glu Gly Leu Leu Glu Met Glu Thr
1475 1480 1485
Pro Arg Ala Ser Asn Ile Leu Glu Gly Leu Ala Arg Gly Pro His Glu
1490 1495 1500
Pro Arg Ala Ser Asn Gly Leu Tyr Leu Tyr Ser Leu Tyr Ser Thr Tyr
1505 1510 1515 1520
Arg Gly Leu Leu Glu Ala Ser Pro Leu Tyr Ser Thr Tyr Arg Thr His
1525 1530 1535
Arg Met Glu Thr Pro His Glu His Ile Ser Thr Tyr Arg Leu Glu Ala
1540 1545 1550
Arg Gly Ala Leu Ala Gly Leu Asn Gly Leu Pro His Glu Gly Leu His
1555 1560 1565
Ile Ser Gly Leu Tyr Leu Tyr Ser Ser Glu Arg Ala Arg Gly Ile Leu
1570 1575 1580
Glu Ala Leu Ala Leu Glu Thr His Arg Ala Ser Asn Ser Glu Arg Val
1585 1590 1595 1600
Ala Leu Ala Ser Asn Gly Leu Ala Leu Ala Leu Glu Leu Glu Ala Ser
1605 1610 1615
Asn Pro Arg Ser Glu Arg Ala Arg Gly Val Ala Leu Thr Tyr Arg Thr
1620 1625 1630
His Arg Pro His Glu Pro His Glu Ser Glu Arg Ser Glu Arg Ala Ser
1635 1640 1645
Pro Thr Tyr Arg Val Ala Leu Leu Tyr Ser Leu Tyr Ser Val Ala Leu
1650 1655 1660
Ala Ser Asn Leu Tyr Ser Ala Leu Ala Thr His Arg Gly Leu Ala Leu
1665 1670 1675 1680
Ala Ala Leu Ala Met Glu Thr Pro His Glu Leu Glu Gly Leu Tyr Thr
1685 1690 1695
Arg Pro Val Ala Leu Gly Leu Gly Leu Asn Leu Glu Val Ala Leu Thr
1700 1705 1710
Tyr Arg Ala Ser Pro Pro His Glu Thr His Arg Ala Ser Pro Gly Leu
1715 1720 1725
Thr His Arg Ser Glu Arg Gly Leu Val Ala Leu Ser Glu Arg Thr His
1730 1735 1740
Arg Thr His Arg Ala Ser Pro Leu Tyr Ser Ile Leu Glu Ala Leu Ala
1745 1750 1755 1760
Ala Ser Pro Ile Leu Glu Thr His Arg Ile Leu Glu Ile Leu Glu Ile
1765 1770 1775
Leu Glu Pro Arg Thr Tyr Arg Ile Leu Glu Gly Leu Tyr Pro Arg Ala
1780 1785 1790
Leu Ala Leu Glu Ala Ser Asn Ile Leu Glu Gly Leu Tyr Ala Ser Asn
1795 1800 1805
Met Glu Thr Leu Glu Thr Tyr Arg Leu Tyr Ser Ala Ser Pro Ala Ser
1810 1815 1820
Pro Pro His Glu Val Ala Leu Gly Leu Tyr Ala Leu Ala Leu Glu Ile
1825 1830 1835 1840
Leu Glu Pro His Glu Ser Glu Arg Gly Leu Tyr Ala Leu Ala Val Ala
1845 1850 1855
Leu Ile Leu Glu Leu Glu Leu Glu Gly Leu Pro His Glu Ile Leu Glu
1860 1865 1870
Pro Arg Gly Leu Ile Leu Glu Ala Leu Ala Ile Leu Glu Pro Arg Val
1875 1880 1885
Ala Leu Leu Glu Gly Leu Tyr Thr His Arg Pro His Glu Ala Leu Ala
1890 1895 1900
Leu Glu Val Ala Leu Ser Glu Arg Thr Tyr Arg Ile Leu Glu Ala Leu
1905 1910 1915 1920
Ala Ala Ser Asn Leu Tyr Ser Val Ala Leu Leu Glu Thr His Arg Val
1925 1930 1935
Ala Leu Gly Leu Asn Thr His Arg Ile Leu Glu Ala Ser Pro Ala Ser
1940 1945 1950
Asn Ala Leu Ala Leu Glu Ser Glu Arg Leu Tyr Ser Ala Arg Gly Ala
1955 1960 1965
Ser Asn Gly Leu Leu Tyr Ser Thr Arg Pro Ala Ser Pro Gly Leu Val
1970 1975 1980
Ala Leu Thr Tyr Arg Leu Tyr Ser Thr Tyr Arg Ile Leu Glu Val Ala
1985 1990 1995 2000
Leu Thr His Arg Ala Ser Asn Thr Arg Pro Leu Glu Ala Leu Ala Leu
2005 2010 2015
Tyr Ser Val Ala Leu Ala Ser Asn Thr His Arg Gly Leu Asn Ile Leu
2020 2025 2030
Glu Ala Ser Pro Leu Glu Ile Leu Glu Ala Arg Gly Leu Tyr Ser Leu
2035 2040 2045
Tyr Ser Met Glu Thr Leu Tyr Ser Gly Leu Ala Leu Ala Leu Glu Gly
2050 2055 2060
Leu Ala Ser Asn Gly Leu Asn Ala Leu Ala Gly Leu Ala Leu Ala Thr
2065 2070 2075 2080
His Arg Leu Tyr Ser Ala Leu Ala Ile Leu Glu Ile Leu Glu Ala Ser
2085 2090 2095
Asn Thr Tyr Arg Gly Leu Asn Thr Tyr Arg Ala Ser Asn Gly Leu Asn
2100 2105 2110
Thr Tyr Arg Thr His Arg Gly Leu Gly Leu Gly Leu Leu Tyr Ser Ala
2115 2120 2125
Ser Asn Ala Ser Asn Ile Leu Glu Ala Ser Asn Pro His Glu Ala Ser
2130 2135 2140
Asn Ile Leu Glu Ala Ser Pro Ala Ser Pro Leu Glu Ser Glu Arg Ser
2145 2150 2155 2160
Glu Arg Leu Tyr Ser Leu Glu Ala Ser Asn Gly Leu Ser Glu Arg Ile
2165 2170 2175
Leu Glu Ala Ser Asn Leu Tyr Ser Ala Leu Ala Met Glu Thr Ile Leu
2180 2185 2190
Glu Ala Ser Asn Ile Leu Glu Ala Ser Asn Leu Tyr Ser Pro His Glu
2195 2200 2205
Leu Glu Ala Ser Asn Gly Leu Asn Cys Tyr Ser Ser Glu Arg Val Ala
2210 2215 2220
Leu Ser Glu Arg Thr Tyr Arg Leu Glu Met Glu Thr Ala Ser Asn Ser
2225 2230 2235 2240
Glu Arg Met Glu Thr Ile Leu Glu Pro Arg Thr Tyr Arg Gly Leu Tyr
2245 2250 2255
Val Ala Leu Leu Tyr Ser Ala Arg Gly Leu Glu Gly Leu Ala Ser Pro
2260 2265 2270
Pro His Glu Ala Ser Pro Ala Leu Ala Ser Glu Arg Leu Glu Leu Tyr
2275 2280 2285
Ser Ala Ser Pro Ala Leu Ala Leu Glu Leu Glu Leu Tyr Ser Thr Tyr
2290 2295 2300
Arg Ile Leu Glu Thr Tyr Arg Ala Ser Pro Ala Ser Asn Ala Arg Gly
2305 2310 2315 2320
Gly Leu Tyr Thr His Arg Leu Glu Ile Leu Glu Gly Leu Tyr Gly Leu
2325 2330 2335
Asn Val Ala Leu Ala Ser Pro Ala Arg Gly Leu Glu Leu Tyr Ser Ala
2340 2345 2350
Ser Pro Leu Tyr Ser Val Ala Leu Ala Ser Asn Ala Ser Asn Thr His
2355 2360 2365
Arg Leu Glu Ser Glu Arg Thr His Arg Ala Ser Pro Ile Leu Glu Pro
2370 2375 2380
Arg Pro His Glu Gly Leu Asn Leu Glu Ser Glu Arg Leu Tyr Ser Thr
2385 2390 2395 2400
Tyr Arg Val Ala Leu Ala Ser Pro Ala Ser Asn Gly Leu Asn Ala Arg
2405 2410 2415
Gly Leu Glu Leu Glu Ser Glu Arg Thr His Arg Pro His Glu Thr His
2420 2425 2430
Arg Gly Leu Thr Tyr Arg Ile Leu Glu Leu Tyr Ser Ala Ser Asn Ile
2435 2440 2445
Leu Glu Ile Leu Glu Ala Ser Asn Thr His Arg Ser Glu Arg Ile Leu
2450 2455 2460
Glu Leu Glu Ala Ser Asn Leu Glu Ala Arg Gly Thr Tyr Arg Gly Leu
2465 2470 2475 2480
Ser Glu Arg Ala Ser Asn His Ile Ser Leu Glu Ile Leu Glu Ala Ser
2485 2490 2495
Pro Leu Glu Ser Glu Arg Ala Arg Gly Thr Tyr Arg Ala Leu Ala Ser
2500 2505 2510
Glu Arg Leu Tyr Ser Ile Leu Glu Ala Ser Asn Ile Leu Glu Gly Leu
2515 2520 2525
Tyr Ser Glu Arg Leu Tyr Ser Val Ala Leu Ala Ser Asn Pro His Glu
2530 2535 2540
Ala Ser Pro Pro Arg Ile Leu Glu Ala Ser Pro Leu Tyr Ser Ala Ser
2545 2550 2555 2560
Asn Gly Leu Asn Ile Leu Glu Gly Leu Asn Leu Glu Pro His Glu Ala
2565 2570 2575
Ser Asn Leu Glu Gly Leu Ser Glu Arg Ser Glu Arg Leu Tyr Ser Ile
2580 2585 2590
Leu Glu Gly Leu Val Ala Leu Ile Leu Glu Leu Glu Leu Tyr Ser Ala
2595 2600 2605
Ser Asn Ala Leu Ala Ile Leu Glu Val Ala Leu Thr Tyr Arg Ala Ser
2610 2615 2620
Asn Ser Glu Arg Met Glu Thr Thr Tyr Arg Gly Leu Ala Ser Asn Pro
2625 2630 2635 2640
His Glu Ser Glu Arg Thr His Arg Ser Glu Arg Pro His Glu Thr Arg
2645 2650 2655
Pro Ile Leu Glu Ala Arg Gly Ile Leu Glu Pro Arg Leu Tyr Ser Thr
2660 2665 2670
Tyr Arg Pro His Glu Ala Ser Asn Ser Glu Arg Ile Leu Glu Ser Glu
2675 2680 2685
Arg Leu Glu Ala Ser Asn Ala Ser Asn Gly Leu Thr Tyr Arg Thr His
2690 2695 2700
Arg Ile Leu Glu Ile Leu Glu Ala Ser Asn Cys Tyr Ser Met Glu Thr
2705 2710 2715 2720
Gly Leu Ala Ser Asn Ala Ser Asn Ser Glu Arg Gly Leu Tyr Thr Arg
2725 2730 2735
Pro Leu Tyr Ser Val Ala Leu Ser Glu Arg Leu Glu Ala Ser Asn Thr
2740 2745 2750
Tyr Arg Gly Leu Tyr Gly Leu Ile Leu Glu Ile Leu Glu Thr Arg Pro
2755 2760 2765
Thr His Arg Leu Glu Gly Leu Asn Ala Ser Pro Thr His Arg Gly Leu
2770 2775 2780
Asn Gly Leu Ile Leu Glu Leu Tyr Ser Gly Leu Asn Ala Arg Gly Val
2785 2790 2795 2800
Ala Leu Val Ala Leu Pro His Glu Leu Tyr Ser Thr Tyr Arg Ser Glu
2805 2810 2815
Arg Gly Leu Asn Met Glu Thr Ile Leu Glu Ala Ser Asn Ile Leu Glu
2820 2825 2830
Ser Glu Arg Ala Ser Pro Thr Tyr Arg Ile Leu Glu Ala Ser Asn Ala
2835 2840 2845
Arg Gly Thr Arg Pro Ile Leu Glu Pro His Glu Val Ala Leu Thr His
2850 2855 2860
Arg Ile Leu Glu Thr His Arg Ala Ser Asn Ala Ser Asn Ala Arg Gly
2865 2870 2875 2880
Leu Glu Ala Ser Asn Ala Ser Asn Ser Glu Arg Leu Tyr Ser Ile Leu
2885 2890 2895
Glu Thr Tyr Arg Ile Leu Glu Ala Ser Asn Gly Leu Tyr Ala Arg Gly
2900 2905 2910
Leu Glu Ile Leu Glu Ala Ser Pro Gly Leu Asn Leu Tyr Ser Pro Arg
2915 2920 2925
Ile Leu Glu Ser Glu Arg Ala Ser Asn Leu Glu Gly Leu Tyr Ala Ser
2930 2935 2940
Asn Ile Leu Glu His Ile Ser Ala Leu Ala Ser Glu Arg Ala Ser Asn
2945 2950 2955 2960
Ala Ser Asn Ile Leu Glu Met Glu Thr Pro His Glu Leu Tyr Ser Leu
2965 2970 2975
Glu Ala Ser Pro Gly Leu Tyr Cys Tyr Ser Ala Arg Gly Ala Ser Pro
2980 2985 2990
Thr His Arg His Ile Ser Ala Arg Gly Thr Tyr Arg Ile Leu Glu Thr
2995 3000 3005
Arg Pro Ile Leu Glu Leu Tyr Ser Thr Tyr Arg Pro His Glu Ala Ser
3010 3015 3020
Asn Leu Glu Pro His Glu Ala Ser Pro Leu Tyr Ser Gly Leu Leu Glu
3025 3030 3035 3040
Ala Ser Asn Gly Leu Leu Tyr Ser Gly Leu Ile Leu Glu Leu Tyr Ser
3045 3050 3055
Ala Ser Pro Leu Glu Thr Tyr Arg Ala Ser Pro Ala Ser Asn Gly Leu
3060 3065 3070
Asn Ser Glu Arg Ala Ser Asn Ser Glu Arg Gly Leu Tyr Ile Leu Glu
3075 3080 3085
Leu Glu Leu Tyr Ser Ala Ser Pro Pro His Glu Thr Arg Pro Gly Leu
3090 3095 3100
Tyr Ala Ser Pro Thr Tyr Arg Leu Glu Gly Leu Asn Thr Tyr Arg Ala
3105 3110 3115 3120
Ser Pro Leu Tyr Ser Pro Arg Thr Tyr Arg Thr Tyr Arg Met Glu Thr
3125 3130 3135
Leu Glu Ala Ser Asn Leu Glu Thr Tyr Arg Ala Ser Pro Pro Arg Ala
3140 3145 3150
Ser Asn Leu Tyr Ser Thr Tyr Arg Val Ala Leu Ala Ser Pro Val Ala
3155 3160 3165
Leu Ala Ser Asn Ala Ser Asn Val Ala Leu Gly Leu Tyr Ile Leu Glu
3170 3175 3180
Ala Arg Gly Gly Leu Tyr Thr Tyr Arg Met Glu Thr Thr Tyr Arg Leu
3185 3190 3195 3200
Glu Leu Tyr Ser Gly Leu Tyr Pro Arg Ala Arg Gly Gly Leu Tyr Ser
3205 3210 3215
Glu Arg Val Ala Leu Met Glu Thr Thr His Arg Thr His Arg Ala Ser
3220 3225 3230
Asn Ile Leu Glu Thr Tyr Arg Leu Glu Ala Ser Asn Ser Glu Arg Ser
3235 3240 3245
Glu Arg Leu Glu Thr Tyr Arg Ala Arg Gly Gly Leu Tyr Thr His Arg
3250 3255 3260
Leu Tyr Ser Pro His Glu Ile Leu Glu Ile Leu Glu Leu Tyr Ser Leu
3265 3270 3275 3280
Tyr Ser Thr Tyr Arg Ala Leu Ala Ser Glu Arg Gly Leu Tyr Ala Ser
3285 3290 3295
Asn Leu Tyr Ser Ala Ser Pro Ala Ser Asn Ile Leu Glu Val Ala Leu
3300 3305 3310
Ala Arg Gly Ala Ser Asn Ala Ser Asn Ala Ser Pro Ala Arg Gly Val
3315 3320 3325
Ala Leu Thr Tyr Arg Ile Leu Glu Ala Ser Asn Val Ala Leu Val Ala
3330 3335 3340
Leu Val Ala Leu Leu Tyr Ser Ala Ser Asn Leu Tyr Ser Gly Leu Thr
3345 3350 3355 3360
Tyr Arg Ala Arg Gly Leu Glu Ala Leu Ala Thr His Arg Ala Ser Asn
3365 3370 3375
Ala Leu Ala Ser Glu Arg Gly Leu Asn Ala Leu Ala Gly Leu Tyr Val
3380 3385 3390
Ala Leu Gly Leu Leu Tyr Ser Ile Leu Glu Leu Glu Ser Glu Arg Ala
3395 3400 3405
Leu Ala Leu Glu Gly Leu Ile Leu Glu Pro Arg Ala Ser Pro Val Ala
3410 3415 3420
Leu Gly Leu Tyr Ala Ser Asn Leu Glu Ser Glu Arg Gly Leu Asn Val
3425 3430 3435 3440
Ala Leu Val Ala Leu Val Ala Leu Met Glu Thr Leu Tyr Ser Ser Glu
3445 3450 3455
Arg Leu Tyr Ser Ala Ser Asn Ala Ser Pro Gly Leu Asn Gly Leu Tyr
3460 3465 3470
Ile Leu Glu Thr His Arg Ala Ser Asn Leu Tyr Ser Cys Tyr Ser Leu
3475 3480 3485
Tyr Ser Met Glu Thr Ala Ser Asn Leu Glu Gly Leu Asn Ala Ser Pro
3490 3495 3500
Ala Ser Asn Ala Ser Asn Gly Leu Tyr Ala Ser Asn Ala Ser Pro Ile
3505 3510 3515 3520
Leu Glu Gly Leu Tyr Pro His Glu Ile Leu Glu Gly Leu Tyr Pro His
3525 3530 3535
Glu His Ile Ser Gly Leu Asn Pro His Glu Ala Ser Asn Ala Ser Asn
3540 3545 3550
Ile Leu Glu Ala Leu Ala Leu Tyr Ser Leu Glu Val Ala Leu Ala Leu
3555 3560 3565
Ala Ser Glu Arg Ala Ser Asn Thr Arg Pro Thr Tyr Arg Ala Ser Asn
3570 3575 3580
Ala Arg Gly Gly Leu Asn Ile Leu Glu Gly Leu Ala Arg Gly Ser Glu
3585 3590 3595 3600
Arg Ser Glu Arg Ala Arg Gly Thr His Arg Leu Glu Gly Leu Tyr Cys
3605 3610 3615
Tyr Ser Ser Glu Arg Thr Arg Pro Gly Leu Pro His Glu Ile Leu Glu
3620 3625 3630
Pro Arg Val Ala Leu Ala Ser Pro Ala Ser Pro Gly Leu Tyr Thr Arg
3635 3640 3645
Pro Gly Leu Tyr Gly Leu Ala Arg Gly Pro Arg Leu Glu
3650 3655 3660
<210> 3
<211> 3876
<212> DNA
<213> Clostridium botulinum
<400> 3
atgccagtta caataaataa ttttaattat aatgatccta ttgataataa taatattatt 60
atgatggagc ctccatttgc gagaggtacg gggagatatt ataaagcttt taaaatcaca 120
gatcgtattt ggataatacc ggaaagatat acttttggat ataaacctga ggattttaat 180
aaaagttccg gtatttttaa tagagatgtt tgtgaatatt atgatccaga ttacttaaat 240
actaatgata aaaagaatat atttttacaa acaatgatca agttatttaa tagaatcaaa 300
tcaaaaccat tgggtgaaaa gttattagag atgattataa atggtatacc ttatcttgga 360
gatagacgtg ttccactcga agagtttaac acaaacattg ctagtgtaac tgttaataaa 420
ttaatcagta atccaggaga agtggagcga aaaaaaggta ttttcgcaaa tttaataata 480
tttggacctg ggccagtttt aaatgaaaat gagactatag atataggtat acaaaatcat 540
tttgcatcaa gggaaggctt cgggggtata atgcaaatga agttttgccc agaatatgta 600
agcgtattta ataatgttca agaaaacaaa ggcgcaagta tatttaatag acgtggatat 660
ttttcagatc cagccttgat attaatgcat gaacttatac atgttttaca tggattatat 720
ggcattaaag tagatgattt accaattgta ccaaatgaaa aaaaattttt tatgcaatct 780
acagatgcta tacaggcaga agaactatat acatttggag gacaagatcc cagcatcata 840
actccttcta cggataaaag tatctatgat aaagttttgc aaaattttag agggatagtt 900
gatagactta acaaggtttt agtttgcata tcagatccta acattaatat taatatatat 960
aaaaataaat ttaaagataa atataaattc gttgaagatt ctgagggaaa atatagtata 1020
gatgtagaaa gttttgataa attatataaa agcttaatgt ttggttttac agaaactaat 1080
atagcagaaa attataaaat aaaaactaga gcttcttatt ttagtgattc cttaccacca 1140
gtaaaaataa aaaatttatt agataatgaa atctatacta tagaggaagg gtttaatata 1200
tctgataaag atatggaaaa agaatataga ggtcagaata aagctataaa taaacaagct 1260
tatgaagaaa ttagcaagga gcatttggct gtatataaga tacaaatgtg taaaagtgtt 1320
aaagctccag gaatatgtat tgatgttgat aatgaagatt tgttctttat agctgataaa 1380
aatagttttt cagatgattt atctaaaaac gaaagaatag aatataatac acagagtaat 1440
tatatagaaa atgacttccc tataaatgaa ttaattttag atactgattt aataagtaaa 1500
atagaattac caagtgaaaa tacagaatca cttactgatt ttaatgtaga tgttccagta 1560
tatgaaaaac aacccgctat aaaaaaaatt tttacagatg aaaataccat ctttcaatat 1620
ttatactctc agacatttcc tctagatata agagatataa gtttaacatc ttcatttgat 1680
gatgcattat tattttctaa caaagtttat tcattttttt ctatggatta tattaaaact 1740
gctaataaag tggtagaagc aggattattt gcaggttggg tgaaacagat agtaaatgat 1800
tttgtaatcg aagctaataa aagcaatact atggataaaa ttgcagatat atctctaatt 1860
gttccttata taggattagc tttaaatgta ggaaatgaaa cagctaaagg aaattttgaa 1920
aatgcttttg agattgcagg agccagtatt ctactagaat ttataccaga acttttaata 1980
cctgtagttg gagccttttt attagaatca tatattgaca ataaaaataa aattattaaa 2040
acaatagata atgctttaac taaaagaaat gaaaaatgga gtgatatgta cggattaata 2100
gtagcgcaat ggctctcaac agttaatact caattttata caataaaaga gggaatgtat 2160
aaggctttaa attatcaagc acaagcattg gaagaaataa taaaatacag atataatata 2220
tattctgaaa aagaaaagtc aaatattaac atcgatttta atgatataaa ttctaaactt 2280
aatgagggta ttaaccaagc tatagataat ataaataatt ttataaatgg atgttctgta 2340
tcatatttaa tgaaaaaaat gattccatta gctgtagaaa aattactaga ctttgataat 2400
actctcaaaa aaaatttgtt aaattatata gatgaaaata aattatattt gattggaagt 2460
gcagaatatg aaaaatcaaa agtaaataaa tacttgaaaa ccattatgcc gtttgatctt 2520
tcaatatata ccaatgatac aatactaata gaaatgttta ataaatataa tagcgaaatt 2580
ttaaataata ttatcttaaa tttaagatat aaggataata atttaataga tttatcagga 2640
tatggggcaa aggtagaggt atatgatgga gtcgagctta atgataaaaa tcaatttaaa 2700
ttaactagtt cagcaaatag taagattaga gtgactcaaa atcagaatat catatttaat 2760
agtgtgttcc ttgattttag cgttagcttt tggataagaa tacctaaata taagaatgat 2820
ggtatacaaa attatattca taatgaatat acaataatta attgtatgaa aaataattcg 2880
ggctggaaaa tatctattag gggtaatagg ataatatgga ctttaattga tataaatgga 2940
aaaaccaaat cggtattttt tgaatataac ataagagaag atatatcaga gtatataaat 3000
agatggtttt ttgtaactat tactaataat ttgaataacg ctaaaattta tattaatggt 3060
aagctagaat caaatacaga tattaaagat ataagagaag ttattgctaa tggtgaaata 3120
atatttaaat tagatggtga tatagataga acacaattta tttggatgaa atatttcagt 3180
atttttaata cggaattaag tcaatcaaat attgaagaaa gatataaaat tcaatcatat 3240
agcgaatatt taaaagattt ttggggaaat cctttaatgt acaataaaga atattatatg 3300
tttaatgcgg ggaataaaaa ttcatatatt aaactaaaga aagattcacc tgtaggtgaa 3360
attttaacac gtagcaaata taatcaaaat tctaaatata taaattatag agatttatat 3420
attggagaaa aatttattat aagaagaaag tcaaattctc aatctataaa tgatgatata 3480
gttagaaaag aagattatat atatctagat ttttttaatt taaatcaaga gtggagagta 3540
tatacctata aatattttaa gaaagaggaa gaaaaattgt ttttagctcc tataagtgat 3600
tctgatgagt tttacaatac tatacaaata aaagaatatg atgaacagcc aacatatagt 3660
tgtcagttgc tttttaaaaa agatgaagaa agtactgatg agataggatt gattggtatt 3720
catcgtttct acgaatctgg aattgtattt gaagagtata aagattattt ttgtataagt 3780
aaatggtact taaaagaggt aaaaaggaaa ccatataatt taaaattggg atgtaattgg 3840
cagtttattc ctaaagatga agggtggact gaataa 3876
<210> 4
<211> 3642
<212> PRT
<213> Clostridium botulinum
<400> 4
Met Glu Thr Pro Arg Val Ala Leu Thr His Arg Ile Leu Glu Ala Ser
1 5 10 15
Asn Ala Ser Asn Pro His Glu Ala Ser Asn Thr Tyr Arg Ala Ser Asn
20 25 30
Ala Ser Pro Pro Arg Ile Leu Glu Ala Ser Pro Ala Ser Asn Ala Ser
35 40 45
Asn Ala Ser Asn Ile Leu Glu Ile Leu Glu Met Glu Thr Met Glu Thr
50 55 60
Gly Leu Pro Arg Pro Arg Pro His Glu Ala Leu Ala Ala Arg Gly Gly
65 70 75 80
Leu Tyr Thr His Arg Gly Leu Tyr Ala Arg Gly Thr Tyr Arg Thr Tyr
85 90 95
Arg Leu Tyr Ser Ala Leu Ala Pro His Glu Leu Tyr Ser Ile Leu Glu
100 105 110
Thr His Arg Ala Ser Pro Ala Arg Gly Ile Leu Glu Thr Arg Pro Ile
115 120 125
Leu Glu Ile Leu Glu Pro Arg Gly Leu Ala Arg Gly Thr Tyr Arg Thr
130 135 140
His Arg Pro His Glu Gly Leu Tyr Thr Tyr Arg Leu Tyr Ser Pro Arg
145 150 155 160
Gly Leu Ala Ser Pro Pro His Glu Ala Ser Asn Leu Tyr Ser Ser Glu
165 170 175
Arg Ser Glu Arg Gly Leu Tyr Ile Leu Glu Pro His Glu Ala Ser Asn
180 185 190
Ala Arg Gly Ala Ser Pro Val Ala Leu Cys Tyr Ser Gly Leu Thr Tyr
195 200 205
Arg Thr Tyr Arg Ala Ser Pro Pro Arg Ala Ser Pro Thr Tyr Arg Leu
210 215 220
Glu Ala Ser Asn Thr His Arg Ala Ser Asn Ala Ser Pro Leu Tyr Ser
225 230 235 240
Leu Tyr Ser Ala Ser Asn Ile Leu Glu Pro His Glu Leu Glu Gly Leu
245 250 255
Asn Thr His Arg Met Glu Thr Ile Leu Glu Leu Tyr Ser Leu Glu Pro
260 265 270
His Glu Ala Ser Asn Ala Arg Gly Ile Leu Glu Leu Tyr Ser Ser Glu
275 280 285
Arg Leu Tyr Ser Pro Arg Leu Glu Gly Leu Tyr Gly Leu Leu Tyr Ser
290 295 300
Leu Glu Leu Glu Gly Leu Met Glu Thr Ile Leu Glu Ile Leu Glu Ala
305 310 315 320
Ser Asn Gly Leu Tyr Ile Leu Glu Pro Arg Thr Tyr Arg Leu Glu Gly
325 330 335
Leu Tyr Ala Ser Pro Ala Arg Gly Ala Arg Gly Val Ala Leu Pro Arg
340 345 350
Leu Glu Gly Leu Gly Leu Pro His Glu Ala Ser Asn Thr His Arg Ala
355 360 365
Ser Asn Ile Leu Glu Ala Leu Ala Ser Glu Arg Val Ala Leu Thr His
370 375 380
Arg Val Ala Leu Ala Ser Asn Leu Tyr Ser Leu Glu Ile Leu Glu Ser
385 390 395 400
Glu Arg Ala Ser Asn Pro Arg Gly Leu Tyr Gly Leu Val Ala Leu Gly
405 410 415
Leu Ala Arg Gly Leu Tyr Ser Leu Tyr Ser Gly Leu Tyr Ile Leu Glu
420 425 430
Pro His Glu Ala Leu Ala Ala Ser Asn Leu Glu Ile Leu Glu Ile Leu
435 440 445
Glu Pro His Glu Gly Leu Tyr Pro Arg Gly Leu Tyr Pro Arg Val Ala
450 455 460
Leu Leu Glu Ala Ser Asn Gly Leu Ala Ser Asn Gly Leu Thr His Arg
465 470 475 480
Ile Leu Glu Ala Ser Pro Ile Leu Glu Gly Leu Tyr Ile Leu Glu Gly
485 490 495
Leu Asn Ala Ser Asn His Ile Ser Pro His Glu Ala Leu Ala Ser Glu
500 505 510
Arg Ala Arg Gly Gly Leu Gly Leu Tyr Pro His Glu Gly Leu Tyr Gly
515 520 525
Leu Tyr Ile Leu Glu Met Glu Thr Gly Leu Asn Met Glu Thr Leu Tyr
530 535 540
Ser Pro His Glu Cys Tyr Ser Pro Arg Gly Leu Thr Tyr Arg Val Ala
545 550 555 560
Leu Ser Glu Arg Val Ala Leu Pro His Glu Ala Ser Asn Ala Ser Asn
565 570 575
Val Ala Leu Gly Leu Asn Gly Leu Ala Ser Asn Leu Tyr Ser Gly Leu
580 585 590
Tyr Ala Leu Ala Ser Glu Arg Ile Leu Glu Pro His Glu Ala Ser Asn
595 600 605
Ala Arg Gly Ala Arg Gly Gly Leu Tyr Thr Tyr Arg Pro His Glu Ser
610 615 620
Glu Arg Ala Ser Pro Pro Arg Ala Leu Ala Leu Glu Ile Leu Glu Leu
625 630 635 640
Glu Met Glu Thr His Ile Ser Gly Leu Leu Glu Ile Leu Glu His Ile
645 650 655
Ser Val Ala Leu Leu Glu His Ile Ser Gly Leu Tyr Leu Glu Thr Tyr
660 665 670
Arg Gly Leu Tyr Ile Leu Glu Leu Tyr Ser Val Ala Leu Ala Ser Pro
675 680 685
Ala Ser Pro Leu Glu Pro Arg Ile Leu Glu Val Ala Leu Pro Arg Ala
690 695 700
Ser Asn Gly Leu Leu Tyr Ser Leu Tyr Ser Pro His Glu Pro His Glu
705 710 715 720
Met Glu Thr Gly Leu Asn Ser Glu Arg Thr His Arg Ala Ser Pro Ala
725 730 735
Leu Ala Ile Leu Glu Gly Leu Asn Ala Leu Ala Gly Leu Gly Leu Leu
740 745 750
Glu Thr Tyr Arg Thr His Arg Pro His Glu Gly Leu Tyr Gly Leu Tyr
755 760 765
Gly Leu Asn Ala Ser Pro Pro Arg Ser Glu Arg Ile Leu Glu Ile Leu
770 775 780
Glu Thr His Arg Pro Arg Ser Glu Arg Thr His Arg Ala Ser Pro Leu
785 790 795 800
Tyr Ser Ser Glu Arg Ile Leu Glu Thr Tyr Arg Ala Ser Pro Leu Tyr
805 810 815
Ser Val Ala Leu Leu Glu Gly Leu Asn Ala Ser Asn Pro His Glu Ala
820 825 830
Arg Gly Gly Leu Tyr Ile Leu Glu Val Ala Leu Ala Ser Pro Ala Arg
835 840 845
Gly Leu Glu Ala Ser Asn Leu Tyr Ser Val Ala Leu Leu Glu Val Ala
850 855 860
Leu Cys Tyr Ser Ile Leu Glu Ser Glu Arg Ala Ser Pro Pro Arg Ala
865 870 875 880
Ser Asn Ile Leu Glu Ala Ser Asn Ile Leu Glu Ala Ser Asn Ile Leu
885 890 895
Glu Thr Tyr Arg Leu Tyr Ser Ala Ser Asn Leu Tyr Ser Pro His Glu
900 905 910
Leu Tyr Ser Ala Ser Pro Leu Tyr Ser Thr Tyr Arg Leu Tyr Ser Pro
915 920 925
His Glu Val Ala Leu Gly Leu Ala Ser Pro Ser Glu Arg Gly Leu Gly
930 935 940
Leu Tyr Leu Tyr Ser Thr Tyr Arg Ser Glu Arg Ile Leu Glu Ala Ser
945 950 955 960
Pro Val Ala Leu Gly Leu Ser Glu Arg Pro His Glu Ala Ser Pro Leu
965 970 975
Tyr Ser Leu Glu Thr Tyr Arg Leu Tyr Ser Ser Glu Arg Leu Glu Met
980 985 990
Glu Thr Pro His Glu Gly Leu Tyr Pro His Glu Thr His Arg Gly Leu
995 1000 1005
Thr His Arg Ala Ser Asn Ile Leu Glu Ala Leu Ala Gly Leu Ala Ser
1010 1015 1020
Asn Thr Tyr Arg Leu Tyr Ser Ile Leu Glu Leu Tyr Ser Thr His Arg
1025 1030 1035 1040
Ala Arg Gly Ala Leu Ala Ser Glu Arg Thr Tyr Arg Pro His Glu Ser
1045 1050 1055
Glu Arg Ala Ser Pro Ser Glu Arg Leu Glu Pro Arg Pro Arg Val Ala
1060 1065 1070
Leu Leu Tyr Ser Ile Leu Glu Leu Tyr Ser Ala Ser Asn Leu Glu Leu
1075 1080 1085
Glu Ala Ser Pro Ala Ser Asn Gly Leu Ile Leu Glu Thr Tyr Arg Thr
1090 1095 1100
His Arg Ile Leu Glu Gly Leu Gly Leu Gly Leu Tyr Pro His Glu Ala
1105 1110 1115 1120
Ser Asn Ile Leu Glu Ser Glu Arg Ala Ser Pro Leu Tyr Ser Ala Ser
1125 1130 1135
Pro Met Glu Thr Gly Leu Leu Tyr Ser Gly Leu Thr Tyr Arg Ala Arg
1140 1145 1150
Gly Gly Leu Tyr Gly Leu Asn Ala Ser Asn Leu Tyr Ser Ala Leu Ala
1155 1160 1165
Ile Leu Glu Ala Ser Asn Leu Tyr Ser Gly Leu Asn Ala Leu Ala Thr
1170 1175 1180
Tyr Arg Gly Leu Gly Leu Ile Leu Glu Ser Glu Arg Leu Tyr Ser Gly
1185 1190 1195 1200
Leu His Ile Ser Leu Glu Ala Leu Ala Val Ala Leu Thr Tyr Arg Leu
1205 1210 1215
Tyr Ser Ile Leu Glu Gly Leu Asn Met Glu Thr Cys Tyr Ser Leu Tyr
1220 1225 1230
Ser Ser Glu Arg Val Ala Leu Leu Tyr Ser Ala Leu Ala Pro Arg Gly
1235 1240 1245
Leu Tyr Ile Leu Glu Cys Tyr Ser Ile Leu Glu Ala Ser Pro Val Ala
1250 1255 1260
Leu Ala Ser Pro Ala Ser Asn Gly Leu Ala Ser Pro Leu Glu Pro His
1265 1270 1275 1280
Glu Pro His Glu Ile Leu Glu Ala Leu Ala Ala Ser Pro Leu Tyr Ser
1285 1290 1295
Ala Ser Asn Ser Glu Arg Pro His Glu Ser Glu Arg Ala Ser Pro Ala
1300 1305 1310
Ser Pro Leu Glu Ser Glu Arg Leu Tyr Ser Ala Ser Asn Gly Leu Ala
1315 1320 1325
Arg Gly Ile Leu Glu Gly Leu Thr Tyr Arg Ala Ser Asn Thr His Arg
1330 1335 1340
Gly Leu Asn Ser Glu Arg Ala Ser Asn Thr Tyr Arg Ile Leu Glu Gly
1345 1350 1355 1360
Leu Ala Ser Asn Ala Ser Pro Pro His Glu Pro Arg Ile Leu Glu Ala
1365 1370 1375
Ser Asn Gly Leu Leu Glu Ile Leu Glu Leu Glu Ala Ser Pro Thr His
1380 1385 1390
Arg Ala Ser Pro Leu Glu Ile Leu Glu Ser Glu Arg Leu Tyr Ser Ile
1395 1400 1405
Leu Glu Gly Leu Leu Glu Pro Arg Ser Glu Arg Gly Leu Ala Ser Asn
1410 1415 1420
Thr His Arg Gly Leu Ser Glu Arg Leu Glu Thr His Arg Ala Ser Pro
1425 1430 1435 1440
Pro His Glu Ala Ser Asn Val Ala Leu Ala Ser Pro Val Ala Leu Pro
1445 1450 1455
Arg Val Ala Leu Thr Tyr Arg Gly Leu Leu Tyr Ser Gly Leu Asn Pro
1460 1465 1470
Arg Ala Leu Ala Ile Leu Glu Leu Tyr Ser Leu Tyr Ser Ile Leu Glu
1475 1480 1485
Pro His Glu Thr His Arg Ala Ser Pro Gly Leu Ala Ser Asn Thr His
1490 1495 1500
Arg Ile Leu Glu Pro His Glu Gly Leu Asn Thr Tyr Arg Leu Glu Thr
1505 1510 1515 1520
Tyr Arg Ser Glu Arg Gly Leu Asn Thr His Arg Pro His Glu Pro Arg
1525 1530 1535
Leu Glu Ala Ser Pro Ile Leu Glu Ala Arg Gly Ala Ser Pro Ile Leu
1540 1545 1550
Glu Ser Glu Arg Leu Glu Thr His Arg Ser Glu Arg Ser Glu Arg Pro
1555 1560 1565
His Glu Ala Ser Pro Ala Ser Pro Ala Leu Ala Leu Glu Leu Glu Pro
1570 1575 1580
His Glu Ser Glu Arg Ala Ser Asn Leu Tyr Ser Val Ala Leu Thr Tyr
1585 1590 1595 1600
Arg Ser Glu Arg Pro His Glu Pro His Glu Ser Glu Arg Met Glu Thr
1605 1610 1615
Ala Ser Pro Thr Tyr Arg Ile Leu Glu Leu Tyr Ser Thr His Arg Ala
1620 1625 1630
Leu Ala Ala Ser Asn Leu Tyr Ser Val Ala Leu Val Ala Leu Gly Leu
1635 1640 1645
Ala Leu Ala Gly Leu Tyr Leu Glu Pro His Glu Ala Leu Ala Gly Leu
1650 1655 1660
Tyr Thr Arg Pro Val Ala Leu Leu Tyr Ser Gly Leu Asn Ile Leu Glu
1665 1670 1675 1680
Val Ala Leu Ala Ser Asn Ala Ser Pro Pro His Glu Val Ala Leu Ile
1685 1690 1695
Leu Glu Gly Leu Ala Leu Ala Ala Ser Asn Leu Tyr Ser Ser Glu Arg
1700 1705 1710
Ala Ser Asn Thr His Arg Met Glu Thr Ala Ser Pro Leu Tyr Ser Ile
1715 1720 1725
Leu Glu Ala Leu Ala Ala Ser Pro Ile Leu Glu Ser Glu Arg Leu Glu
1730 1735 1740
Ile Leu Glu Val Ala Leu Pro Arg Thr Tyr Arg Ile Leu Glu Gly Leu
1745 1750 1755 1760
Tyr Leu Glu Ala Leu Ala Leu Glu Ala Ser Asn Val Ala Leu Gly Leu
1765 1770 1775
Tyr Ala Ser Asn Gly Leu Thr His Arg Ala Leu Ala Leu Tyr Ser Gly
1780 1785 1790
Leu Tyr Ala Ser Asn Pro His Glu Gly Leu Ala Ser Asn Ala Leu Ala
1795 1800 1805
Pro His Glu Gly Leu Ile Leu Glu Ala Leu Ala Gly Leu Tyr Ala Leu
1810 1815 1820
Ala Ser Glu Arg Ile Leu Glu Leu Glu Leu Glu Gly Leu Pro His Glu
1825 1830 1835 1840
Ile Leu Glu Pro Arg Gly Leu Leu Glu Leu Glu Ile Leu Glu Pro Arg
1845 1850 1855
Val Ala Leu Val Ala Leu Gly Leu Tyr Ala Leu Ala Pro His Glu Leu
1860 1865 1870
Glu Leu Glu Gly Leu Ser Glu Arg Thr Tyr Arg Ile Leu Glu Ala Ser
1875 1880 1885
Pro Ala Ser Asn Leu Tyr Ser Ala Ser Asn Leu Tyr Ser Ile Leu Glu
1890 1895 1900
Ile Leu Glu Leu Tyr Ser Thr His Arg Ile Leu Glu Ala Ser Pro Ala
1905 1910 1915 1920
Ser Asn Ala Leu Ala Leu Glu Thr His Arg Leu Tyr Ser Ala Arg Gly
1925 1930 1935
Ala Ser Asn Gly Leu Leu Tyr Ser Thr Arg Pro Ser Glu Arg Ala Ser
1940 1945 1950
Pro Met Glu Thr Thr Tyr Arg Gly Leu Tyr Leu Glu Ile Leu Glu Val
1955 1960 1965
Ala Leu Ala Leu Ala Gly Leu Asn Thr Arg Pro Leu Glu Ser Glu Arg
1970 1975 1980
Thr His Arg Val Ala Leu Ala Ser Asn Thr His Arg Gly Leu Asn Pro
1985 1990 1995 2000
His Glu Thr Tyr Arg Thr His Arg Ile Leu Glu Leu Tyr Ser Gly Leu
2005 2010 2015
Gly Leu Tyr Met Glu Thr Thr Tyr Arg Leu Tyr Ser Ala Leu Ala Leu
2020 2025 2030
Glu Ala Ser Asn Thr Tyr Arg Gly Leu Asn Ala Leu Ala Gly Leu Asn
2035 2040 2045
Ala Leu Ala Leu Glu Gly Leu Gly Leu Ile Leu Glu Ile Leu Glu Leu
2050 2055 2060
Tyr Ser Thr Tyr Arg Ala Arg Gly Thr Tyr Arg Ala Ser Asn Ile Leu
2065 2070 2075 2080
Glu Thr Tyr Arg Ser Glu Arg Gly Leu Leu Tyr Ser Gly Leu Leu Tyr
2085 2090 2095
Ser Ser Glu Arg Ala Ser Asn Ile Leu Glu Ala Ser Asn Ile Leu Glu
2100 2105 2110
Ala Ser Pro Pro His Glu Ala Ser Asn Ala Ser Pro Ile Leu Glu Ala
2115 2120 2125
Ser Asn Ser Glu Arg Leu Tyr Ser Leu Glu Ala Ser Asn Gly Leu Gly
2130 2135 2140
Leu Tyr Ile Leu Glu Ala Ser Asn Gly Leu Asn Ala Leu Ala Ile Leu
2145 2150 2155 2160
Glu Ala Ser Pro Ala Ser Asn Ile Leu Glu Ala Ser Asn Ala Ser Asn
2165 2170 2175
Pro His Glu Ile Leu Glu Ala Ser Asn Gly Leu Tyr Cys Tyr Ser Ser
2180 2185 2190
Glu Arg Val Ala Leu Ser Glu Arg Thr Tyr Arg Leu Glu Met Glu Thr
2195 2200 2205
Leu Tyr Ser Leu Tyr Ser Met Glu Thr Ile Leu Glu Pro Arg Leu Glu
2210 2215 2220
Ala Leu Ala Val Ala Leu Gly Leu Leu Tyr Ser Leu Glu Leu Glu Ala
2225 2230 2235 2240
Ser Pro Pro His Glu Ala Ser Pro Ala Ser Asn Thr His Arg Leu Glu
2245 2250 2255
Leu Tyr Ser Leu Tyr Ser Ala Ser Asn Leu Glu Leu Glu Ala Ser Asn
2260 2265 2270
Thr Tyr Arg Ile Leu Glu Ala Ser Pro Gly Leu Ala Ser Asn Leu Tyr
2275 2280 2285
Ser Leu Glu Thr Tyr Arg Leu Glu Ile Leu Glu Gly Leu Tyr Ser Glu
2290 2295 2300
Arg Ala Leu Ala Gly Leu Thr Tyr Arg Gly Leu Leu Tyr Ser Ser Glu
2305 2310 2315 2320
Arg Leu Tyr Ser Val Ala Leu Ala Ser Asn Leu Tyr Ser Thr Tyr Arg
2325 2330 2335
Leu Glu Leu Tyr Ser Thr His Arg Ile Leu Glu Met Glu Thr Pro Arg
2340 2345 2350
Pro His Glu Ala Ser Pro Leu Glu Ser Glu Arg Ile Leu Glu Thr Tyr
2355 2360 2365
Arg Thr His Arg Ala Ser Asn Ala Ser Pro Thr His Arg Ile Leu Glu
2370 2375 2380
Leu Glu Ile Leu Glu Gly Leu Met Glu Thr Pro His Glu Ala Ser Asn
2385 2390 2395 2400
Leu Tyr Ser Thr Tyr Arg Ala Ser Asn Ser Glu Arg Gly Leu Ile Leu
2405 2410 2415
Glu Leu Glu Ala Ser Asn Ala Ser Asn Ile Leu Glu Ile Leu Glu Leu
2420 2425 2430
Glu Ala Ser Asn Leu Glu Ala Arg Gly Thr Tyr Arg Leu Tyr Ser Ala
2435 2440 2445
Ser Pro Ala Ser Asn Ala Ser Asn Leu Glu Ile Leu Glu Ala Ser Pro
2450 2455 2460
Leu Glu Ser Glu Arg Gly Leu Tyr Thr Tyr Arg Gly Leu Tyr Ala Leu
2465 2470 2475 2480
Ala Leu Tyr Ser Val Ala Leu Gly Leu Val Ala Leu Thr Tyr Arg Ala
2485 2490 2495
Ser Pro Gly Leu Tyr Val Ala Leu Gly Leu Leu Glu Ala Ser Asn Ala
2500 2505 2510
Ser Pro Leu Tyr Ser Ala Ser Asn Gly Leu Asn Pro His Glu Leu Tyr
2515 2520 2525
Ser Leu Glu Thr His Arg Ser Glu Arg Ser Glu Arg Ala Leu Ala Ala
2530 2535 2540
Ser Asn Ser Glu Arg Leu Tyr Ser Ile Leu Glu Ala Arg Gly Val Ala
2545 2550 2555 2560
Leu Thr His Arg Gly Leu Asn Ala Ser Asn Gly Leu Asn Ala Ser Asn
2565 2570 2575
Ile Leu Glu Ile Leu Glu Pro His Glu Ala Ser Asn Ser Glu Arg Val
2580 2585 2590
Ala Leu Pro His Glu Leu Glu Ala Ser Pro Pro His Glu Ser Glu Arg
2595 2600 2605
Val Ala Leu Ser Glu Arg Pro His Glu Thr Arg Pro Ile Leu Glu Ala
2610 2615 2620
Arg Gly Ile Leu Glu Pro Arg Leu Tyr Ser Thr Tyr Arg Leu Tyr Ser
2625 2630 2635 2640
Ala Ser Asn Ala Ser Pro Gly Leu Tyr Ile Leu Glu Gly Leu Asn Ala
2645 2650 2655
Ser Asn Thr Tyr Arg Ile Leu Glu His Ile Ser Ala Ser Asn Gly Leu
2660 2665 2670
Thr Tyr Arg Thr His Arg Ile Leu Glu Ile Leu Glu Ala Ser Asn Cys
2675 2680 2685
Tyr Ser Met Glu Thr Leu Tyr Ser Ala Ser Asn Ala Ser Asn Ser Glu
2690 2695 2700
Arg Gly Leu Tyr Thr Arg Pro Leu Tyr Ser Ile Leu Glu Ser Glu Arg
2705 2710 2715 2720
Ile Leu Glu Ala Arg Gly Gly Leu Tyr Ala Ser Asn Ala Arg Gly Ile
2725 2730 2735
Leu Glu Ile Leu Glu Thr Arg Pro Thr His Arg Leu Glu Ile Leu Glu
2740 2745 2750
Ala Ser Pro Ile Leu Glu Ala Ser Asn Gly Leu Tyr Leu Tyr Ser Thr
2755 2760 2765
His Arg Leu Tyr Ser Ser Glu Arg Val Ala Leu Pro His Glu Pro His
2770 2775 2780
Glu Gly Leu Thr Tyr Arg Ala Ser Asn Ile Leu Glu Ala Arg Gly Gly
2785 2790 2795 2800
Leu Ala Ser Pro Ile Leu Glu Ser Glu Arg Gly Leu Thr Tyr Arg Ile
2805 2810 2815
Leu Glu Ala Ser Asn Ala Arg Gly Thr Arg Pro Pro His Glu Pro His
2820 2825 2830
Glu Val Ala Leu Thr His Arg Ile Leu Glu Thr His Arg Ala Ser Asn
2835 2840 2845
Ala Ser Asn Leu Glu Ala Ser Asn Ala Ser Asn Ala Leu Ala Leu Tyr
2850 2855 2860
Ser Ile Leu Glu Thr Tyr Arg Ile Leu Glu Ala Ser Asn Gly Leu Tyr
2865 2870 2875 2880
Leu Tyr Ser Leu Glu Gly Leu Ser Glu Arg Ala Ser Asn Thr His Arg
2885 2890 2895
Ala Ser Pro Ile Leu Glu Leu Tyr Ser Ala Ser Pro Ile Leu Glu Ala
2900 2905 2910
Arg Gly Gly Leu Val Ala Leu Ile Leu Glu Ala Leu Ala Ala Ser Asn
2915 2920 2925
Gly Leu Tyr Gly Leu Ile Leu Glu Ile Leu Glu Pro His Glu Leu Tyr
2930 2935 2940
Ser Leu Glu Ala Ser Pro Gly Leu Tyr Ala Ser Pro Ile Leu Glu Ala
2945 2950 2955 2960
Ser Pro Ala Arg Gly Thr His Arg Gly Leu Asn Pro His Glu Ile Leu
2965 2970 2975
Glu Thr Arg Pro Met Glu Thr Leu Tyr Ser Thr Tyr Arg Pro His Glu
2980 2985 2990
Ser Glu Arg Ile Leu Glu Pro His Glu Ala Ser Asn Thr His Arg Gly
2995 3000 3005
Leu Leu Glu Ser Glu Arg Gly Leu Asn Ser Glu Arg Ala Ser Asn Ile
3010 3015 3020
Leu Glu Gly Leu Gly Leu Ala Arg Gly Thr Tyr Arg Leu Tyr Ser Ile
3025 3030 3035 3040
Leu Glu Gly Leu Asn Ser Glu Arg Thr Tyr Arg Ser Glu Arg Gly Leu
3045 3050 3055
Thr Tyr Arg Leu Glu Leu Tyr Ser Ala Ser Pro Pro His Glu Thr Arg
3060 3065 3070
Pro Gly Leu Tyr Ala Ser Asn Pro Arg Leu Glu Met Glu Thr Thr Tyr
3075 3080 3085
Arg Ala Ser Asn Leu Tyr Ser Gly Leu Thr Tyr Arg Thr Tyr Arg Met
3090 3095 3100
Glu Thr Pro His Glu Ala Ser Asn Ala Leu Ala Gly Leu Tyr Ala Ser
3105 3110 3115 3120
Asn Leu Tyr Ser Ala Ser Asn Ser Glu Arg Thr Tyr Arg Ile Leu Glu
3125 3130 3135
Leu Tyr Ser Leu Glu Leu Tyr Ser Leu Tyr Ser Ala Ser Pro Ser Glu
3140 3145 3150
Arg Pro Arg Val Ala Leu Gly Leu Tyr Gly Leu Ile Leu Glu Leu Glu
3155 3160 3165
Thr His Arg Ala Arg Gly Ser Glu Arg Leu Tyr Ser Thr Tyr Arg Ala
3170 3175 3180
Ser Asn Gly Leu Asn Ala Ser Asn Ser Glu Arg Leu Tyr Ser Thr Tyr
3185 3190 3195 3200
Arg Ile Leu Glu Ala Ser Asn Thr Tyr Arg Ala Arg Gly Ala Ser Pro
3205 3210 3215
Leu Glu Thr Tyr Arg Ile Leu Glu Gly Leu Tyr Gly Leu Leu Tyr Ser
3220 3225 3230
Pro His Glu Ile Leu Glu Ile Leu Glu Ala Arg Gly Ala Arg Gly Leu
3235 3240 3245
Tyr Ser Ser Glu Arg Ala Ser Asn Ser Glu Arg Gly Leu Asn Ser Glu
3250 3255 3260
Arg Ile Leu Glu Ala Ser Asn Ala Ser Pro Ala Ser Pro Ile Leu Glu
3265 3270 3275 3280
Val Ala Leu Ala Arg Gly Leu Tyr Ser Gly Leu Ala Ser Pro Thr Tyr
3285 3290 3295
Arg Ile Leu Glu Thr Tyr Arg Leu Glu Ala Ser Pro Pro His Glu Pro
3300 3305 3310
His Glu Ala Ser Asn Leu Glu Ala Ser Asn Gly Leu Asn Gly Leu Thr
3315 3320 3325
Arg Pro Ala Arg Gly Val Ala Leu Thr Tyr Arg Thr His Arg Thr Tyr
3330 3335 3340
Arg Leu Tyr Ser Thr Tyr Arg Pro His Glu Leu Tyr Ser Leu Tyr Ser
3345 3350 3355 3360
Gly Leu Gly Leu Gly Leu Leu Tyr Ser Leu Glu Pro His Glu Leu Glu
3365 3370 3375
Ala Leu Ala Pro Arg Ile Leu Glu Ser Glu Arg Ala Ser Pro Ser Glu
3380 3385 3390
Arg Ala Ser Pro Gly Leu Pro His Glu Thr Tyr Arg Ala Ser Asn Thr
3395 3400 3405
His Arg Ile Leu Glu Gly Leu Asn Ile Leu Glu Leu Tyr Ser Gly Leu
3410 3415 3420
Thr Tyr Arg Ala Ser Pro Gly Leu Gly Leu Asn Pro Arg Thr His Arg
3425 3430 3435 3440
Thr Tyr Arg Ser Glu Arg Cys Tyr Ser Gly Leu Asn Leu Glu Leu Glu
3445 3450 3455
Pro His Glu Leu Tyr Ser Leu Tyr Ser Ala Ser Pro Gly Leu Gly Leu
3460 3465 3470
Ser Glu Arg Thr His Arg Ala Ser Pro Gly Leu Ile Leu Glu Gly Leu
3475 3480 3485
Tyr Leu Glu Ile Leu Glu Gly Leu Tyr Ile Leu Glu His Ile Ser Ala
3490 3495 3500
Arg Gly Pro His Glu Thr Tyr Arg Gly Leu Ser Glu Arg Gly Leu Tyr
3505 3510 3515 3520
Ile Leu Glu Val Ala Leu Pro His Glu Gly Leu Gly Leu Thr Tyr Arg
3525 3530 3535
Leu Tyr Ser Ala Ser Pro Thr Tyr Arg Pro His Glu Cys Tyr Ser Ile
3540 3545 3550
Leu Glu Ser Glu Arg Leu Tyr Ser Thr Arg Pro Thr Tyr Arg Leu Glu
3555 3560 3565
Leu Tyr Ser Gly Leu Val Ala Leu Leu Tyr Ser Ala Arg Gly Leu Tyr
3570 3575 3580
Ser Pro Arg Thr Tyr Arg Ala Ser Asn Leu Glu Leu Tyr Ser Leu Glu
3585 3590 3595 3600
Gly Leu Tyr Cys Tyr Ser Ala Ser Asn Thr Arg Pro Gly Leu Asn Pro
3605 3610 3615
His Glu Ile Leu Glu Pro Arg Leu Tyr Ser Ala Ser Pro Gly Leu Gly
3620 3625 3630
Leu Tyr Thr Arg Pro Thr His Arg Gly Leu
3635 3640
<210> 5
<211> 3843
<212> DNA
<213> Clostridium botulinum
<400> 5
atgccaataa caattaacaa ctttaattat tcagatcctg ttgataataa aaatatttta 60
tatttagata ctcatttaaa tacattagct aatgagcctg aaaaagcctt tcgcattata 120
gggaatatat gggtaatacc cgatagattt tcaagagatt ctaatccaaa tttaaataaa 180
cctcctcgag ttacaagccc taaaagtggt tattatgatc ctaattattt gagtactgat 240
tctgaaaaag atacattttt aaaagaaatt ataaagttat ttaaaagaat taactctaga 300
gaaataggag aagaattaat atatagactt gcaacagaca taccctttcc tgggaataac 360
aatactccaa ttaatacttt tgattttgat gtagatttta acagtgttga tgttaaaact 420
agacaaggta acaactgggt taaaactggt agtataaatc ctagtgttat aataactgga 480
cctagagaaa acattataga cccagaaact tctacgttta aattaactaa caatactttt 540
gcggcacaag aaggatttgg tgctttatca ataatttcaa tatcacctag atttatgcta 600
acatatagta atgcaactaa taatgtagga gagggtagat tttctaagtc tgaattttgc 660
atggatccaa tactaatttt aatgcatgaa cttaatcatg caatgcataa tttatatgga 720
atagctatac caaatgatca aagaatttca tctgtaacta gtaatatttt ttattctcaa 780
tataaggtga aattagagta tgcagaaata tatgcatttg gaggtccaac tatagacctt 840
attcctaaaa gtgcaaggaa atattttgag gaaaaggcat tggattatta tagatccata 900
gctaaaagac ttaatagtat aactactgca aatccttcaa gctttaataa atatatagga 960
gaatataaac agaaacttat tagaaagtat agattcgtag tagaatcttc aggtgaagtt 1020
gcagtagatc gtaataagtt tgctgagtta tataaagaac ttacacaaat atttacagaa 1080
tttaactacg ctaaaatata taatgtacaa aataggaaaa tatatctttc aaatgtatat 1140
actccggtta cggcaaatat attagacgat aatgtttatg atatacaaaa tggatttaac 1200
atacctaaaa gtaatttaaa tgtactattt atgggtcaaa atttatctcg aaatccagca 1260
ttaagaaaag tcaatcctga aaatatgctt tatttattta caaaattttg ccataaagca 1320
atagatggta gatcattata taataaaaca ttagattgta gagagctttt agttaaaaat 1380
actgacttac cctttatagg tgatattagt gatatcaaaa ctgatatatt tttaagcaaa 1440
gatattaatg aagaaactga agttatagac tatccggaca atgtttcagt ggatcaagtt 1500
attctcagta agaatacctc agaacatgga caactagatt tattataccc tattattgaa 1560
ggtgagagtc aagtattacc gggagagaat caagtctttt atgataatag aactcaaaat 1620
gttgattatt tgaattctta ttattaccta gaatctcaaa aactaagtga taatgttgaa 1680
gattttactt ttacgacatc aattgaggaa gctttggata atagtggaaa agtatatact 1740
tactttccta aactagctga taaagtaaat acgggtgttc aaggtggttt atttttaatg 1800
tgggcaaatg atgtagttga agattttact acaaatattc taagaaaaga tacattagat 1860
aaaatatcag atgtatcagc tattattccc tatataggac ctgcattaaa tataagtaat 1920
tctgtaagaa ggggaaattt tactgaagca tttgcagtta ccggtgtaac tattttatta 1980
gaagcgtttc aagaatttac aatacctgca cttggtgcat ttgtgattta tagtaaggtt 2040
caagaaagaa acgagattat taaaactata gataattgtt tagaacaaag gattaaaaga 2100
tggaaagatt catatgaatg gatgatagga acgtggttat ccaggattac tactcaattt 2160
aataatataa gttatcaaat gtatgattct ttaaattatc aggcagatgc aatcaaagat 2220
aaaatagatt tagaatataa aaaatactca ggaagtgata aagaaaatat aaaaagtcaa 2280
gttgaaaatt taaaaaatag tttagatata aaaatctcgg aagcaatgaa taatataaat 2340
aaatttatac gagaatgttc tgtaacatac ttatttaaaa atatgctccc taaagtaatt 2400
gatgaattaa ataagtttga tttaaaaact aaaacagaat taattaatct tatagatagt 2460
cataatatta ttctagttgg tgaagtagat agattaaaag caaaagtaaa tgagagtttt 2520
gaaaatacaa taccctttaa tattttttca tatactaata attctttatt aaaagatata 2580
attaatgaat atttcaatag tattaatgat tcaaaaattt tgagcttaca aaacaaaaaa 2640
aatgctttag tggatacatc aggatataat gcagaagtga ggctagaagg tgatgttcaa 2700
gttaatacga tatatacaaa tgattttaaa ttaagtagtt caggagataa aattatagta 2760
aatttaaata ataatatttt atatagcgct atttatgaga actctagtgt tagtttttgg 2820
attaagatat ctaaagattt aactaattct cataatgaat atacaataat taatagtata 2880
aaacaaaatt ctgggtggaa attatgtatt aggaatggca atatagaatg gattttacaa 2940
gatattaata gaaagtataa aagtttaatt tttgattata gtgaatcatt aagtcataca 3000
ggatatacaa ataaatggtt ttttgttact ataactaata atataatggg gtatatgaaa 3060
ctttatataa atggagaatt aaagcagagt gaaagaattg aagatttaaa tgaggttaag 3120
ttagataaaa ccatagtatt tggaatagat gagaatatag atgagaatca gatgctttgg 3180
attagagatt ttaatatttt ttctaaagaa ttaagcaatg aagatattaa tattgtatat 3240
gagggacaaa tattaagaaa tgttattaaa gattattggg gaaatccttt gaagtttgat 3300
acagaatatt atattattaa tgataattat atagataggt atatagcacc taaaagtaat 3360
atacttgtac ttgttcagta tccagataga tctaaattat atactggaaa tcctattact 3420
attaaatcag tatctgataa gaatccttat agtagaattt taaatggaga taatataatg 3480
tttcatatgt tatataatag tgggaaatat atgataataa gagatactga tacaatatat 3540
gcaatagaag gaagagagtg ttcaaaaaat tgtgtatatg cattaaaatt acagagtaat 3600
ttaggtaatt atggtatagg tatatttagt ataaaaaata ttgtatctca aaataaatat 3660
tgtagtcaaa ttttctctag ttttatgaaa aatacaatgc ttctagcaga tatatataaa 3720
ccttggagat tttcttttga aaatgcatac acgccagttg cagtaactaa ttatgagaca 3780
aaactattat caacttcatc tttttggaaa tttatttcta gggatccagg atgggtagag 3840
taa 3843
<210> 6
<211> 3617
<212> PRT
<213> Clostridium botulinum
<400> 6
Met Glu Thr Pro Arg Ile Leu Glu Thr His Arg Ile Leu Glu Ala Ser
1 5 10 15
Asn Ala Ser Asn Pro His Glu Ala Ser Asn Thr Tyr Arg Ser Glu Arg
20 25 30
Ala Ser Pro Pro Arg Val Ala Leu Ala Ser Pro Ala Ser Asn Leu Tyr
35 40 45
Ser Ala Ser Asn Ile Leu Glu Leu Glu Thr Tyr Arg Leu Glu Ala Ser
50 55 60
Pro Thr His Arg His Ile Ser Leu Glu Ala Ser Asn Thr His Arg Leu
65 70 75 80
Glu Ala Leu Ala Ala Ser Asn Gly Leu Pro Arg Gly Leu Leu Tyr Ser
85 90 95
Ala Leu Ala Pro His Glu Ala Arg Gly Ile Leu Glu Ile Leu Glu Gly
100 105 110
Leu Tyr Ala Ser Asn Ile Leu Glu Thr Arg Pro Val Ala Leu Ile Leu
115 120 125
Glu Pro Arg Ala Ser Pro Ala Arg Gly Pro His Glu Ser Glu Arg Ala
130 135 140
Arg Gly Ala Ser Pro Ser Glu Arg Ala Ser Asn Pro Arg Ala Ser Asn
145 150 155 160
Leu Glu Ala Ser Asn Leu Tyr Ser Pro Arg Pro Arg Ala Arg Gly Val
165 170 175
Ala Leu Thr His Arg Ser Glu Arg Pro Arg Leu Tyr Ser Ser Glu Arg
180 185 190
Gly Leu Tyr Thr Tyr Arg Thr Tyr Arg Ala Ser Pro Pro Arg Ala Ser
195 200 205
Asn Thr Tyr Arg Leu Glu Ser Glu Arg Thr His Arg Ala Ser Pro Ser
210 215 220
Glu Arg Gly Leu Leu Tyr Ser Ala Ser Pro Thr His Arg Pro His Glu
225 230 235 240
Leu Glu Leu Tyr Ser Gly Leu Ile Leu Glu Ile Leu Glu Leu Tyr Ser
245 250 255
Leu Glu Pro His Glu Leu Tyr Ser Ala Arg Gly Ile Leu Glu Ala Ser
260 265 270
Asn Ser Glu Arg Ala Arg Gly Gly Leu Ile Leu Glu Gly Leu Tyr Gly
275 280 285
Leu Gly Leu Leu Glu Ile Leu Glu Thr Tyr Arg Ala Arg Gly Leu Glu
290 295 300
Ala Leu Ala Thr His Arg Ala Ser Pro Ile Leu Glu Pro Arg Pro His
305 310 315 320
Glu Pro Arg Gly Leu Tyr Ala Ser Asn Ala Ser Asn Ala Ser Asn Thr
325 330 335
His Arg Pro Arg Ile Leu Glu Ala Ser Asn Thr His Arg Pro His Glu
340 345 350
Ala Ser Pro Pro His Glu Ala Ser Pro Val Ala Leu Ala Ser Pro Pro
355 360 365
His Glu Ala Ser Asn Ser Glu Arg Val Ala Leu Ala Ser Pro Val Ala
370 375 380
Leu Leu Tyr Ser Thr His Arg Ala Arg Gly Gly Leu Asn Gly Leu Tyr
385 390 395 400
Ala Ser Asn Ala Ser Asn Thr Arg Pro Val Ala Leu Leu Tyr Ser Thr
405 410 415
His Arg Gly Leu Tyr Ser Glu Arg Ile Leu Glu Ala Ser Asn Pro Arg
420 425 430
Ser Glu Arg Val Ala Leu Ile Leu Glu Ile Leu Glu Thr His Arg Gly
435 440 445
Leu Tyr Pro Arg Ala Arg Gly Gly Leu Ala Ser Asn Ile Leu Glu Ile
450 455 460
Leu Glu Ala Ser Pro Pro Arg Gly Leu Thr His Arg Ser Glu Arg Thr
465 470 475 480
His Arg Pro His Glu Leu Tyr Ser Leu Glu Thr His Arg Ala Ser Asn
485 490 495
Ala Ser Asn Thr His Arg Pro His Glu Ala Leu Ala Ala Leu Ala Gly
500 505 510
Leu Asn Gly Leu Gly Leu Tyr Pro His Glu Gly Leu Tyr Ala Leu Ala
515 520 525
Leu Glu Ser Glu Arg Ile Leu Glu Ile Leu Glu Ser Glu Arg Ile Leu
530 535 540
Glu Ser Glu Arg Pro Arg Ala Arg Gly Pro His Glu Met Glu Thr Leu
545 550 555 560
Glu Thr His Arg Thr Tyr Arg Ser Glu Arg Ala Ser Asn Ala Leu Ala
565 570 575
Thr His Arg Ala Ser Asn Ala Ser Asn Val Ala Leu Gly Leu Tyr Gly
580 585 590
Leu Gly Leu Tyr Ala Arg Gly Pro His Glu Ser Glu Arg Leu Tyr Ser
595 600 605
Ser Glu Arg Gly Leu Pro His Glu Cys Tyr Ser Met Glu Thr Ala Ser
610 615 620
Pro Pro Arg Ile Leu Glu Leu Glu Ile Leu Glu Leu Glu Met Glu Thr
625 630 635 640
His Ile Ser Gly Leu Leu Glu Ala Ser Asn His Ile Ser Ala Leu Ala
645 650 655
Met Glu Thr His Ile Ser Ala Ser Asn Leu Glu Thr Tyr Arg Gly Leu
660 665 670
Tyr Ile Leu Glu Ala Leu Ala Ile Leu Glu Pro Arg Ala Ser Asn Ala
675 680 685
Ser Pro Gly Leu Asn Ala Arg Gly Ile Leu Glu Ser Glu Arg Ser Glu
690 695 700
Arg Val Ala Leu Thr His Arg Ser Glu Arg Ala Ser Asn Ile Leu Glu
705 710 715 720
Pro His Glu Thr Tyr Arg Ser Glu Arg Gly Leu Asn Thr Tyr Arg Leu
725 730 735
Tyr Ser Val Ala Leu Leu Tyr Ser Leu Glu Gly Leu Thr Tyr Arg Ala
740 745 750
Leu Ala Gly Leu Ile Leu Glu Thr Tyr Arg Ala Leu Ala Pro His Glu
755 760 765
Gly Leu Tyr Gly Leu Tyr Pro Arg Thr His Arg Ile Leu Glu Ala Ser
770 775 780
Pro Leu Glu Ile Leu Glu Pro Arg Leu Tyr Ser Ser Glu Arg Ala Leu
785 790 795 800
Ala Ala Arg Gly Leu Tyr Ser Thr Tyr Arg Pro His Glu Gly Leu Gly
805 810 815
Leu Leu Tyr Ser Ala Leu Ala Leu Glu Ala Ser Pro Thr Tyr Arg Thr
820 825 830
Tyr Arg Ala Arg Gly Ser Glu Arg Ile Leu Glu Ala Leu Ala Leu Tyr
835 840 845
Ser Ala Arg Gly Leu Glu Ala Ser Asn Ser Glu Arg Ile Leu Glu Thr
850 855 860
His Arg Thr His Arg Ala Leu Ala Ala Ser Asn Pro Arg Ser Glu Arg
865 870 875 880
Ser Glu Arg Pro His Glu Ala Ser Asn Leu Tyr Ser Thr Tyr Arg Ile
885 890 895
Leu Glu Gly Leu Tyr Gly Leu Thr Tyr Arg Leu Tyr Ser Gly Leu Asn
900 905 910
Leu Tyr Ser Leu Glu Ile Leu Glu Ala Arg Gly Leu Tyr Ser Thr Tyr
915 920 925
Arg Ala Arg Gly Pro His Glu Val Ala Leu Val Ala Leu Gly Leu Ser
930 935 940
Glu Arg Ser Glu Arg Gly Leu Tyr Gly Leu Val Ala Leu Ala Leu Ala
945 950 955 960
Val Ala Leu Ala Ser Pro Ala Arg Gly Ala Ser Asn Leu Tyr Ser Pro
965 970 975
His Glu Ala Leu Ala Gly Leu Leu Glu Thr Tyr Arg Leu Tyr Ser Gly
980 985 990
Leu Leu Glu Thr His Arg Gly Leu Asn Ile Leu Glu Pro His Glu Thr
995 1000 1005
His Arg Gly Leu Pro His Glu Ala Ser Asn Thr Tyr Arg Ala Leu Ala
1010 1015 1020
Leu Tyr Ser Ile Leu Glu Thr Tyr Arg Ala Ser Asn Val Ala Leu Gly
1025 1030 1035 1040
Leu Asn Ala Ser Asn Ala Arg Gly Leu Tyr Ser Ile Leu Glu Thr Tyr
1045 1050 1055
Arg Leu Glu Ser Glu Arg Ala Ser Asn Val Ala Leu Thr Tyr Arg Thr
1060 1065 1070
His Arg Pro Arg Val Ala Leu Thr His Arg Ala Leu Ala Ala Ser Asn
1075 1080 1085
Ile Leu Glu Leu Glu Ala Ser Pro Ala Ser Pro Ala Ser Asn Val Ala
1090 1095 1100
Leu Thr Tyr Arg Ala Ser Pro Ile Leu Glu Gly Leu Asn Ala Ser Asn
1105 1110 1115 1120
Gly Leu Tyr Pro His Glu Ala Ser Asn Ile Leu Glu Pro Arg Leu Tyr
1125 1130 1135
Ser Ser Glu Arg Ala Ser Asn Leu Glu Ala Ser Asn Val Ala Leu Leu
1140 1145 1150
Glu Pro His Glu Met Glu Thr Gly Leu Tyr Gly Leu Asn Ala Ser Asn
1155 1160 1165
Leu Glu Ser Glu Arg Ala Arg Gly Ala Ser Asn Pro Arg Ala Leu Ala
1170 1175 1180
Leu Glu Ala Arg Gly Leu Tyr Ser Val Ala Leu Ala Ser Asn Pro Arg
1185 1190 1195 1200
Gly Leu Ala Ser Asn Met Glu Thr Leu Glu Thr Tyr Arg Leu Glu Pro
1205 1210 1215
His Glu Thr His Arg Leu Tyr Ser Pro His Glu Cys Tyr Ser His Ile
1220 1225 1230
Ser Leu Tyr Ser Ala Leu Ala Ile Leu Glu Ala Ser Pro Gly Leu Tyr
1235 1240 1245
Ala Arg Gly Ser Glu Arg Leu Glu Thr Tyr Arg Ala Ser Asn Leu Tyr
1250 1255 1260
Ser Thr His Arg Leu Glu Ala Ser Pro Cys Tyr Ser Ala Arg Gly Gly
1265 1270 1275 1280
Leu Leu Glu Leu Glu Val Ala Leu Leu Tyr Ser Ala Ser Asn Thr His
1285 1290 1295
Arg Ala Ser Pro Leu Glu Pro Arg Pro His Glu Ile Leu Glu Gly Leu
1300 1305 1310
Tyr Ala Ser Pro Ile Leu Glu Ser Glu Arg Ala Ser Pro Ile Leu Glu
1315 1320 1325
Leu Tyr Ser Thr His Arg Ala Ser Pro Ile Leu Glu Pro His Glu Leu
1330 1335 1340
Glu Ser Glu Arg Leu Tyr Ser Ala Ser Pro Ile Leu Glu Ala Ser Asn
1345 1350 1355 1360
Gly Leu Gly Leu Thr His Arg Gly Leu Val Ala Leu Ile Leu Glu Ala
1365 1370 1375
Ser Pro Thr Tyr Arg Pro Arg Ala Ser Pro Ala Ser Asn Val Ala Leu
1380 1385 1390
Ser Glu Arg Val Ala Leu Ala Ser Pro Gly Leu Asn Val Ala Leu Ile
1395 1400 1405
Leu Glu Leu Glu Ser Glu Arg Leu Tyr Ser Ala Ser Asn Thr His Arg
1410 1415 1420
Ser Glu Arg Gly Leu His Ile Ser Gly Leu Tyr Gly Leu Asn Leu Glu
1425 1430 1435 1440
Ala Ser Pro Leu Glu Leu Glu Thr Tyr Arg Pro Arg Ile Leu Glu Ile
1445 1450 1455
Leu Glu Gly Leu Gly Leu Tyr Gly Leu Ser Glu Arg Gly Leu Asn Val
1460 1465 1470
Ala Leu Leu Glu Pro Arg Gly Leu Tyr Gly Leu Ala Ser Asn Gly Leu
1475 1480 1485
Asn Val Ala Leu Pro His Glu Thr Tyr Arg Ala Ser Pro Ala Ser Asn
1490 1495 1500
Ala Arg Gly Thr His Arg Gly Leu Asn Ala Ser Asn Val Ala Leu Ala
1505 1510 1515 1520
Ser Pro Thr Tyr Arg Leu Glu Ala Ser Asn Ser Glu Arg Thr Tyr Arg
1525 1530 1535
Thr Tyr Arg Thr Tyr Arg Leu Glu Gly Leu Ser Glu Arg Gly Leu Asn
1540 1545 1550
Leu Tyr Ser Leu Glu Ser Glu Arg Ala Ser Pro Ala Ser Asn Val Ala
1555 1560 1565
Leu Gly Leu Ala Ser Pro Pro His Glu Thr His Arg Pro His Glu Thr
1570 1575 1580
His Arg Thr His Arg Ser Glu Arg Ile Leu Glu Gly Leu Gly Leu Ala
1585 1590 1595 1600
Leu Ala Leu Glu Ala Ser Pro Ala Ser Asn Ser Glu Arg Gly Leu Tyr
1605 1610 1615
Leu Tyr Ser Val Ala Leu Thr Tyr Arg Thr His Arg Thr Tyr Arg Pro
1620 1625 1630
His Glu Pro Arg Leu Tyr Ser Leu Glu Ala Leu Ala Ala Ser Pro Leu
1635 1640 1645
Tyr Ser Val Ala Leu Ala Ser Asn Thr His Arg Gly Leu Tyr Val Ala
1650 1655 1660
Leu Gly Leu Asn Gly Leu Tyr Gly Leu Tyr Leu Glu Pro His Glu Leu
1665 1670 1675 1680
Glu Met Glu Thr Thr Arg Pro Ala Leu Ala Ala Ser Asn Ala Ser Pro
1685 1690 1695
Val Ala Leu Val Ala Leu Gly Leu Ala Ser Pro Pro His Glu Thr His
1700 1705 1710
Arg Thr His Arg Ala Ser Asn Ile Leu Glu Leu Glu Ala Arg Gly Leu
1715 1720 1725
Tyr Ser Ala Ser Pro Thr His Arg Leu Glu Ala Ser Pro Leu Tyr Ser
1730 1735 1740
Ile Leu Glu Ser Glu Arg Ala Ser Pro Val Ala Leu Ser Glu Arg Ala
1745 1750 1755 1760
Leu Ala Ile Leu Glu Ile Leu Glu Pro Arg Thr Tyr Arg Ile Leu Glu
1765 1770 1775
Gly Leu Tyr Pro Arg Ala Leu Ala Leu Glu Ala Ser Asn Ile Leu Glu
1780 1785 1790
Ser Glu Arg Ala Ser Asn Ser Glu Arg Val Ala Leu Ala Arg Gly Ala
1795 1800 1805
Arg Gly Gly Leu Tyr Ala Ser Asn Pro His Glu Thr His Arg Gly Leu
1810 1815 1820
Ala Leu Ala Pro His Glu Ala Leu Ala Val Ala Leu Thr His Arg Gly
1825 1830 1835 1840
Leu Tyr Val Ala Leu Thr His Arg Ile Leu Glu Leu Glu Leu Glu Gly
1845 1850 1855
Leu Ala Leu Ala Pro His Glu Gly Leu Asn Gly Leu Pro His Glu Thr
1860 1865 1870
His Arg Ile Leu Glu Pro Arg Ala Leu Ala Leu Glu Gly Leu Tyr Ala
1875 1880 1885
Leu Ala Pro His Glu Val Ala Leu Ile Leu Glu Thr Tyr Arg Ser Glu
1890 1895 1900
Arg Leu Tyr Ser Val Ala Leu Gly Leu Asn Gly Leu Ala Arg Gly Ala
1905 1910 1915 1920
Ser Asn Gly Leu Ile Leu Glu Ile Leu Glu Leu Tyr Ser Thr His Arg
1925 1930 1935
Ile Leu Glu Ala Ser Pro Ala Ser Asn Cys Tyr Ser Leu Glu Gly Leu
1940 1945 1950
Gly Leu Asn Ala Arg Gly Ile Leu Glu Leu Tyr Ser Ala Arg Gly Thr
1955 1960 1965
Arg Pro Leu Tyr Ser Ala Ser Pro Ser Glu Arg Thr Tyr Arg Gly Leu
1970 1975 1980
Thr Arg Pro Met Glu Thr Ile Leu Glu Gly Leu Tyr Thr His Arg Thr
1985 1990 1995 2000
Arg Pro Leu Glu Ser Glu Arg Ala Arg Gly Ile Leu Glu Thr His Arg
2005 2010 2015
Thr His Arg Gly Leu Asn Pro His Glu Ala Ser Asn Ala Ser Asn Ile
2020 2025 2030
Leu Glu Ser Glu Arg Thr Tyr Arg Gly Leu Asn Met Glu Thr Thr Tyr
2035 2040 2045
Arg Ala Ser Pro Ser Glu Arg Leu Glu Ala Ser Asn Thr Tyr Arg Gly
2050 2055 2060
Leu Asn Ala Leu Ala Ala Ser Pro Ala Leu Ala Ile Leu Glu Leu Tyr
2065 2070 2075 2080
Ser Ala Ser Pro Leu Tyr Ser Ile Leu Glu Ala Ser Pro Leu Glu Gly
2085 2090 2095
Leu Thr Tyr Arg Leu Tyr Ser Leu Tyr Ser Thr Tyr Arg Ser Glu Arg
2100 2105 2110
Gly Leu Tyr Ser Glu Arg Ala Ser Pro Leu Tyr Ser Gly Leu Ala Ser
2115 2120 2125
Asn Ile Leu Glu Leu Tyr Ser Ser Glu Arg Gly Leu Asn Val Ala Leu
2130 2135 2140
Gly Leu Ala Ser Asn Leu Glu Leu Tyr Ser Ala Ser Asn Ser Glu Arg
2145 2150 2155 2160
Leu Glu Ala Ser Pro Ile Leu Glu Leu Tyr Ser Ile Leu Glu Ser Glu
2165 2170 2175
Arg Gly Leu Ala Leu Ala Met Glu Thr Ala Ser Asn Ala Ser Asn Ile
2180 2185 2190
Leu Glu Ala Ser Asn Leu Tyr Ser Pro His Glu Ile Leu Glu Ala Arg
2195 2200 2205
Gly Gly Leu Cys Tyr Ser Ser Glu Arg Val Ala Leu Thr His Arg Thr
2210 2215 2220
Tyr Arg Leu Glu Pro His Glu Leu Tyr Ser Ala Ser Asn Met Glu Thr
2225 2230 2235 2240
Leu Glu Pro Arg Leu Tyr Ser Val Ala Leu Ile Leu Glu Ala Ser Pro
2245 2250 2255
Gly Leu Leu Glu Ala Ser Asn Leu Tyr Ser Pro His Glu Ala Ser Pro
2260 2265 2270
Leu Glu Leu Tyr Ser Thr His Arg Leu Tyr Ser Thr His Arg Gly Leu
2275 2280 2285
Leu Glu Ile Leu Glu Ala Ser Asn Leu Glu Ile Leu Glu Ala Ser Pro
2290 2295 2300
Ser Glu Arg His Ile Ser Ala Ser Asn Ile Leu Glu Ile Leu Glu Leu
2305 2310 2315 2320
Glu Val Ala Leu Gly Leu Tyr Gly Leu Val Ala Leu Ala Ser Pro Ala
2325 2330 2335
Arg Gly Leu Glu Leu Tyr Ser Ala Leu Ala Leu Tyr Ser Val Ala Leu
2340 2345 2350
Ala Ser Asn Gly Leu Ser Glu Arg Pro His Glu Gly Leu Ala Ser Asn
2355 2360 2365
Thr His Arg Ile Leu Glu Pro Arg Pro His Glu Ala Ser Asn Ile Leu
2370 2375 2380
Glu Pro His Glu Ser Glu Arg Thr Tyr Arg Thr His Arg Ala Ser Asn
2385 2390 2395 2400
Ala Ser Asn Ser Glu Arg Leu Glu Leu Glu Leu Tyr Ser Ala Ser Pro
2405 2410 2415
Ile Leu Glu Ile Leu Glu Ala Ser Asn Gly Leu Thr Tyr Arg Pro His
2420 2425 2430
Glu Ala Ser Asn Ser Glu Arg Ile Leu Glu Ala Ser Asn Ala Ser Pro
2435 2440 2445
Ser Glu Arg Leu Tyr Ser Ile Leu Glu Leu Glu Ser Glu Arg Leu Glu
2450 2455 2460
Gly Leu Asn Ala Ser Asn Leu Tyr Ser Leu Tyr Ser Ala Ser Asn Ala
2465 2470 2475 2480
Leu Ala Leu Glu Val Ala Leu Ala Ser Pro Thr His Arg Ser Glu Arg
2485 2490 2495
Gly Leu Tyr Thr Tyr Arg Ala Ser Asn Ala Leu Ala Gly Leu Val Ala
2500 2505 2510
Leu Ala Arg Gly Leu Glu Gly Leu Gly Leu Tyr Ala Ser Pro Val Ala
2515 2520 2525
Leu Gly Leu Asn Val Ala Leu Ala Ser Asn Thr His Arg Ile Leu Glu
2530 2535 2540
Thr Tyr Arg Thr His Arg Ala Ser Asn Ala Ser Pro Pro His Glu Leu
2545 2550 2555 2560
Tyr Ser Leu Glu Ser Glu Arg Ser Glu Arg Ser Glu Arg Gly Leu Tyr
2565 2570 2575
Ala Ser Pro Leu Tyr Ser Ile Leu Glu Ile Leu Glu Val Ala Leu Ala
2580 2585 2590
Ser Asn Leu Glu Ala Ser Asn Ala Ser Asn Ala Ser Asn Ile Leu Glu
2595 2600 2605
Leu Glu Thr Tyr Arg Ser Glu Arg Ala Leu Ala Ile Leu Glu Thr Tyr
2610 2615 2620
Arg Gly Leu Ala Ser Asn Ser Glu Arg Ser Glu Arg Val Ala Leu Ser
2625 2630 2635 2640
Glu Arg Pro His Glu Thr Arg Pro Ile Leu Glu Leu Tyr Ser Ile Leu
2645 2650 2655
Glu Ser Glu Arg Leu Tyr Ser Ala Ser Pro Leu Glu Thr His Arg Ala
2660 2665 2670
Ser Asn Ser Glu Arg His Ile Ser Ala Ser Asn Gly Leu Thr Tyr Arg
2675 2680 2685
Thr His Arg Ile Leu Glu Ile Leu Glu Ala Ser Asn Ser Glu Arg Ile
2690 2695 2700
Leu Glu Leu Tyr Ser Gly Leu Asn Ala Ser Asn Ser Glu Arg Gly Leu
2705 2710 2715 2720
Tyr Thr Arg Pro Leu Tyr Ser Leu Glu Cys Tyr Ser Ile Leu Glu Ala
2725 2730 2735
Arg Gly Ala Ser Asn Gly Leu Tyr Ala Ser Asn Ile Leu Glu Gly Leu
2740 2745 2750
Thr Arg Pro Ile Leu Glu Leu Glu Gly Leu Asn Ala Ser Pro Ile Leu
2755 2760 2765
Glu Ala Ser Asn Ala Arg Gly Leu Tyr Ser Thr Tyr Arg Leu Tyr Ser
2770 2775 2780
Ser Glu Arg Leu Glu Ile Leu Glu Pro His Glu Ala Ser Pro Thr Tyr
2785 2790 2795 2800
Arg Ser Glu Arg Gly Leu Ser Glu Arg Leu Glu Ser Glu Arg His Ile
2805 2810 2815
Ser Thr His Arg Gly Leu Tyr Thr Tyr Arg Thr His Arg Ala Ser Asn
2820 2825 2830
Leu Tyr Ser Thr Arg Pro Pro His Glu Pro His Glu Val Ala Leu Thr
2835 2840 2845
His Arg Ile Leu Glu Thr His Arg Ala Ser Asn Ala Ser Asn Ile Leu
2850 2855 2860
Glu Met Glu Thr Gly Leu Tyr Thr Tyr Arg Met Glu Thr Leu Tyr Ser
2865 2870 2875 2880
Leu Glu Thr Tyr Arg Ile Leu Glu Ala Ser Asn Gly Leu Tyr Gly Leu
2885 2890 2895
Leu Glu Leu Tyr Ser Gly Leu Asn Ser Glu Arg Gly Leu Ala Arg Gly
2900 2905 2910
Ile Leu Glu Gly Leu Ala Ser Pro Leu Glu Ala Ser Asn Gly Leu Val
2915 2920 2925
Ala Leu Leu Tyr Ser Leu Glu Ala Ser Pro Leu Tyr Ser Thr His Arg
2930 2935 2940
Ile Leu Glu Val Ala Leu Pro His Glu Gly Leu Tyr Ile Leu Glu Ala
2945 2950 2955 2960
Ser Pro Gly Leu Ala Ser Asn Ile Leu Glu Ala Ser Pro Gly Leu Ala
2965 2970 2975
Ser Asn Gly Leu Asn Met Glu Thr Leu Glu Thr Arg Pro Ile Leu Glu
2980 2985 2990
Ala Arg Gly Ala Ser Pro Pro His Glu Ala Ser Asn Ile Leu Glu Pro
2995 3000 3005
His Glu Ser Glu Arg Leu Tyr Ser Gly Leu Leu Glu Ser Glu Arg Ala
3010 3015 3020
Ser Asn Gly Leu Ala Ser Pro Ile Leu Glu Ala Ser Asn Ile Leu Glu
3025 3030 3035 3040
Val Ala Leu Thr Tyr Arg Gly Leu Gly Leu Tyr Gly Leu Asn Ile Leu
3045 3050 3055
Glu Leu Glu Ala Arg Gly Ala Ser Asn Val Ala Leu Ile Leu Glu Leu
3060 3065 3070
Tyr Ser Ala Ser Pro Thr Tyr Arg Thr Arg Pro Gly Leu Tyr Ala Ser
3075 3080 3085
Asn Pro Arg Leu Glu Leu Tyr Ser Pro His Glu Ala Ser Pro Thr His
3090 3095 3100
Arg Gly Leu Thr Tyr Arg Thr Tyr Arg Ile Leu Glu Ile Leu Glu Ala
3105 3110 3115 3120
Ser Asn Ala Ser Pro Ala Ser Asn Thr Tyr Arg Ile Leu Glu Ala Ser
3125 3130 3135
Pro Ala Arg Gly Thr Tyr Arg Ile Leu Glu Ala Leu Ala Pro Arg Leu
3140 3145 3150
Tyr Ser Ser Glu Arg Ala Ser Asn Ile Leu Glu Leu Glu Val Ala Leu
3155 3160 3165
Leu Glu Val Ala Leu Gly Leu Asn Thr Tyr Arg Pro Arg Ala Ser Pro
3170 3175 3180
Ala Arg Gly Ser Glu Arg Leu Tyr Ser Leu Glu Thr Tyr Arg Thr His
3185 3190 3195 3200
Arg Gly Leu Tyr Ala Ser Asn Pro Arg Ile Leu Glu Thr His Arg Ile
3205 3210 3215
Leu Glu Leu Tyr Ser Ser Glu Arg Val Ala Leu Ser Glu Arg Ala Ser
3220 3225 3230
Pro Leu Tyr Ser Ala Ser Asn Pro Arg Thr Tyr Arg Ser Glu Arg Ala
3235 3240 3245
Arg Gly Ile Leu Glu Leu Glu Ala Ser Asn Gly Leu Tyr Ala Ser Pro
3250 3255 3260
Ala Ser Asn Ile Leu Glu Met Glu Thr Pro His Glu His Ile Ser Met
3265 3270 3275 3280
Glu Thr Leu Glu Thr Tyr Arg Ala Ser Asn Ser Glu Arg Gly Leu Tyr
3285 3290 3295
Leu Tyr Ser Thr Tyr Arg Met Glu Thr Ile Leu Glu Ile Leu Glu Ala
3300 3305 3310
Arg Gly Ala Ser Pro Thr His Arg Ala Ser Pro Thr His Arg Ile Leu
3315 3320 3325
Glu Thr Tyr Arg Ala Leu Ala Ile Leu Glu Gly Leu Gly Leu Tyr Ala
3330 3335 3340
Arg Gly Gly Leu Cys Tyr Ser Ser Glu Arg Leu Tyr Ser Ala Ser Asn
3345 3350 3355 3360
Cys Tyr Ser Val Ala Leu Thr Tyr Arg Ala Leu Ala Leu Glu Leu Tyr
3365 3370 3375
Ser Leu Glu Gly Leu Asn Ser Glu Arg Ala Ser Asn Leu Glu Gly Leu
3380 3385 3390
Tyr Ala Ser Asn Thr Tyr Arg Gly Leu Tyr Ile Leu Glu Gly Leu Tyr
3395 3400 3405
Ile Leu Glu Pro His Glu Ser Glu Arg Ile Leu Glu Leu Tyr Ser Ala
3410 3415 3420
Ser Asn Ile Leu Glu Val Ala Leu Ser Glu Arg Gly Leu Asn Ala Ser
3425 3430 3435 3440
Asn Leu Tyr Ser Thr Tyr Arg Cys Tyr Ser Ser Glu Arg Gly Leu Asn
3445 3450 3455
Ile Leu Glu Pro His Glu Ser Glu Arg Ser Glu Arg Pro His Glu Met
3460 3465 3470
Glu Thr Leu Tyr Ser Ala Ser Asn Thr His Arg Met Glu Thr Leu Glu
3475 3480 3485
Leu Glu Ala Leu Ala Ala Ser Pro Ile Leu Glu Thr Tyr Arg Leu Tyr
3490 3495 3500
Ser Pro Arg Thr Arg Pro Ala Arg Gly Pro His Glu Ser Glu Arg Pro
3505 3510 3515 3520
His Glu Gly Leu Ala Ser Asn Ala Leu Ala Thr Tyr Arg Thr His Arg
3525 3530 3535
Pro Arg Val Ala Leu Ala Leu Ala Val Ala Leu Thr His Arg Ala Ser
3540 3545 3550
Asn Thr Tyr Arg Gly Leu Thr His Arg Leu Tyr Ser Leu Glu Leu Glu
3555 3560 3565
Ser Glu Arg Thr His Arg Ser Glu Arg Ser Glu Arg Pro His Glu Thr
3570 3575 3580
Arg Pro Leu Tyr Ser Pro His Glu Ile Leu Glu Ser Glu Arg Ala Arg
3585 3590 3595 3600
Gly Ala Ser Pro Pro Arg Gly Leu Tyr Thr Arg Pro Val Ala Leu Gly
3605 3610 3615
Leu
<210> 7
<211> 3858
<212> DNA
<213> Clostridium botulinum
<400> 7
atgacatggc cagtaaaaga ttttaattat agtgatcctg ttaatgacaa tgatatatta 60
tatttaagaa taccacaaaa taagttaatt actacacctg taaaagcttt tatgattact 120
caaaatattt gggtaatacc agaaagattt tcatcagata ctaatccaag tttaagtaaa 180
ccgcctagac ctacttcaaa gtatcaaagt tattatgatc ctagttattt atctactgat 240
gagcaaaaag atacattttt aaaagggatt ataaaattat ttaaaagaat taatgaaaga 300
gatataggaa aaaaattaat aaattattta gtagttggtt caccttttat gggagattca 360
agtacgcctg aagatacatt tgattttaca cgtcatacta ctaatattgc agttgaaaag 420
tttgaaaatg gtagttggaa agtaacaaat attataacac caagtgtatt gatatttgga 480
ccacttccta atatattaga ctatacagca tcccttacat tgcaaggaca acaatcaaat 540
ccatcatttg aagggtttgg aacattatct atactaaaag tagcacctga atttttgtta 600
acatttagtg atgtaacatc taatcaaagt tcagctgtat taggcaaatc tatattttgt 660
atggatccag taatagcttt aatgcatgag ttaacacatt ctttgcatca attgtatgga 720
ataaatatac catctgataa aaggattcgt ccacaagtta gcgagggatt tttttctcaa 780
gatggaccca acgtacaatt tgaggaatta tacacatttg gaggatcaga tgttgaaata 840
atacctcaaa ttgaaagatt acaattaaga gaaaaagcat taggtcacta taaagatata 900
gcgaaaagac ttaataatat taataaaact attccttcta gttggagtag taatatagat 960
aaatataaaa aaatattttc tgaaaagtat aattttgata aagataatac aggaaatttt 1020
gttgtaaata ttgataaatt caatagctta tattcagact tgactaatgt tatgtcagaa 1080
gttgtttatt cttcgcaata taatgttaaa aacaggactc attatttttc aaagcattat 1140
ctacctgtat ttgcaaatat attagatgat aatatttata ctataataaa cggttttaat 1200
ttaacaacta aaggttttaa tatagaaaat tcgggtcaga atatagaaag gaatcctgca 1260
ctacaaaaac ttagttcaga aagtgtagta gatttgttta caaaagtatg tttaagatta 1320
acaagaaata gtagagatga ttcaacatgt attcaagtta aaaataatac attaccttat 1380
gtagctgata aagatagcat ttcacaagaa atatttgaaa gtcaaattat tacagatgag 1440
actaatgtag aaaattattc agataatttt tcattagatg aatctatttt agatgcaaaa 1500
gtccctacta atcctgaagc agtagatcca ctgttaccca atgttaatat ggaaccttta 1560
aatgttccag gtgaagaaga agtattttat gatgatatta ctaaagatgt tgattattta 1620
aactcttatt attatttgga agcccaaaaa ttaagtaata atgttgaaaa tattactctt 1680
acaacttcag ttgaagaagc attaggttat agcaataaga tatacacatt tttacctagc 1740
ttagctgaaa aagtgaataa aggtgttcaa gcaggtttat tcttaaattg ggcgaatgaa 1800
gtagttgagg attttactac aaatattatg aaaaaagata cattggataa aatatcagat 1860
gtatcagcca taattccata tataggacct gccttaaata taggaaattc agcattaagg 1920
ggaaacttta agcaagcatt tgcaacagct ggtgtagctt ttttgttaga aggatttcca 1980
gagtttacaa tacctgcact cggtgtattt accttttata gttctattca agaaagagag 2040
aaaattatta aaactataga aaattgttta gaacaaagag ttaagagatg gaaagattca 2100
tatcaatgga tggtatcaaa ttggttgtca agaattacta ctcgatttaa tcatataagt 2160
tatcaaatgt atgattcttt gagttatcag gcagatgcaa tcaaagctaa aatagattta 2220
gaatataaaa aatactcagg aagtgataaa gaaaatataa aaagtcaagt tgaaaattta 2280
aaaaatagtt tagatgtaaa aatctcggaa gcaatgaata atataaataa atttatacga 2340
gaatgttctg taacatactt atttaaaaat atgctcccta aagtaattga tgaattaaat 2400
aagtttgatt taaaaactaa aacagaatta attaatctta tagatagtca taatattatt 2460
ctagttggtg aagtagatag attaaaagca aaagtaaatg agagttttga aaatacaata 2520
ccctttaata ttttttcata tactaataat tctttattaa aagatatgat taatgaatat 2580
ttcaatagta ttaatgattc aaaaattttg agcttacaaa ataaaaaaaa tactttgatg 2640
gatacatcag gatataacgc agaagtgaga gtagaaggca atgttcagct taatccaata 2700
tttccatttg actttaaatt aggtagttca ggggatgata gaggtaaagt tatagtaacc 2760
cagaatgaaa atattgtata taatgctatg tatgaaagtt ttagtattag tttttggatt 2820
aggataaata aatgggtaag taatttacct ggatatacta taattgatag tgttaaaaat 2880
aactcaggtt ggagtatagg tattattagt aattttttag tgtttacttt aaaacaaaat 2940
gaaaatagtg aacaagatat aaactttagt tatgatatat caaagaatgc tgcgggatat 3000
aataaatggt tttttgtaac tattactacc aatatgatgg gaaatatgat gatttatata 3060
aatggaaaat taatagatac tataaaagtt aaagagttaa ctggaattaa ttttagcaaa 3120
actataacat ttcaaatgaa taaaattcca aatactggct taattacctc agattctgat 3180
aacatcaata tgtggataag ggatttttat atctttgcta aagaattaga tgataaagat 3240
attaatatat tatttaatag cttgcaatat actaatgttg taaaagatta ttggggaaat 3300
gatttaagat atgataaaga atattacatg attaacgtaa attatatgaa tagatatatg 3360
tctaaaaaag gcaatggaat tgtttttaat acacgtaaaa ataataatga cttcaatgaa 3420
ggatataaaa ttataataaa aagaattaga ggaaatacaa atgatactag agtacgagga 3480
gaaaatgtat tatattttaa tactacaatt gataacaaac aatatagttt aggtatgtat 3540
aaaccttcta gaaatctagg gactgattta gttccactag gtgcattgga tcaaccaatg 3600
gatgagatac gtaaatatgg ttcgtttata atacaaccat gcaatacttt tgattactat 3660
gcatcacaat tatttttgtc aagtaatgca acaacaaata ggcttggaat actatcaatt 3720
ggtagttata gtttcaaact tggagatgac tattggttta atcacgaata tttaattcct 3780
gttataaaaa tagagcatta tgcttcatta ttagaatcaa catcaactca ttgggttttt 3840
gtacctgcaa gtgaataa 3858
<210> 8
<211> 3632
<212> PRT
<213> Clostridium botulinum
<400> 8
Met Glu Thr Thr His Arg Thr Arg Pro Pro Arg Val Ala Leu Leu Tyr
1 5 10 15
Ser Ala Ser Pro Pro His Glu Ala Ser Asn Thr Tyr Arg Ser Glu Arg
20 25 30
Ala Ser Pro Pro Arg Val Ala Leu Ala Ser Asn Ala Ser Pro Ala Ser
35 40 45
Asn Ala Ser Pro Ile Leu Glu Leu Glu Thr Tyr Arg Leu Glu Ala Arg
50 55 60
Gly Ile Leu Glu Pro Arg Gly Leu Asn Ala Ser Asn Leu Tyr Ser Leu
65 70 75 80
Glu Ile Leu Glu Thr His Arg Thr His Arg Pro Arg Val Ala Leu Leu
85 90 95
Tyr Ser Ala Leu Ala Pro His Glu Met Glu Thr Ile Leu Glu Thr His
100 105 110
Arg Gly Leu Asn Ala Ser Asn Ile Leu Glu Thr Arg Pro Val Ala Leu
115 120 125
Ile Leu Glu Pro Arg Gly Leu Ala Arg Gly Pro His Glu Ser Glu Arg
130 135 140
Ser Glu Arg Ala Ser Pro Thr His Arg Ala Ser Asn Pro Arg Ser Glu
145 150 155 160
Arg Leu Glu Ser Glu Arg Leu Tyr Ser Pro Arg Pro Arg Ala Arg Gly
165 170 175
Pro Arg Thr His Arg Ser Glu Arg Leu Tyr Ser Thr Tyr Arg Gly Leu
180 185 190
Asn Ser Glu Arg Thr Tyr Arg Thr Tyr Arg Ala Ser Pro Pro Arg Ser
195 200 205
Glu Arg Thr Tyr Arg Leu Glu Ser Glu Arg Thr His Arg Ala Ser Pro
210 215 220
Gly Leu Gly Leu Asn Leu Tyr Ser Ala Ser Pro Thr His Arg Pro His
225 230 235 240
Glu Leu Glu Leu Tyr Ser Gly Leu Tyr Ile Leu Glu Ile Leu Glu Leu
245 250 255
Tyr Ser Leu Glu Pro His Glu Leu Tyr Ser Ala Arg Gly Ile Leu Glu
260 265 270
Ala Ser Asn Gly Leu Ala Arg Gly Ala Ser Pro Ile Leu Glu Gly Leu
275 280 285
Tyr Leu Tyr Ser Leu Tyr Ser Leu Glu Ile Leu Glu Ala Ser Asn Thr
290 295 300
Tyr Arg Leu Glu Val Ala Leu Val Ala Leu Gly Leu Tyr Ser Glu Arg
305 310 315 320
Pro Arg Pro His Glu Met Glu Thr Gly Leu Tyr Ala Ser Pro Ser Glu
325 330 335
Arg Ser Glu Arg Thr His Arg Pro Arg Gly Leu Ala Ser Pro Thr His
340 345 350
Arg Pro His Glu Ala Ser Pro Pro His Glu Thr His Arg Ala Arg Gly
355 360 365
His Ile Ser Thr His Arg Thr His Arg Ala Ser Asn Ile Leu Glu Ala
370 375 380
Leu Ala Val Ala Leu Gly Leu Leu Tyr Ser Pro His Glu Gly Leu Ala
385 390 395 400
Ser Asn Gly Leu Tyr Ser Glu Arg Thr Arg Pro Leu Tyr Ser Val Ala
405 410 415
Leu Thr His Arg Ala Ser Asn Ile Leu Glu Ile Leu Glu Thr His Arg
420 425 430
Pro Arg Ser Glu Arg Val Ala Leu Leu Glu Ile Leu Glu Pro His Glu
435 440 445
Gly Leu Tyr Pro Arg Leu Glu Pro Arg Ala Ser Asn Ile Leu Glu Leu
450 455 460
Glu Ala Ser Pro Thr Tyr Arg Thr His Arg Ala Leu Ala Ser Glu Arg
465 470 475 480
Leu Glu Thr His Arg Leu Glu Gly Leu Asn Gly Leu Tyr Gly Leu Asn
485 490 495
Gly Leu Asn Ser Glu Arg Ala Ser Asn Pro Arg Ser Glu Arg Pro His
500 505 510
Glu Gly Leu Gly Leu Tyr Pro His Glu Gly Leu Tyr Thr His Arg Leu
515 520 525
Glu Ser Glu Arg Ile Leu Glu Leu Glu Leu Tyr Ser Val Ala Leu Ala
530 535 540
Leu Ala Pro Arg Gly Leu Pro His Glu Leu Glu Leu Glu Thr His Arg
545 550 555 560
Pro His Glu Ser Glu Arg Ala Ser Pro Val Ala Leu Thr His Arg Ser
565 570 575
Glu Arg Ala Ser Asn Gly Leu Asn Ser Glu Arg Ser Glu Arg Ala Leu
580 585 590
Ala Val Ala Leu Leu Glu Gly Leu Tyr Leu Tyr Ser Ser Glu Arg Ile
595 600 605
Leu Glu Pro His Glu Cys Tyr Ser Met Glu Thr Ala Ser Pro Pro Arg
610 615 620
Val Ala Leu Ile Leu Glu Ala Leu Ala Leu Glu Met Glu Thr His Ile
625 630 635 640
Ser Gly Leu Leu Glu Thr His Arg His Ile Ser Ser Glu Arg Leu Glu
645 650 655
His Ile Ser Gly Leu Asn Leu Glu Thr Tyr Arg Gly Leu Tyr Ile Leu
660 665 670
Glu Ala Ser Asn Ile Leu Glu Pro Arg Ser Glu Arg Ala Ser Pro Leu
675 680 685
Tyr Ser Ala Arg Gly Ile Leu Glu Ala Arg Gly Pro Arg Gly Leu Asn
690 695 700
Val Ala Leu Ser Glu Arg Gly Leu Gly Leu Tyr Pro His Glu Pro His
705 710 715 720
Glu Ser Glu Arg Gly Leu Asn Ala Ser Pro Gly Leu Tyr Pro Arg Ala
725 730 735
Ser Asn Val Ala Leu Gly Leu Asn Pro His Glu Gly Leu Gly Leu Leu
740 745 750
Glu Thr Tyr Arg Thr His Arg Pro His Glu Gly Leu Tyr Gly Leu Tyr
755 760 765
Ser Glu Arg Ala Ser Pro Val Ala Leu Gly Leu Ile Leu Glu Ile Leu
770 775 780
Glu Pro Arg Gly Leu Asn Ile Leu Glu Gly Leu Ala Arg Gly Leu Glu
785 790 795 800
Gly Leu Asn Leu Glu Ala Arg Gly Gly Leu Leu Tyr Ser Ala Leu Ala
805 810 815
Leu Glu Gly Leu Tyr His Ile Ser Thr Tyr Arg Leu Tyr Ser Ala Ser
820 825 830
Pro Ile Leu Glu Ala Leu Ala Leu Tyr Ser Ala Arg Gly Leu Glu Ala
835 840 845
Ser Asn Ala Ser Asn Ile Leu Glu Ala Ser Asn Leu Tyr Ser Thr His
850 855 860
Arg Ile Leu Glu Pro Arg Ser Glu Arg Ser Glu Arg Thr Arg Pro Ser
865 870 875 880
Glu Arg Ser Glu Arg Ala Ser Asn Ile Leu Glu Ala Ser Pro Leu Tyr
885 890 895
Ser Thr Tyr Arg Leu Tyr Ser Leu Tyr Ser Ile Leu Glu Pro His Glu
900 905 910
Ser Glu Arg Gly Leu Leu Tyr Ser Thr Tyr Arg Ala Ser Asn Pro His
915 920 925
Glu Ala Ser Pro Leu Tyr Ser Ala Ser Pro Ala Ser Asn Thr His Arg
930 935 940
Gly Leu Tyr Ala Ser Asn Pro His Glu Val Ala Leu Val Ala Leu Ala
945 950 955 960
Ser Asn Ile Leu Glu Ala Ser Pro Leu Tyr Ser Pro His Glu Ala Ser
965 970 975
Asn Ser Glu Arg Leu Glu Thr Tyr Arg Ser Glu Arg Ala Ser Pro Leu
980 985 990
Glu Thr His Arg Ala Ser Asn Val Ala Leu Met Glu Thr Ser Glu Arg
995 1000 1005
Gly Leu Val Ala Leu Val Ala Leu Thr Tyr Arg Ser Glu Arg Ser Glu
1010 1015 1020
Arg Gly Leu Asn Thr Tyr Arg Ala Ser Asn Val Ala Leu Leu Tyr Ser
1025 1030 1035 1040
Ala Ser Asn Ala Arg Gly Thr His Arg His Ile Ser Thr Tyr Arg Pro
1045 1050 1055
His Glu Ser Glu Arg Leu Tyr Ser His Ile Ser Thr Tyr Arg Leu Glu
1060 1065 1070
Pro Arg Val Ala Leu Pro His Glu Ala Leu Ala Ala Ser Asn Ile Leu
1075 1080 1085
Glu Leu Glu Ala Ser Pro Ala Ser Pro Ala Ser Asn Ile Leu Glu Thr
1090 1095 1100
Tyr Arg Thr His Arg Ile Leu Glu Ile Leu Glu Ala Ser Asn Gly Leu
1105 1110 1115 1120
Tyr Pro His Glu Ala Ser Asn Leu Glu Thr His Arg Thr His Arg Leu
1125 1130 1135
Tyr Ser Gly Leu Tyr Pro His Glu Ala Ser Asn Ile Leu Glu Gly Leu
1140 1145 1150
Ala Ser Asn Ser Glu Arg Gly Leu Tyr Gly Leu Asn Ala Ser Asn Ile
1155 1160 1165
Leu Glu Gly Leu Ala Arg Gly Ala Ser Asn Pro Arg Ala Leu Ala Leu
1170 1175 1180
Glu Gly Leu Asn Leu Tyr Ser Leu Glu Ser Glu Arg Ser Glu Arg Gly
1185 1190 1195 1200
Leu Ser Glu Arg Val Ala Leu Val Ala Leu Ala Ser Pro Leu Glu Pro
1205 1210 1215
His Glu Thr His Arg Leu Tyr Ser Val Ala Leu Cys Tyr Ser Leu Glu
1220 1225 1230
Ala Arg Gly Leu Glu Thr His Arg Ala Arg Gly Ala Ser Asn Ser Glu
1235 1240 1245
Arg Ala Arg Gly Ala Ser Pro Ala Ser Pro Ser Glu Arg Thr His Arg
1250 1255 1260
Cys Tyr Ser Ile Leu Glu Gly Leu Asn Val Ala Leu Leu Tyr Ser Ala
1265 1270 1275 1280
Ser Asn Ala Ser Asn Thr His Arg Leu Glu Pro Arg Thr Tyr Arg Val
1285 1290 1295
Ala Leu Ala Leu Ala Ala Ser Pro Leu Tyr Ser Ala Ser Pro Ser Glu
1300 1305 1310
Arg Ile Leu Glu Ser Glu Arg Gly Leu Asn Gly Leu Ile Leu Glu Pro
1315 1320 1325
His Glu Gly Leu Ser Glu Arg Gly Leu Asn Ile Leu Glu Ile Leu Glu
1330 1335 1340
Thr His Arg Ala Ser Pro Gly Leu Thr His Arg Ala Ser Asn Val Ala
1345 1350 1355 1360
Leu Gly Leu Ala Ser Asn Thr Tyr Arg Ser Glu Arg Ala Ser Pro Ala
1365 1370 1375
Ser Asn Pro His Glu Ser Glu Arg Leu Glu Ala Ser Pro Gly Leu Ser
1380 1385 1390
Glu Arg Ile Leu Glu Leu Glu Ala Ser Pro Ala Leu Ala Leu Tyr Ser
1395 1400 1405
Val Ala Leu Pro Arg Thr His Arg Ala Ser Asn Pro Arg Gly Leu Ala
1410 1415 1420
Leu Ala Val Ala Leu Ala Ser Pro Pro Arg Leu Glu Leu Glu Pro Arg
1425 1430 1435 1440
Ala Ser Asn Val Ala Leu Ala Ser Asn Met Glu Thr Gly Leu Pro Arg
1445 1450 1455
Leu Glu Ala Ser Asn Val Ala Leu Pro Arg Gly Leu Tyr Gly Leu Gly
1460 1465 1470
Leu Gly Leu Val Ala Leu Pro His Glu Thr Tyr Arg Ala Ser Pro Ala
1475 1480 1485
Ser Pro Ile Leu Glu Thr His Arg Leu Tyr Ser Ala Ser Pro Val Ala
1490 1495 1500
Leu Ala Ser Pro Thr Tyr Arg Leu Glu Ala Ser Asn Ser Glu Arg Thr
1505 1510 1515 1520
Tyr Arg Thr Tyr Arg Thr Tyr Arg Leu Glu Gly Leu Ala Leu Ala Gly
1525 1530 1535
Leu Asn Leu Tyr Ser Leu Glu Ser Glu Arg Ala Ser Asn Ala Ser Asn
1540 1545 1550
Val Ala Leu Gly Leu Ala Ser Asn Ile Leu Glu Thr His Arg Leu Glu
1555 1560 1565
Thr His Arg Thr His Arg Ser Glu Arg Val Ala Leu Gly Leu Gly Leu
1570 1575 1580
Ala Leu Ala Leu Glu Gly Leu Tyr Thr Tyr Arg Ser Glu Arg Ala Ser
1585 1590 1595 1600
Asn Leu Tyr Ser Ile Leu Glu Thr Tyr Arg Thr His Arg Pro His Glu
1605 1610 1615
Leu Glu Pro Arg Ser Glu Arg Leu Glu Ala Leu Ala Gly Leu Leu Tyr
1620 1625 1630
Ser Val Ala Leu Ala Ser Asn Leu Tyr Ser Gly Leu Tyr Val Ala Leu
1635 1640 1645
Gly Leu Asn Ala Leu Ala Gly Leu Tyr Leu Glu Pro His Glu Leu Glu
1650 1655 1660
Ala Ser Asn Thr Arg Pro Ala Leu Ala Ala Ser Asn Gly Leu Val Ala
1665 1670 1675 1680
Leu Val Ala Leu Gly Leu Ala Ser Pro Pro His Glu Thr His Arg Thr
1685 1690 1695
His Arg Ala Ser Asn Ile Leu Glu Met Glu Thr Leu Tyr Ser Leu Tyr
1700 1705 1710
Ser Ala Ser Pro Thr His Arg Leu Glu Ala Ser Pro Leu Tyr Ser Ile
1715 1720 1725
Leu Glu Ser Glu Arg Ala Ser Pro Val Ala Leu Ser Glu Arg Ala Leu
1730 1735 1740
Ala Ile Leu Glu Ile Leu Glu Pro Arg Thr Tyr Arg Ile Leu Glu Gly
1745 1750 1755 1760
Leu Tyr Pro Arg Ala Leu Ala Leu Glu Ala Ser Asn Ile Leu Glu Gly
1765 1770 1775
Leu Tyr Ala Ser Asn Ser Glu Arg Ala Leu Ala Leu Glu Ala Arg Gly
1780 1785 1790
Gly Leu Tyr Ala Ser Asn Pro His Glu Leu Tyr Ser Gly Leu Asn Ala
1795 1800 1805
Leu Ala Pro His Glu Ala Leu Ala Thr His Arg Ala Leu Ala Gly Leu
1810 1815 1820
Tyr Val Ala Leu Ala Leu Ala Pro His Glu Leu Glu Leu Glu Gly Leu
1825 1830 1835 1840
Gly Leu Tyr Pro His Glu Pro Arg Gly Leu Pro His Glu Thr His Arg
1845 1850 1855
Ile Leu Glu Pro Arg Ala Leu Ala Leu Glu Gly Leu Tyr Val Ala Leu
1860 1865 1870
Pro His Glu Thr His Arg Pro His Glu Thr Tyr Arg Ser Glu Arg Ser
1875 1880 1885
Glu Arg Ile Leu Glu Gly Leu Asn Gly Leu Ala Arg Gly Gly Leu Leu
1890 1895 1900
Tyr Ser Ile Leu Glu Ile Leu Glu Leu Tyr Ser Thr His Arg Ile Leu
1905 1910 1915 1920
Glu Gly Leu Ala Ser Asn Cys Tyr Ser Leu Glu Gly Leu Gly Leu Asn
1925 1930 1935
Ala Arg Gly Val Ala Leu Leu Tyr Ser Ala Arg Gly Thr Arg Pro Leu
1940 1945 1950
Tyr Ser Ala Ser Pro Ser Glu Arg Thr Tyr Arg Gly Leu Asn Thr Arg
1955 1960 1965
Pro Met Glu Thr Val Ala Leu Ser Glu Arg Ala Ser Asn Thr Arg Pro
1970 1975 1980
Leu Glu Ser Glu Arg Ala Arg Gly Ile Leu Glu Thr His Arg Thr His
1985 1990 1995 2000
Arg Ala Arg Gly Pro His Glu Ala Ser Asn His Ile Ser Ile Leu Glu
2005 2010 2015
Ser Glu Arg Thr Tyr Arg Gly Leu Asn Met Glu Thr Thr Tyr Arg Ala
2020 2025 2030
Ser Pro Ser Glu Arg Leu Glu Ser Glu Arg Thr Tyr Arg Gly Leu Asn
2035 2040 2045
Ala Leu Ala Ala Ser Pro Ala Leu Ala Ile Leu Glu Leu Tyr Ser Ala
2050 2055 2060
Leu Ala Leu Tyr Ser Ile Leu Glu Ala Ser Pro Leu Glu Gly Leu Thr
2065 2070 2075 2080
Tyr Arg Leu Tyr Ser Leu Tyr Ser Thr Tyr Arg Ser Glu Arg Gly Leu
2085 2090 2095
Tyr Ser Glu Arg Ala Ser Pro Leu Tyr Ser Gly Leu Ala Ser Asn Ile
2100 2105 2110
Leu Glu Leu Tyr Ser Ser Glu Arg Gly Leu Asn Val Ala Leu Gly Leu
2115 2120 2125
Ala Ser Asn Leu Glu Leu Tyr Ser Ala Ser Asn Ser Glu Arg Leu Glu
2130 2135 2140
Ala Ser Pro Val Ala Leu Leu Tyr Ser Ile Leu Glu Ser Glu Arg Gly
2145 2150 2155 2160
Leu Ala Leu Ala Met Glu Thr Ala Ser Asn Ala Ser Asn Ile Leu Glu
2165 2170 2175
Ala Ser Asn Leu Tyr Ser Pro His Glu Ile Leu Glu Ala Arg Gly Gly
2180 2185 2190
Leu Cys Tyr Ser Ser Glu Arg Val Ala Leu Thr His Arg Thr Tyr Arg
2195 2200 2205
Leu Glu Pro His Glu Leu Tyr Ser Ala Ser Asn Met Glu Thr Leu Glu
2210 2215 2220
Pro Arg Leu Tyr Ser Val Ala Leu Ile Leu Glu Ala Ser Pro Gly Leu
2225 2230 2235 2240
Leu Glu Ala Ser Asn Leu Tyr Ser Pro His Glu Ala Ser Pro Leu Glu
2245 2250 2255
Leu Tyr Ser Thr His Arg Leu Tyr Ser Thr His Arg Gly Leu Leu Glu
2260 2265 2270
Ile Leu Glu Ala Ser Asn Leu Glu Ile Leu Glu Ala Ser Pro Ser Glu
2275 2280 2285
Arg His Ile Ser Ala Ser Asn Ile Leu Glu Ile Leu Glu Leu Glu Val
2290 2295 2300
Ala Leu Gly Leu Tyr Gly Leu Val Ala Leu Ala Ser Pro Ala Arg Gly
2305 2310 2315 2320
Leu Glu Leu Tyr Ser Ala Leu Ala Leu Tyr Ser Val Ala Leu Ala Ser
2325 2330 2335
Asn Gly Leu Ser Glu Arg Pro His Glu Gly Leu Ala Ser Asn Thr His
2340 2345 2350
Arg Ile Leu Glu Pro Arg Pro His Glu Ala Ser Asn Ile Leu Glu Pro
2355 2360 2365
His Glu Ser Glu Arg Thr Tyr Arg Thr His Arg Ala Ser Asn Ala Ser
2370 2375 2380
Asn Ser Glu Arg Leu Glu Leu Glu Leu Tyr Ser Ala Ser Pro Met Glu
2385 2390 2395 2400
Thr Ile Leu Glu Ala Ser Asn Gly Leu Thr Tyr Arg Pro His Glu Ala
2405 2410 2415
Ser Asn Ser Glu Arg Ile Leu Glu Ala Ser Asn Ala Ser Pro Ser Glu
2420 2425 2430
Arg Leu Tyr Ser Ile Leu Glu Leu Glu Ser Glu Arg Leu Glu Gly Leu
2435 2440 2445
Asn Ala Ser Asn Leu Tyr Ser Leu Tyr Ser Ala Ser Asn Thr His Arg
2450 2455 2460
Leu Glu Met Glu Thr Ala Ser Pro Thr His Arg Ser Glu Arg Gly Leu
2465 2470 2475 2480
Tyr Thr Tyr Arg Ala Ser Asn Ala Leu Ala Gly Leu Val Ala Leu Ala
2485 2490 2495
Arg Gly Val Ala Leu Gly Leu Gly Leu Tyr Ala Ser Asn Val Ala Leu
2500 2505 2510
Gly Leu Asn Leu Glu Ala Ser Asn Pro Arg Ile Leu Glu Pro His Glu
2515 2520 2525
Pro Arg Pro His Glu Ala Ser Pro Pro His Glu Leu Tyr Ser Leu Glu
2530 2535 2540
Gly Leu Tyr Ser Glu Arg Ser Glu Arg Gly Leu Tyr Ala Ser Pro Ala
2545 2550 2555 2560
Ser Pro Ala Arg Gly Gly Leu Tyr Leu Tyr Ser Val Ala Leu Ile Leu
2565 2570 2575
Glu Val Ala Leu Thr His Arg Gly Leu Asn Ala Ser Asn Gly Leu Ala
2580 2585 2590
Ser Asn Ile Leu Glu Val Ala Leu Thr Tyr Arg Ala Ser Asn Ala Leu
2595 2600 2605
Ala Met Glu Thr Thr Tyr Arg Gly Leu Ser Glu Arg Pro His Glu Ser
2610 2615 2620
Glu Arg Ile Leu Glu Ser Glu Arg Pro His Glu Thr Arg Pro Ile Leu
2625 2630 2635 2640
Glu Ala Arg Gly Ile Leu Glu Ala Ser Asn Leu Tyr Ser Thr Arg Pro
2645 2650 2655
Val Ala Leu Ser Glu Arg Ala Ser Asn Leu Glu Pro Arg Gly Leu Tyr
2660 2665 2670
Thr Tyr Arg Thr His Arg Ile Leu Glu Ile Leu Glu Ala Ser Pro Ser
2675 2680 2685
Glu Arg Val Ala Leu Leu Tyr Ser Ala Ser Asn Ala Ser Asn Ser Glu
2690 2695 2700
Arg Gly Leu Tyr Thr Arg Pro Ser Glu Arg Ile Leu Glu Gly Leu Tyr
2705 2710 2715 2720
Ile Leu Glu Ile Leu Glu Ser Glu Arg Ala Ser Asn Pro His Glu Leu
2725 2730 2735
Glu Val Ala Leu Pro His Glu Thr His Arg Leu Glu Leu Tyr Ser Gly
2740 2745 2750
Leu Asn Ala Ser Asn Gly Leu Ala Ser Asn Ser Glu Arg Gly Leu Gly
2755 2760 2765
Leu Asn Ala Ser Pro Ile Leu Glu Ala Ser Asn Pro His Glu Ser Glu
2770 2775 2780
Arg Thr Tyr Arg Ala Ser Pro Ile Leu Glu Ser Glu Arg Leu Tyr Ser
2785 2790 2795 2800
Ala Ser Asn Ala Leu Ala Ala Leu Ala Gly Leu Tyr Thr Tyr Arg Ala
2805 2810 2815
Ser Asn Leu Tyr Ser Thr Arg Pro Pro His Glu Pro His Glu Val Ala
2820 2825 2830
Leu Thr His Arg Ile Leu Glu Thr His Arg Thr His Arg Ala Ser Asn
2835 2840 2845
Met Glu Thr Met Glu Thr Gly Leu Tyr Ala Ser Asn Met Glu Thr Met
2850 2855 2860
Glu Thr Ile Leu Glu Thr Tyr Arg Ile Leu Glu Ala Ser Asn Gly Leu
2865 2870 2875 2880
Tyr Leu Tyr Ser Leu Glu Ile Leu Glu Ala Ser Pro Thr His Arg Ile
2885 2890 2895
Leu Glu Leu Tyr Ser Val Ala Leu Leu Tyr Ser Gly Leu Leu Glu Thr
2900 2905 2910
His Arg Gly Leu Tyr Ile Leu Glu Ala Ser Asn Pro His Glu Ser Glu
2915 2920 2925
Arg Leu Tyr Ser Thr His Arg Ile Leu Glu Thr His Arg Pro His Glu
2930 2935 2940
Gly Leu Asn Met Glu Thr Ala Ser Asn Leu Tyr Ser Ile Leu Glu Pro
2945 2950 2955 2960
Arg Ala Ser Asn Thr His Arg Gly Leu Tyr Leu Glu Ile Leu Glu Thr
2965 2970 2975
His Arg Ser Glu Arg Ala Ser Pro Ser Glu Arg Ala Ser Pro Ala Ser
2980 2985 2990
Asn Ile Leu Glu Ala Ser Asn Met Glu Thr Thr Arg Pro Ile Leu Glu
2995 3000 3005
Ala Arg Gly Ala Ser Pro Pro His Glu Thr Tyr Arg Ile Leu Glu Pro
3010 3015 3020
His Glu Ala Leu Ala Leu Tyr Ser Gly Leu Leu Glu Ala Ser Pro Ala
3025 3030 3035 3040
Ser Pro Leu Tyr Ser Ala Ser Pro Ile Leu Glu Ala Ser Asn Ile Leu
3045 3050 3055
Glu Leu Glu Pro His Glu Ala Ser Asn Ser Glu Arg Leu Glu Gly Leu
3060 3065 3070
Asn Thr Tyr Arg Thr His Arg Ala Ser Asn Val Ala Leu Val Ala Leu
3075 3080 3085
Leu Tyr Ser Ala Ser Pro Thr Tyr Arg Thr Arg Pro Gly Leu Tyr Ala
3090 3095 3100
Ser Asn Ala Ser Pro Leu Glu Ala Arg Gly Thr Tyr Arg Ala Ser Pro
3105 3110 3115 3120
Leu Tyr Ser Gly Leu Thr Tyr Arg Thr Tyr Arg Met Glu Thr Ile Leu
3125 3130 3135
Glu Ala Ser Asn Val Ala Leu Ala Ser Asn Thr Tyr Arg Met Glu Thr
3140 3145 3150
Ala Ser Asn Ala Arg Gly Thr Tyr Arg Met Glu Thr Ser Glu Arg Leu
3155 3160 3165
Tyr Ser Leu Tyr Ser Gly Leu Tyr Ala Ser Asn Gly Leu Tyr Ile Leu
3170 3175 3180
Glu Val Ala Leu Pro His Glu Ala Ser Asn Thr His Arg Ala Arg Gly
3185 3190 3195 3200
Leu Tyr Ser Ala Ser Asn Ala Ser Asn Ala Ser Asn Ala Ser Pro Pro
3205 3210 3215
His Glu Ala Ser Asn Gly Leu Gly Leu Tyr Thr Tyr Arg Leu Tyr Ser
3220 3225 3230
Ile Leu Glu Ile Leu Glu Ile Leu Glu Leu Tyr Ser Ala Arg Gly Ile
3235 3240 3245
Leu Glu Ala Arg Gly Gly Leu Tyr Ala Ser Asn Thr His Arg Ala Ser
3250 3255 3260
Asn Ala Ser Pro Thr His Arg Ala Arg Gly Val Ala Leu Ala Arg Gly
3265 3270 3275 3280
Gly Leu Tyr Gly Leu Ala Ser Asn Val Ala Leu Leu Glu Thr Tyr Arg
3285 3290 3295
Pro His Glu Ala Ser Asn Thr His Arg Thr His Arg Ile Leu Glu Ala
3300 3305 3310
Ser Pro Ala Ser Asn Leu Tyr Ser Gly Leu Asn Thr Tyr Arg Ser Glu
3315 3320 3325
Arg Leu Glu Gly Leu Tyr Met Glu Thr Thr Tyr Arg Leu Tyr Ser Pro
3330 3335 3340
Arg Ser Glu Arg Ala Arg Gly Ala Ser Asn Leu Glu Gly Leu Tyr Thr
3345 3350 3355 3360
His Arg Ala Ser Pro Leu Glu Val Ala Leu Pro Arg Leu Glu Gly Leu
3365 3370 3375
Tyr Ala Leu Ala Leu Glu Ala Ser Pro Gly Leu Asn Pro Arg Met Glu
3380 3385 3390
Thr Ala Ser Pro Gly Leu Ile Leu Glu Ala Arg Gly Leu Tyr Ser Thr
3395 3400 3405
Tyr Arg Gly Leu Tyr Ser Glu Arg Pro His Glu Ile Leu Glu Ile Leu
3410 3415 3420
Glu Gly Leu Asn Pro Arg Cys Tyr Ser Ala Ser Asn Thr His Arg Pro
3425 3430 3435 3440
His Glu Ala Ser Pro Thr Tyr Arg Thr Tyr Arg Ala Leu Ala Ser Glu
3445 3450 3455
Arg Gly Leu Asn Leu Glu Pro His Glu Leu Glu Ser Glu Arg Ser Glu
3460 3465 3470
Arg Ala Ser Asn Ala Leu Ala Thr His Arg Thr His Arg Ala Ser Asn
3475 3480 3485
Ala Arg Gly Leu Glu Gly Leu Tyr Ile Leu Glu Leu Glu Ser Glu Arg
3490 3495 3500
Ile Leu Glu Gly Leu Tyr Ser Glu Arg Thr Tyr Arg Ser Glu Arg Pro
3505 3510 3515 3520
His Glu Leu Tyr Ser Leu Glu Gly Leu Tyr Ala Ser Pro Ala Ser Pro
3525 3530 3535
Thr Tyr Arg Thr Arg Pro Pro His Glu Ala Ser Asn His Ile Ser Gly
3540 3545 3550
Leu Thr Tyr Arg Leu Glu Ile Leu Glu Pro Arg Val Ala Leu Ile Leu
3555 3560 3565
Glu Leu Tyr Ser Ile Leu Glu Gly Leu His Ile Ser Thr Tyr Arg Ala
3570 3575 3580
Leu Ala Ser Glu Arg Leu Glu Leu Glu Gly Leu Ser Glu Arg Thr His
3585 3590 3595 3600
Arg Ser Glu Arg Thr His Arg His Ile Ser Thr Arg Pro Val Ala Leu
3605 3610 3615
Pro His Glu Val Ala Leu Pro Arg Ala Leu Ala Ser Glu Arg Gly Leu
3620 3625 3630
<210> 9
<211> 3756
<212> DNA
<213> Clostridium botulinum
<400> 9
atgccaaaaa ttaatagttt taattataat gatcctgtta atgatagaac aattttatat 60
attaaaccag gcggttgtca agaattttat aaatcattta atattatgaa aaatatttgg 120
ataattccag agagaaatgt aattggtaca accccccaag attttcatcc gcctacttca 180
ttaaaaaatg gagatagtag ttattatgac cctaattatt tacaaagtga tgaagaaaag 240
gatagatttt taaaaatagt cacaaaaata tttaatagaa taaataataa tctttcagga 300
gggattttat tagaagaact gtcaaaagct aatccatatt tagggaatga taatactcca 360
gataatcaat tccatattgg tgatgcatca gcagttgaga ttaaattctc aaatggtagc 420
caagacatac tattacctaa tgttattata atgggagcag agcctgattt atttgaaact 480
aacagttcca atatttctct aagaaataat tatatgccaa gcaatcaccg ttttggatca 540
atagctatag taacattctc acctgaatat tcttttagat ttaatgataa ttgtatgaat 600
gaatttattc aagatcctgc tcttacatta atgcatgaat taatacattc attacatgga 660
ctatatgggg ctaaagggat tactacaaag tatactataa cacaaaaaca aaatccccta 720
ataacaaata taagaggtac aaatattgaa gaattcttaa cttttggagg tactgattta 780
aacattatta ctagtgctca gtccaatgat atctatacta atcttctagc tgattataaa 840
aaaatagcgt ctaaacttag caaagtacaa gtatctaatc cactacttaa tccttataaa 900
gatgtttttg aagcaaagta tggattagat aaagatgcta gcggaattta ttcggtaaat 960
ataaacaaat ttaatgatat ttttaaaaaa ttatacagct ttacggaatt tgatttacga 1020
actaaatttc aagttaaatg taggcaaact tatattggac agtataaata cttcaaactt 1080
tcaaacttgt taaatgattc tatttataat atatcagaag gctataatat aaataattta 1140
aaggtaaatt ttagaggaca gaatgcaaat ttaaatccta gaattattac accaattaca 1200
ggtagaggac tagtaaaaaa aatcattaga ttttgtaaaa atattgtttc tgtaaaaggc 1260
ataaggaaat caatatgtat cgaaataaat aatggtgagt tattttttgt ggcttccgag 1320
aatagttata atgatgataa tataaatact cctaaagaaa ttgacgatac agtaacttca 1380
aataataatt atgaaaatga tttagatcag gttattttaa attttaatag tgaatcagca 1440
cctggacttt cagatgaaaa attaaattta actatccaaa atgatgctta tataccaaaa 1500
tatgattcta atggaacaag tgatatagaa caacatgatg ttaatgaact taatgtattt 1560
ttctatttag atgcacagaa agtgcccgaa ggtgaaaata atgtcaatct cacctcttca 1620
attgatacag cattattaga acaacctaaa atatatacat ttttttcatc agaatttatt 1680
aataatgtca ataaacctgt gcaagcagca ttatttgtaa gctggataca acaagtgtta 1740
gtagatttta ctactgaagc taaccaaaaa agtactgttg ataaaattgc agatatttct 1800
atagttgttc catatatagg tcttgcttta aatataggaa atgaagcaca aaaaggaaat 1860
tttaaagatg cacttgaatt attaggagca ggtattttat tagaatttga acccgagctt 1920
ttaattccta caattttagt attcacgata aaatcttttt taggttcatc tgataataaa 1980
aataaagtta ttaaagcaat aaataatgca ttgaaagaaa gagatgaaaa atggaaagaa 2040
gtatatagtt ttatagtatc gaattggatg actaaaatta atacacaatt taataaaaga 2100
aaagaacaaa tgtatcaagc tttacaaaat caagtaaatg caattaaaac aataatagaa 2160
tctaagtata atagttatac tttagaggaa aaaaatgagc ttacaaataa atatgatatt 2220
aagcaaatag aaaatgaact taatcaaaag gtttctatag caatgaataa tatagacagg 2280
ttcttaactg aaagttctat atcctattta atgaaaataa taaatgaagt aaaaattaat 2340
aaattaagag aatatgatga gaatgtcaaa acgtatttat tgaattatat tatacaacat 2400
ggatcaatct tgggagagag tcagcaagaa ctaaattcta tggtaactga taccctaaat 2460
aatagtattc cttttaagct ttcttcttat acagatgata aaattttaat ttcatatttt 2520
aataaattct ttaagagaat taaaagtagt tcagttttaa atatgagata taaaaatgat 2580
aaatacgtag atacttcagg atatgattca aatataaata ttaatggaga tgtatataaa 2640
tatccaacta ataaaaatca atttggaata tataatgata aacttagtga agttaatata 2700
tctcaaaatg attacattat atatgataat aaatataaaa attttagtat tagtttttgg 2760
gtaagaattc ctaactatga taataagata gtaaatgtta ataatgaata cactataata 2820
aattgtatga gagataataa ttcaggatgg aaagtatctc ttaatcataa tgaaataatt 2880
tggacattcg aagataatcg aggaattaat caaaaattag catttaacta tggtaacgca 2940
aatggtattt ctgattatat aaataagtgg atttttgtaa ctataactaa tgatagatta 3000
ggagattcta aactttatat taatggaaat ttaatagatc aaaaatcaat tttaaattta 3060
ggtaatattc atgttagtga caatatatta tttaaaatag ttaattgtag ttatacaaga 3120
tatattggta ttagatattt taatattttt gataaagaat tagatgaaac agaaattcaa 3180
actttatata gcaatgaacc taatacaaat attttgaagg atttttgggg aaattatttg 3240
ctttatgaca aagaatacta tttattaaat gtgttaaaac caaataactt tattgatagg 3300
agaaaagatt ctactttaag cattaataat ataagaagca ctattctttt agctaataga 3360
ttatatagtg gaataaaagt taaaatacaa agagttaata atagtagtac taacgataat 3420
cttgttagaa agaatgatca ggtatatatt aattttgtag ccagcaaaac tcacttattt 3480
ccattatatg ctgatacagc taccacaaat aaagagaaaa caataaaaat atcatcatct 3540
ggcaatagat ttaatcaagt agtagttatg aattcagtag gaaattgtac aatgaatttt 3600
aaaaataata atggaaataa tattgggttg ttaggtttca aggcagatac tgtcgttgct 3660
agtacttggt attatacaca tatgagagat catacaaaca gcaatggatg tttttggaac 3720
tttatttctg aagaacatgg atggcaagaa aaataa 3756
<210> 10
<211> 3552
<212> PRT
<213> Clostridium botulinum
<400> 10
Met Glu Thr Pro Arg Leu Tyr Ser Ile Leu Glu Ala Ser Asn Ser Glu
1 5 10 15
Arg Pro His Glu Ala Ser Asn Thr Tyr Arg Ala Ser Asn Ala Ser Pro
20 25 30
Pro Arg Val Ala Leu Ala Ser Asn Ala Ser Pro Ala Arg Gly Thr His
35 40 45
Arg Ile Leu Glu Leu Glu Thr Tyr Arg Ile Leu Glu Leu Tyr Ser Pro
50 55 60
Arg Gly Leu Tyr Gly Leu Tyr Cys Tyr Ser Gly Leu Asn Gly Leu Pro
65 70 75 80
His Glu Thr Tyr Arg Leu Tyr Ser Ser Glu Arg Pro His Glu Ala Ser
85 90 95
Asn Ile Leu Glu Met Glu Thr Leu Tyr Ser Ala Ser Asn Ile Leu Glu
100 105 110
Thr Arg Pro Ile Leu Glu Ile Leu Glu Pro Arg Gly Leu Ala Arg Gly
115 120 125
Ala Ser Asn Val Ala Leu Ile Leu Glu Gly Leu Tyr Thr His Arg Thr
130 135 140
His Arg Pro Arg Gly Leu Asn Ala Ser Pro Pro His Glu His Ile Ser
145 150 155 160
Pro Arg Pro Arg Thr His Arg Ser Glu Arg Leu Glu Leu Tyr Ser Ala
165 170 175
Ser Asn Gly Leu Tyr Ala Ser Pro Ser Glu Arg Ser Glu Arg Thr Tyr
180 185 190
Arg Thr Tyr Arg Ala Ser Pro Pro Arg Ala Ser Asn Thr Tyr Arg Leu
195 200 205
Glu Gly Leu Asn Ser Glu Arg Ala Ser Pro Gly Leu Gly Leu Leu Tyr
210 215 220
Ser Ala Ser Pro Ala Arg Gly Pro His Glu Leu Glu Leu Tyr Ser Ile
225 230 235 240
Leu Glu Val Ala Leu Thr His Arg Leu Tyr Ser Ile Leu Glu Pro His
245 250 255
Glu Ala Ser Asn Ala Arg Gly Ile Leu Glu Ala Ser Asn Ala Ser Asn
260 265 270
Ala Ser Asn Leu Glu Ser Glu Arg Gly Leu Tyr Gly Leu Tyr Ile Leu
275 280 285
Glu Leu Glu Leu Glu Gly Leu Gly Leu Leu Glu Ser Glu Arg Leu Tyr
290 295 300
Ser Ala Leu Ala Ala Ser Asn Pro Arg Thr Tyr Arg Leu Glu Gly Leu
305 310 315 320
Tyr Ala Ser Asn Ala Ser Pro Ala Ser Asn Thr His Arg Pro Arg Ala
325 330 335
Ser Pro Ala Ser Asn Gly Leu Asn Pro His Glu His Ile Ser Ile Leu
340 345 350
Glu Gly Leu Tyr Ala Ser Pro Ala Leu Ala Ser Glu Arg Ala Leu Ala
355 360 365
Val Ala Leu Gly Leu Ile Leu Glu Leu Tyr Ser Pro His Glu Ser Glu
370 375 380
Arg Ala Ser Asn Gly Leu Tyr Ser Glu Arg Gly Leu Asn Ala Ser Pro
385 390 395 400
Ile Leu Glu Leu Glu Leu Glu Pro Arg Ala Ser Asn Val Ala Leu Ile
405 410 415
Leu Glu Ile Leu Glu Met Glu Thr Gly Leu Tyr Ala Leu Ala Gly Leu
420 425 430
Pro Arg Ala Ser Pro Leu Glu Pro His Glu Gly Leu Thr His Arg Ala
435 440 445
Ser Asn Ser Glu Arg Ser Glu Arg Ala Ser Asn Ile Leu Glu Ser Glu
450 455 460
Arg Leu Glu Ala Arg Gly Ala Ser Asn Ala Ser Asn Thr Tyr Arg Met
465 470 475 480
Glu Thr Pro Arg Ser Glu Arg Ala Ser Asn His Ile Ser Ala Arg Gly
485 490 495
Pro His Glu Gly Leu Tyr Ser Glu Arg Ile Leu Glu Ala Leu Ala Ile
500 505 510
Leu Glu Val Ala Leu Thr His Arg Pro His Glu Ser Glu Arg Pro Arg
515 520 525
Gly Leu Thr Tyr Arg Ser Glu Arg Pro His Glu Ala Arg Gly Pro His
530 535 540
Glu Ala Ser Asn Ala Ser Pro Ala Ser Asn Cys Tyr Ser Met Glu Thr
545 550 555 560
Ala Ser Asn Gly Leu Pro His Glu Ile Leu Glu Gly Leu Asn Ala Ser
565 570 575
Pro Pro Arg Ala Leu Ala Leu Glu Thr His Arg Leu Glu Met Glu Thr
580 585 590
His Ile Ser Gly Leu Leu Glu Ile Leu Glu His Ile Ser Ser Glu Arg
595 600 605
Leu Glu His Ile Ser Gly Leu Tyr Leu Glu Thr Tyr Arg Gly Leu Tyr
610 615 620
Ala Leu Ala Leu Tyr Ser Gly Leu Tyr Ile Leu Glu Thr His Arg Thr
625 630 635 640
His Arg Leu Tyr Ser Thr Tyr Arg Thr His Arg Ile Leu Glu Thr His
645 650 655
Arg Gly Leu Asn Leu Tyr Ser Gly Leu Asn Ala Ser Asn Pro Arg Leu
660 665 670
Glu Ile Leu Glu Thr His Arg Ala Ser Asn Ile Leu Glu Ala Arg Gly
675 680 685
Gly Leu Tyr Thr His Arg Ala Ser Asn Ile Leu Glu Gly Leu Gly Leu
690 695 700
Pro His Glu Leu Glu Thr His Arg Pro His Glu Gly Leu Tyr Gly Leu
705 710 715 720
Tyr Thr His Arg Ala Ser Pro Leu Glu Ala Ser Asn Ile Leu Glu Ile
725 730 735
Leu Glu Thr His Arg Ser Glu Arg Ala Leu Ala Gly Leu Asn Ser Glu
740 745 750
Arg Ala Ser Asn Ala Ser Pro Ile Leu Glu Thr Tyr Arg Thr His Arg
755 760 765
Ala Ser Asn Leu Glu Leu Glu Ala Leu Ala Ala Ser Pro Thr Tyr Arg
770 775 780
Leu Tyr Ser Leu Tyr Ser Ile Leu Glu Ala Leu Ala Ser Glu Arg Leu
785 790 795 800
Tyr Ser Leu Glu Ser Glu Arg Leu Tyr Ser Val Ala Leu Gly Leu Asn
805 810 815
Val Ala Leu Ser Glu Arg Ala Ser Asn Pro Arg Leu Glu Leu Glu Ala
820 825 830
Ser Asn Pro Arg Thr Tyr Arg Leu Tyr Ser Ala Ser Pro Val Ala Leu
835 840 845
Pro His Glu Gly Leu Ala Leu Ala Leu Tyr Ser Thr Tyr Arg Gly Leu
850 855 860
Tyr Leu Glu Ala Ser Pro Leu Tyr Ser Ala Ser Pro Ala Leu Ala Ser
865 870 875 880
Glu Arg Gly Leu Tyr Ile Leu Glu Thr Tyr Arg Ser Glu Arg Val Ala
885 890 895
Leu Ala Ser Asn Ile Leu Glu Ala Ser Asn Leu Tyr Ser Pro His Glu
900 905 910
Ala Ser Asn Ala Ser Pro Ile Leu Glu Pro His Glu Leu Tyr Ser Leu
915 920 925
Tyr Ser Leu Glu Thr Tyr Arg Ser Glu Arg Pro His Glu Thr His Arg
930 935 940
Gly Leu Pro His Glu Ala Ser Pro Leu Glu Ala Arg Gly Thr His Arg
945 950 955 960
Leu Tyr Ser Pro His Glu Gly Leu Asn Val Ala Leu Leu Tyr Ser Cys
965 970 975
Tyr Ser Ala Arg Gly Gly Leu Asn Thr His Arg Thr Tyr Arg Ile Leu
980 985 990
Glu Gly Leu Tyr Gly Leu Asn Thr Tyr Arg Leu Tyr Ser Thr Tyr Arg
995 1000 1005
Pro His Glu Leu Tyr Ser Leu Glu Ser Glu Arg Ala Ser Asn Leu Glu
1010 1015 1020
Leu Glu Ala Ser Asn Ala Ser Pro Ser Glu Arg Ile Leu Glu Thr Tyr
1025 1030 1035 1040
Arg Ala Ser Asn Ile Leu Glu Ser Glu Arg Gly Leu Gly Leu Tyr Thr
1045 1050 1055
Tyr Arg Ala Ser Asn Ile Leu Glu Ala Ser Asn Ala Ser Asn Leu Glu
1060 1065 1070
Leu Tyr Ser Val Ala Leu Ala Ser Asn Pro His Glu Ala Arg Gly Gly
1075 1080 1085
Leu Tyr Gly Leu Asn Ala Ser Asn Ala Leu Ala Ala Ser Asn Leu Glu
1090 1095 1100
Ala Ser Asn Pro Arg Ala Arg Gly Ile Leu Glu Ile Leu Glu Thr His
1105 1110 1115 1120
Arg Pro Arg Ile Leu Glu Thr His Arg Gly Leu Tyr Ala Arg Gly Gly
1125 1130 1135
Leu Tyr Leu Glu Val Ala Leu Leu Tyr Ser Leu Tyr Ser Ile Leu Glu
1140 1145 1150
Ile Leu Glu Ala Arg Gly Pro His Glu Cys Tyr Ser Leu Tyr Ser Ala
1155 1160 1165
Ser Asn Ile Leu Glu Val Ala Leu Ser Glu Arg Val Ala Leu Leu Tyr
1170 1175 1180
Ser Gly Leu Tyr Ile Leu Glu Ala Arg Gly Leu Tyr Ser Ser Glu Arg
1185 1190 1195 1200
Ile Leu Glu Cys Tyr Ser Ile Leu Glu Gly Leu Ile Leu Glu Ala Ser
1205 1210 1215
Asn Ala Ser Asn Gly Leu Tyr Gly Leu Leu Glu Pro His Glu Pro His
1220 1225 1230
Glu Val Ala Leu Ala Leu Ala Ser Glu Arg Gly Leu Ala Ser Asn Ser
1235 1240 1245
Glu Arg Thr Tyr Arg Ala Ser Asn Ala Ser Pro Ala Ser Pro Ala Ser
1250 1255 1260
Asn Ile Leu Glu Ala Ser Asn Thr His Arg Pro Arg Leu Tyr Ser Gly
1265 1270 1275 1280
Leu Ile Leu Glu Ala Ser Pro Ala Ser Pro Thr His Arg Val Ala Leu
1285 1290 1295
Thr His Arg Ser Glu Arg Ala Ser Asn Ala Ser Asn Ala Ser Asn Thr
1300 1305 1310
Tyr Arg Gly Leu Ala Ser Asn Ala Ser Pro Leu Glu Ala Ser Pro Gly
1315 1320 1325
Leu Asn Val Ala Leu Ile Leu Glu Leu Glu Ala Ser Asn Pro His Glu
1330 1335 1340
Ala Ser Asn Ser Glu Arg Gly Leu Ser Glu Arg Ala Leu Ala Pro Arg
1345 1350 1355 1360
Gly Leu Tyr Leu Glu Ser Glu Arg Ala Ser Pro Gly Leu Leu Tyr Ser
1365 1370 1375
Leu Glu Ala Ser Asn Leu Glu Thr His Arg Ile Leu Glu Gly Leu Asn
1380 1385 1390
Ala Ser Asn Ala Ser Pro Ala Leu Ala Thr Tyr Arg Ile Leu Glu Pro
1395 1400 1405
Arg Leu Tyr Ser Thr Tyr Arg Ala Ser Pro Ser Glu Arg Ala Ser Asn
1410 1415 1420
Gly Leu Tyr Thr His Arg Ser Glu Arg Ala Ser Pro Ile Leu Glu Gly
1425 1430 1435 1440
Leu Gly Leu Asn His Ile Ser Ala Ser Pro Val Ala Leu Ala Ser Asn
1445 1450 1455
Gly Leu Leu Glu Ala Ser Asn Val Ala Leu Pro His Glu Pro His Glu
1460 1465 1470
Thr Tyr Arg Leu Glu Ala Ser Pro Ala Leu Ala Gly Leu Asn Leu Tyr
1475 1480 1485
Ser Val Ala Leu Pro Arg Gly Leu Gly Leu Tyr Gly Leu Ala Ser Asn
1490 1495 1500
Ala Ser Asn Val Ala Leu Ala Ser Asn Leu Glu Thr His Arg Ser Glu
1505 1510 1515 1520
Arg Ser Glu Arg Ile Leu Glu Ala Ser Pro Thr His Arg Ala Leu Ala
1525 1530 1535
Leu Glu Leu Glu Gly Leu Gly Leu Asn Pro Arg Leu Tyr Ser Ile Leu
1540 1545 1550
Glu Thr Tyr Arg Thr His Arg Pro His Glu Pro His Glu Ser Glu Arg
1555 1560 1565
Ser Glu Arg Gly Leu Pro His Glu Ile Leu Glu Ala Ser Asn Ala Ser
1570 1575 1580
Asn Val Ala Leu Ala Ser Asn Leu Tyr Ser Pro Arg Val Ala Leu Gly
1585 1590 1595 1600
Leu Asn Ala Leu Ala Ala Leu Ala Leu Glu Pro His Glu Val Ala Leu
1605 1610 1615
Ser Glu Arg Thr Arg Pro Ile Leu Glu Gly Leu Asn Gly Leu Asn Val
1620 1625 1630
Ala Leu Leu Glu Val Ala Leu Ala Ser Pro Pro His Glu Thr His Arg
1635 1640 1645
Thr His Arg Gly Leu Ala Leu Ala Ala Ser Asn Gly Leu Asn Leu Tyr
1650 1655 1660
Ser Ser Glu Arg Thr His Arg Val Ala Leu Ala Ser Pro Leu Tyr Ser
1665 1670 1675 1680
Ile Leu Glu Ala Leu Ala Ala Ser Pro Ile Leu Glu Ser Glu Arg Ile
1685 1690 1695
Leu Glu Val Ala Leu Val Ala Leu Pro Arg Thr Tyr Arg Ile Leu Glu
1700 1705 1710
Gly Leu Tyr Leu Glu Ala Leu Ala Leu Glu Ala Ser Asn Ile Leu Glu
1715 1720 1725
Gly Leu Tyr Ala Ser Asn Gly Leu Ala Leu Ala Gly Leu Asn Leu Tyr
1730 1735 1740
Ser Gly Leu Tyr Ala Ser Asn Pro His Glu Leu Tyr Ser Ala Ser Pro
1745 1750 1755 1760
Ala Leu Ala Leu Glu Gly Leu Leu Glu Leu Glu Gly Leu Tyr Ala Leu
1765 1770 1775
Ala Gly Leu Tyr Ile Leu Glu Leu Glu Leu Glu Gly Leu Pro His Glu
1780 1785 1790
Gly Leu Pro Arg Gly Leu Leu Glu Leu Glu Ile Leu Glu Pro Arg Thr
1795 1800 1805
His Arg Ile Leu Glu Leu Glu Val Ala Leu Pro His Glu Thr His Arg
1810 1815 1820
Ile Leu Glu Leu Tyr Ser Ser Glu Arg Pro His Glu Leu Glu Gly Leu
1825 1830 1835 1840
Tyr Ser Glu Arg Ser Glu Arg Ala Ser Pro Ala Ser Asn Leu Tyr Ser
1845 1850 1855
Ala Ser Asn Leu Tyr Ser Val Ala Leu Ile Leu Glu Leu Tyr Ser Ala
1860 1865 1870
Leu Ala Ile Leu Glu Ala Ser Asn Ala Ser Asn Ala Leu Ala Leu Glu
1875 1880 1885
Leu Tyr Ser Gly Leu Ala Arg Gly Ala Ser Pro Gly Leu Leu Tyr Ser
1890 1895 1900
Thr Arg Pro Leu Tyr Ser Gly Leu Val Ala Leu Thr Tyr Arg Ser Glu
1905 1910 1915 1920
Arg Pro His Glu Ile Leu Glu Val Ala Leu Ser Glu Arg Ala Ser Asn
1925 1930 1935
Thr Arg Pro Met Glu Thr Thr His Arg Leu Tyr Ser Ile Leu Glu Ala
1940 1945 1950
Ser Asn Thr His Arg Gly Leu Asn Pro His Glu Ala Ser Asn Leu Tyr
1955 1960 1965
Ser Ala Arg Gly Leu Tyr Ser Gly Leu Gly Leu Asn Met Glu Thr Thr
1970 1975 1980
Tyr Arg Gly Leu Asn Ala Leu Ala Leu Glu Gly Leu Asn Ala Ser Asn
1985 1990 1995 2000
Gly Leu Asn Val Ala Leu Ala Ser Asn Ala Leu Ala Ile Leu Glu Leu
2005 2010 2015
Tyr Ser Thr His Arg Ile Leu Glu Ile Leu Glu Gly Leu Ser Glu Arg
2020 2025 2030
Leu Tyr Ser Thr Tyr Arg Ala Ser Asn Ser Glu Arg Thr Tyr Arg Thr
2035 2040 2045
His Arg Leu Glu Gly Leu Gly Leu Leu Tyr Ser Ala Ser Asn Gly Leu
2050 2055 2060
Leu Glu Thr His Arg Ala Ser Asn Leu Tyr Ser Thr Tyr Arg Ala Ser
2065 2070 2075 2080
Pro Ile Leu Glu Leu Tyr Ser Gly Leu Asn Ile Leu Glu Gly Leu Ala
2085 2090 2095
Ser Asn Gly Leu Leu Glu Ala Ser Asn Gly Leu Asn Leu Tyr Ser Val
2100 2105 2110
Ala Leu Ser Glu Arg Ile Leu Glu Ala Leu Ala Met Glu Thr Ala Ser
2115 2120 2125
Asn Ala Ser Asn Ile Leu Glu Ala Ser Pro Ala Arg Gly Pro His Glu
2130 2135 2140
Leu Glu Thr His Arg Gly Leu Ser Glu Arg Ser Glu Arg Ile Leu Glu
2145 2150 2155 2160
Ser Glu Arg Thr Tyr Arg Leu Glu Met Glu Thr Leu Tyr Ser Ile Leu
2165 2170 2175
Glu Ile Leu Glu Ala Ser Asn Gly Leu Val Ala Leu Leu Tyr Ser Ile
2180 2185 2190
Leu Glu Ala Ser Asn Leu Tyr Ser Leu Glu Ala Arg Gly Gly Leu Thr
2195 2200 2205
Tyr Arg Ala Ser Pro Gly Leu Ala Ser Asn Val Ala Leu Leu Tyr Ser
2210 2215 2220
Thr His Arg Thr Tyr Arg Leu Glu Leu Glu Ala Ser Asn Thr Tyr Arg
2225 2230 2235 2240
Ile Leu Glu Ile Leu Glu Gly Leu Asn His Ile Ser Gly Leu Tyr Ser
2245 2250 2255
Glu Arg Ile Leu Glu Leu Glu Gly Leu Tyr Gly Leu Ser Glu Arg Gly
2260 2265 2270
Leu Asn Gly Leu Asn Gly Leu Leu Glu Ala Ser Asn Ser Glu Arg Met
2275 2280 2285
Glu Thr Val Ala Leu Thr His Arg Ala Ser Pro Thr His Arg Leu Glu
2290 2295 2300
Ala Ser Asn Ala Ser Asn Ser Glu Arg Ile Leu Glu Pro Arg Pro His
2305 2310 2315 2320
Glu Leu Tyr Ser Leu Glu Ser Glu Arg Ser Glu Arg Thr Tyr Arg Thr
2325 2330 2335
His Arg Ala Ser Pro Ala Ser Pro Leu Tyr Ser Ile Leu Glu Leu Glu
2340 2345 2350
Ile Leu Glu Ser Glu Arg Thr Tyr Arg Pro His Glu Ala Ser Asn Leu
2355 2360 2365
Tyr Ser Pro His Glu Pro His Glu Leu Tyr Ser Ala Arg Gly Ile Leu
2370 2375 2380
Glu Leu Tyr Ser Ser Glu Arg Ser Glu Arg Ser Glu Arg Val Ala Leu
2385 2390 2395 2400
Leu Glu Ala Ser Asn Met Glu Thr Ala Arg Gly Thr Tyr Arg Leu Tyr
2405 2410 2415
Ser Ala Ser Asn Ala Ser Pro Leu Tyr Ser Thr Tyr Arg Val Ala Leu
2420 2425 2430
Ala Ser Pro Thr His Arg Ser Glu Arg Gly Leu Tyr Thr Tyr Arg Ala
2435 2440 2445
Ser Pro Ser Glu Arg Ala Ser Asn Ile Leu Glu Ala Ser Asn Ile Leu
2450 2455 2460
Glu Ala Ser Asn Gly Leu Tyr Ala Ser Pro Val Ala Leu Thr Tyr Arg
2465 2470 2475 2480
Leu Tyr Ser Thr Tyr Arg Pro Arg Thr His Arg Ala Ser Asn Leu Tyr
2485 2490 2495
Ser Ala Ser Asn Gly Leu Asn Pro His Glu Gly Leu Tyr Ile Leu Glu
2500 2505 2510
Thr Tyr Arg Ala Ser Asn Ala Ser Pro Leu Tyr Ser Leu Glu Ser Glu
2515 2520 2525
Arg Gly Leu Val Ala Leu Ala Ser Asn Ile Leu Glu Ser Glu Arg Gly
2530 2535 2540
Leu Asn Ala Ser Asn Ala Ser Pro Thr Tyr Arg Ile Leu Glu Ile Leu
2545 2550 2555 2560
Glu Thr Tyr Arg Ala Ser Pro Ala Ser Asn Leu Tyr Ser Thr Tyr Arg
2565 2570 2575
Leu Tyr Ser Ala Ser Asn Pro His Glu Ser Glu Arg Ile Leu Glu Ser
2580 2585 2590
Glu Arg Pro His Glu Thr Arg Pro Val Ala Leu Ala Arg Gly Ile Leu
2595 2600 2605
Glu Pro Arg Ala Ser Asn Thr Tyr Arg Ala Ser Pro Ala Ser Asn Leu
2610 2615 2620
Tyr Ser Ile Leu Glu Val Ala Leu Ala Ser Asn Val Ala Leu Ala Ser
2625 2630 2635 2640
Asn Ala Ser Asn Gly Leu Thr Tyr Arg Thr His Arg Ile Leu Glu Ile
2645 2650 2655
Leu Glu Ala Ser Asn Cys Tyr Ser Met Glu Thr Ala Arg Gly Ala Ser
2660 2665 2670
Pro Ala Ser Asn Ala Ser Asn Ser Glu Arg Gly Leu Tyr Thr Arg Pro
2675 2680 2685
Leu Tyr Ser Val Ala Leu Ser Glu Arg Leu Glu Ala Ser Asn His Ile
2690 2695 2700
Ser Ala Ser Asn Gly Leu Ile Leu Glu Ile Leu Glu Thr Arg Pro Thr
2705 2710 2715 2720
His Arg Pro His Glu Gly Leu Ala Ser Pro Ala Ser Asn Ala Arg Gly
2725 2730 2735
Gly Leu Tyr Ile Leu Glu Ala Ser Asn Gly Leu Asn Leu Tyr Ser Leu
2740 2745 2750
Glu Ala Leu Ala Pro His Glu Ala Ser Asn Thr Tyr Arg Gly Leu Tyr
2755 2760 2765
Ala Ser Asn Ala Leu Ala Ala Ser Asn Gly Leu Tyr Ile Leu Glu Ser
2770 2775 2780
Glu Arg Ala Ser Pro Thr Tyr Arg Ile Leu Glu Ala Ser Asn Leu Tyr
2785 2790 2795 2800
Ser Thr Arg Pro Ile Leu Glu Pro His Glu Val Ala Leu Thr His Arg
2805 2810 2815
Ile Leu Glu Thr His Arg Ala Ser Asn Ala Ser Pro Ala Arg Gly Leu
2820 2825 2830
Glu Gly Leu Tyr Ala Ser Pro Ser Glu Arg Leu Tyr Ser Leu Glu Thr
2835 2840 2845
Tyr Arg Ile Leu Glu Ala Ser Asn Gly Leu Tyr Ala Ser Asn Leu Glu
2850 2855 2860
Ile Leu Glu Ala Ser Pro Gly Leu Asn Leu Tyr Ser Ser Glu Arg Ile
2865 2870 2875 2880
Leu Glu Leu Glu Ala Ser Asn Leu Glu Gly Leu Tyr Ala Ser Asn Ile
2885 2890 2895
Leu Glu His Ile Ser Val Ala Leu Ser Glu Arg Ala Ser Pro Ala Ser
2900 2905 2910
Asn Ile Leu Glu Leu Glu Pro His Glu Leu Tyr Ser Ile Leu Glu Val
2915 2920 2925
Ala Leu Ala Ser Asn Cys Tyr Ser Ser Glu Arg Thr Tyr Arg Thr His
2930 2935 2940
Arg Ala Arg Gly Thr Tyr Arg Ile Leu Glu Gly Leu Tyr Ile Leu Glu
2945 2950 2955 2960
Ala Arg Gly Thr Tyr Arg Pro His Glu Ala Ser Asn Ile Leu Glu Pro
2965 2970 2975
His Glu Ala Ser Pro Leu Tyr Ser Gly Leu Leu Glu Ala Ser Pro Gly
2980 2985 2990
Leu Thr His Arg Gly Leu Ile Leu Glu Gly Leu Asn Thr His Arg Leu
2995 3000 3005
Glu Thr Tyr Arg Ser Glu Arg Ala Ser Asn Gly Leu Pro Arg Ala Ser
3010 3015 3020
Asn Thr His Arg Ala Ser Asn Ile Leu Glu Leu Glu Leu Tyr Ser Ala
3025 3030 3035 3040
Ser Pro Pro His Glu Thr Arg Pro Gly Leu Tyr Ala Ser Asn Thr Tyr
3045 3050 3055
Arg Leu Glu Leu Glu Thr Tyr Arg Ala Ser Pro Leu Tyr Ser Gly Leu
3060 3065 3070
Thr Tyr Arg Thr Tyr Arg Leu Glu Leu Glu Ala Ser Asn Val Ala Leu
3075 3080 3085
Leu Glu Leu Tyr Ser Pro Arg Ala Ser Asn Ala Ser Asn Pro His Glu
3090 3095 3100
Ile Leu Glu Ala Ser Pro Ala Arg Gly Ala Arg Gly Leu Tyr Ser Ala
3105 3110 3115 3120
Ser Pro Ser Glu Arg Thr His Arg Leu Glu Ser Glu Arg Ile Leu Glu
3125 3130 3135
Ala Ser Asn Ala Ser Asn Ile Leu Glu Ala Arg Gly Ser Glu Arg Thr
3140 3145 3150
His Arg Ile Leu Glu Leu Glu Leu Glu Ala Leu Ala Ala Ser Asn Ala
3155 3160 3165
Arg Gly Leu Glu Thr Tyr Arg Ser Glu Arg Gly Leu Tyr Ile Leu Glu
3170 3175 3180
Leu Tyr Ser Val Ala Leu Leu Tyr Ser Ile Leu Glu Gly Leu Asn Ala
3185 3190 3195 3200
Arg Gly Val Ala Leu Ala Ser Asn Ala Ser Asn Ser Glu Arg Ser Glu
3205 3210 3215
Arg Thr His Arg Ala Ser Asn Ala Ser Pro Ala Ser Asn Leu Glu Val
3220 3225 3230
Ala Leu Ala Arg Gly Leu Tyr Ser Ala Ser Asn Ala Ser Pro Gly Leu
3235 3240 3245
Asn Val Ala Leu Thr Tyr Arg Ile Leu Glu Ala Ser Asn Pro His Glu
3250 3255 3260
Val Ala Leu Ala Leu Ala Ser Glu Arg Leu Tyr Ser Thr His Arg His
3265 3270 3275 3280
Ile Ser Leu Glu Pro His Glu Pro Arg Leu Glu Thr Tyr Arg Ala Leu
3285 3290 3295
Ala Ala Ser Pro Thr His Arg Ala Leu Ala Thr His Arg Thr His Arg
3300 3305 3310
Ala Ser Asn Leu Tyr Ser Gly Leu Leu Tyr Ser Thr His Arg Ile Leu
3315 3320 3325
Glu Leu Tyr Ser Ile Leu Glu Ser Glu Arg Ser Glu Arg Ser Glu Arg
3330 3335 3340
Gly Leu Tyr Ala Ser Asn Ala Arg Gly Pro His Glu Ala Ser Asn Gly
3345 3350 3355 3360
Leu Asn Val Ala Leu Val Ala Leu Val Ala Leu Met Glu Thr Ala Ser
3365 3370 3375
Asn Ser Glu Arg Val Ala Leu Gly Leu Tyr Ala Ser Asn Cys Tyr Ser
3380 3385 3390
Thr His Arg Met Glu Thr Ala Ser Asn Pro His Glu Leu Tyr Ser Ala
3395 3400 3405
Ser Asn Ala Ser Asn Ala Ser Asn Gly Leu Tyr Ala Ser Asn Ala Ser
3410 3415 3420
Asn Ile Leu Glu Gly Leu Tyr Leu Glu Leu Glu Gly Leu Tyr Pro His
3425 3430 3435 3440
Glu Leu Tyr Ser Ala Leu Ala Ala Ser Pro Thr His Arg Val Ala Leu
3445 3450 3455
Val Ala Leu Ala Leu Ala Ser Glu Arg Thr His Arg Thr Arg Pro Thr
3460 3465 3470
Tyr Arg Thr Tyr Arg Thr His Arg His Ile Ser Met Glu Thr Ala Arg
3475 3480 3485
Gly Ala Ser Pro His Ile Ser Thr His Arg Ala Ser Asn Ser Glu Arg
3490 3495 3500
Ala Ser Asn Gly Leu Tyr Cys Tyr Ser Pro His Glu Thr Arg Pro Ala
3505 3510 3515 3520
Ser Asn Pro His Glu Ile Leu Glu Ser Glu Arg Gly Leu Gly Leu His
3525 3530 3535
Ile Ser Gly Leu Tyr Thr Arg Pro Gly Leu Asn Gly Leu Leu Tyr Ser
3540 3545 3550
<210> 11
<211> 3843
<212> DNA
<213> Clostridium botulinum
<400> 11
atgccagttg taataaatag ttttaattat aatgaccctg ttaatgatga gacaatttta 60
tacatgcaga aaccatatga agaaagaagt agaaaatatt ataaagcttt tgagattatg 120
cctaatgttt ggataatgcc tgagagagat acaataggaa ctaagcctga tgagtttcag 180
gtgccggatt cattaaagaa cggaagtagt gcttattatg atcctaatta tttaaccact 240
gatgctgaaa aagatagata tttaaaaaca atgataaaat tatttaatag aattaatagt 300
aatcctacag ggaaagtttt gttagaagaa gtatcaaatg ctagaccata tttaggagat 360
gatgacacgc taattaatga attccttcca gttaatgtaa ctacaagtgt taatataaaa 420
ttttcaactg atgttgaaag ttcaataata tcgaatcttc ttgtattggg agcaggacct 480
gatatattta aagcttactg tacccccctt gtaaggttta ataagtcaga taaattaatt 540
gaaccaagta atcatggttt tggatcaatt aatatcttga cattttcacc tgagtatgaa 600
catattttta atgatattag tggagggaat cataatagta cagaatcatt tattgcagat 660
cctgcaattt cactagctca tgaattgata catgcactac atggattata cggggctaag 720
gcagttactc ataaagagtc tctagtagca gagcgaggac ctcttatgat agccgaaaag 780
cccataaggc tagaagaatt tttaactttt ggaggtgagg atttaaatat cattcctagt 840
gctatgaagg aaaaaatata taacgatctt ttagctaact atgaaaaaat agctactaga 900
cttagagaag ttaatacggc tcctcctgga tatgatatta atgaatataa agattatttt 960
caatggaagt atggactaga tagaaatgca gatggaagtt atactgtgaa tagaaataaa 1020
tttaatgaaa tttataaaaa attatatagc tttacagaga ttgacttagc aaataaattt 1080
aaagtaaaat gtagaaatac ttattttatt aaatatggat ttgtaaaagt tccaaatttg 1140
ttagatgatg atatttatac tgtatcagag gggtttaata taggtaattt agcagtaaac 1200
aatcgcggac aaaatataaa tttaaatcct aaaattattg attccattcc agataaaggt 1260
ttagtggaaa agattattaa attttgtaag agcattattc ctagaaaagg tacgaagcag 1320
tcaccgtcac tatgcattag agtaaataat agggagttat tttttgtagc ttcagaaagt 1380
agctataatg aaagtgatat taatacacct aaagaaattg acgatacaac aaatctaaat 1440
aataattata gaaataattt agatgaagtt attttagatt ataatagtga gacaatacct 1500
caaatatcaa atcgaacatt aaatacactt gtacaagaca atagttatgt gccaagatat 1560
gattctaatg gaacaagtga aatagaggaa tatgatgttg ttgactttaa tgtatttttc 1620
tatttacatg cacaaaaagt accagaaggt gaaaccaata taagtttaac ttcttcaatt 1680
gatacagcat tattagaaga atccaaagta tatacatttt tttcttcaga gtttatcgat 1740
actatcaata aacctgtaaa tgcagcacta tttatagatt ggataagcaa agtaataaga 1800
gattttacca ctgaagctac acaaaaaagt actgttgata agattgcaga catatcttta 1860
attgtaccct atgtaggtct tgctttgaat atagttattg aggcagaaaa aggaaatttt 1920
gaggaggcat ttgaattatt aggagcgggt attttattag aatttgtgcc agagcttaca 1980
attcctgtaa ttttagtgtt tacgataaaa tcctatatag attcatatga gaataaaaat 2040
aaagcaatta aagcaataaa taattcatta atcgaaagag aagcaaagtg gaaagaaata 2100
tatagttgga tagtatcaaa ttggcttact agaattaata cgcaatttaa taaaagaaaa 2160
gagcaaatgt atcaggcttt acaaaatcaa gtagatgcaa taaaaacagc aatagaatat 2220
aaatataata attatacttc agatgagaaa aatagacttg aatctaaata taatatcaat 2280
aatatagaag aagaattgaa taaaaaagtt tctttagcaa tgaaaaatat agaaagattt 2340
atgacagaaa gttctatatc ttatttaatg aaattaataa atgaagccga agttggtaaa 2400
ttaaaagaat atgataaaca tgttaagagc gatttattag actatattct ctaccataaa 2460
ttaatcttag gagagcagac aaaggaatta attgatttgg tgactagtac tttgaatagt 2520
agtattccat ttgaactttc ttcatatact aatgataaaa ttctaattat atattttaat 2580
agattatata aaaaaattaa agatagttct attttagata tgcgatatga aaataataaa 2640
tttatagata tctctggata tggttcaaat ataagcatta atggaaacgt atatatttat 2700
tcaacaaata gaaatcaatt tggaatatat agtggtaggc ttagtgaagt taatatagct 2760
caaaataatg atattatata caatagtaga tatcaaaatt ttagtattag tttctgggta 2820
accattccta aacactacag acctatgaat cgtaatcggg aatacactat aataaattgt 2880
atggggaata ataattcggg atggaaaata tcacttagaa ctattagaga ttgtgaaata 2940
atttggactt tacaagatac ttccggaaat aaggaaaaat taatttttag gtatgaagaa 3000
cttgctagta tatctgatta tataaataaa tggatttttg taactattac taataataga 3060
ttaggcaatt ctagaattta catcaatgga aatttaatag ttgaaaaatc aatttcgaat 3120
ttaggtgata ttcatgttag tgataatata ttatttaaaa ttgttggttg tgatgatgaa 3180
acgtatgttg gtataagata ttttaaagtt tttaatacgg aattagataa aacagaaatt 3240
gagactttat atagtaatga gccagatcca agtatcttaa aagactattg gggaaattat 3300
ttgctatata ataaaaaata ttatttattc aatttactaa gaaaagataa gtatattact 3360
cggaattcag gcattttaaa tattaatcaa caaagaggtg ttactggagg catatctgtt 3420
tttttgaact ataaattata tgaaggagta gaagttatta taagaaaaaa tgctcctata 3480
gatatatcta atacagataa ttttgttaga aaaaacgatc tagcatacat taatgtagta 3540
gatcatggtg tagaatatcg gttatatgct gatatatcaa ttacaaaatc agagaaaata 3600
ataaaattaa taagaacatc taatccaaac gatagcttag gtcaaattat agttatggat 3660
tcaataggaa ataattgcac aatgaatttt caaaacaatg atgggagcaa tataggatta 3720
ctaggttttc attcagatga tttggttgct agtagttggt attataacca tatacgaaga 3780
aacactagca gtaatggatg cttttggagt tttatttcta aagagcatgg ttggaaagaa 3840
taa 3843
<210> 12
<211> 3604
<212> PRT
<213> Clostridium botulinum
<400> 12
Met Glu Thr Pro Arg Val Ala Leu Val Ala Leu Ile Leu Glu Ala Ser
1 5 10 15
Asn Ser Glu Arg Pro His Glu Ala Ser Asn Thr Tyr Arg Ala Ser Asn
20 25 30
Ala Ser Pro Pro Arg Val Ala Leu Ala Ser Asn Ala Ser Pro Gly Leu
35 40 45
Thr His Arg Ile Leu Glu Leu Glu Thr Tyr Arg Met Glu Thr Gly Leu
50 55 60
Asn Leu Tyr Ser Pro Arg Thr Tyr Arg Gly Leu Gly Leu Ala Arg Gly
65 70 75 80
Ser Glu Arg Ala Arg Gly Leu Tyr Ser Thr Tyr Arg Thr Tyr Arg Leu
85 90 95
Tyr Ser Ala Leu Ala Pro His Glu Gly Leu Ile Leu Glu Met Glu Thr
100 105 110
Pro Arg Ala Ser Asn Val Ala Leu Thr Arg Pro Ile Leu Glu Met Glu
115 120 125
Thr Pro Arg Gly Leu Ala Arg Gly Ala Ser Pro Thr His Arg Ile Leu
130 135 140
Glu Gly Leu Tyr Thr His Arg Leu Tyr Ser Pro Arg Ala Ser Pro Gly
145 150 155 160
Leu Pro His Glu Gly Leu Asn Val Ala Leu Pro Arg Ala Ser Pro Ser
165 170 175
Glu Arg Leu Glu Leu Tyr Ser Ala Ser Asn Gly Leu Tyr Ser Glu Arg
180 185 190
Ser Glu Arg Ala Leu Ala Thr Tyr Arg Thr Tyr Arg Ala Ser Pro Pro
195 200 205
Arg Ala Ser Asn Thr Tyr Arg Leu Glu Thr His Arg Thr His Arg Ala
210 215 220
Ser Pro Ala Leu Ala Gly Leu Leu Tyr Ser Ala Ser Pro Ala Arg Gly
225 230 235 240
Thr Tyr Arg Leu Glu Leu Tyr Ser Thr His Arg Met Glu Thr Ile Leu
245 250 255
Glu Leu Tyr Ser Leu Glu Pro His Glu Ala Ser Asn Ala Arg Gly Ile
260 265 270
Leu Glu Ala Ser Asn Ser Glu Arg Ala Ser Asn Pro Arg Thr His Arg
275 280 285
Gly Leu Tyr Leu Tyr Ser Val Ala Leu Leu Glu Leu Glu Gly Leu Gly
290 295 300
Leu Val Ala Leu Ser Glu Arg Ala Ser Asn Ala Leu Ala Ala Arg Gly
305 310 315 320
Pro Arg Thr Tyr Arg Leu Glu Gly Leu Tyr Ala Ser Pro Ala Ser Pro
325 330 335
Ala Ser Pro Thr His Arg Leu Glu Ile Leu Glu Ala Ser Asn Gly Leu
340 345 350
Pro His Glu Leu Glu Pro Arg Val Ala Leu Ala Ser Asn Val Ala Leu
355 360 365
Thr His Arg Thr His Arg Ser Glu Arg Val Ala Leu Ala Ser Asn Ile
370 375 380
Leu Glu Leu Tyr Ser Pro His Glu Ser Glu Arg Thr His Arg Ala Ser
385 390 395 400
Pro Val Ala Leu Gly Leu Ser Glu Arg Ser Glu Arg Ile Leu Glu Ile
405 410 415
Leu Glu Ser Glu Arg Ala Ser Asn Leu Glu Leu Glu Val Ala Leu Leu
420 425 430
Glu Gly Leu Tyr Ala Leu Ala Gly Leu Tyr Pro Arg Ala Ser Pro Ile
435 440 445
Leu Glu Pro His Glu Leu Tyr Ser Ala Leu Ala Thr Tyr Arg Cys Tyr
450 455 460
Ser Thr His Arg Pro Arg Leu Glu Val Ala Leu Ala Arg Gly Pro His
465 470 475 480
Glu Ala Ser Asn Leu Tyr Ser Ser Glu Arg Ala Ser Pro Leu Tyr Ser
485 490 495
Leu Glu Ile Leu Glu Gly Leu Pro Arg Ser Glu Arg Ala Ser Asn His
500 505 510
Ile Ser Gly Leu Tyr Pro His Glu Gly Leu Tyr Ser Glu Arg Ile Leu
515 520 525
Glu Ala Ser Asn Ile Leu Glu Leu Glu Thr His Arg Pro His Glu Ser
530 535 540
Glu Arg Pro Arg Gly Leu Thr Tyr Arg Gly Leu His Ile Ser Ile Leu
545 550 555 560
Glu Pro His Glu Ala Ser Asn Ala Ser Pro Ile Leu Glu Ser Glu Arg
565 570 575
Gly Leu Tyr Gly Leu Tyr Ala Ser Asn His Ile Ser Ala Ser Asn Ser
580 585 590
Glu Arg Thr His Arg Gly Leu Ser Glu Arg Pro His Glu Ile Leu Glu
595 600 605
Ala Leu Ala Ala Ser Pro Pro Arg Ala Leu Ala Ile Leu Glu Ser Glu
610 615 620
Arg Leu Glu Ala Leu Ala His Ile Ser Gly Leu Leu Glu Ile Leu Glu
625 630 635 640
His Ile Ser Ala Leu Ala Leu Glu His Ile Ser Gly Leu Tyr Leu Glu
645 650 655
Thr Tyr Arg Gly Leu Tyr Ala Leu Ala Leu Tyr Ser Ala Leu Ala Val
660 665 670
Ala Leu Thr His Arg His Ile Ser Leu Tyr Ser Gly Leu Ser Glu Arg
675 680 685
Leu Glu Val Ala Leu Ala Leu Ala Gly Leu Ala Arg Gly Gly Leu Tyr
690 695 700
Pro Arg Leu Glu Met Glu Thr Ile Leu Glu Ala Leu Ala Gly Leu Leu
705 710 715 720
Tyr Ser Pro Arg Ile Leu Glu Ala Arg Gly Leu Glu Gly Leu Gly Leu
725 730 735
Pro His Glu Leu Glu Thr His Arg Pro His Glu Gly Leu Tyr Gly Leu
740 745 750
Tyr Gly Leu Ala Ser Pro Leu Glu Ala Ser Asn Ile Leu Glu Ile Leu
755 760 765
Glu Pro Arg Ser Glu Arg Ala Leu Ala Met Glu Thr Leu Tyr Ser Gly
770 775 780
Leu Leu Tyr Ser Ile Leu Glu Thr Tyr Arg Ala Ser Asn Ala Ser Pro
785 790 795 800
Leu Glu Leu Glu Ala Leu Ala Ala Ser Asn Thr Tyr Arg Gly Leu Leu
805 810 815
Tyr Ser Ile Leu Glu Ala Leu Ala Thr His Arg Ala Arg Gly Leu Glu
820 825 830
Ala Arg Gly Gly Leu Val Ala Leu Ala Ser Asn Thr His Arg Ala Leu
835 840 845
Ala Pro Arg Pro Arg Gly Leu Tyr Thr Tyr Arg Ala Ser Pro Ile Leu
850 855 860
Glu Ala Ser Asn Gly Leu Thr Tyr Arg Leu Tyr Ser Ala Ser Pro Thr
865 870 875 880
Tyr Arg Pro His Glu Gly Leu Asn Thr Arg Pro Leu Tyr Ser Thr Tyr
885 890 895
Arg Gly Leu Tyr Leu Glu Ala Ser Pro Ala Arg Gly Ala Ser Asn Ala
900 905 910
Leu Ala Ala Ser Pro Gly Leu Tyr Ser Glu Arg Thr Tyr Arg Thr His
915 920 925
Arg Val Ala Leu Ala Ser Asn Ala Arg Gly Ala Ser Asn Leu Tyr Ser
930 935 940
Pro His Glu Ala Ser Asn Gly Leu Ile Leu Glu Thr Tyr Arg Leu Tyr
945 950 955 960
Ser Leu Tyr Ser Leu Glu Thr Tyr Arg Ser Glu Arg Pro His Glu Thr
965 970 975
His Arg Gly Leu Ile Leu Glu Ala Ser Pro Leu Glu Ala Leu Ala Ala
980 985 990
Ser Asn Leu Tyr Ser Pro His Glu Leu Tyr Ser Val Ala Leu Leu Tyr
995 1000 1005
Ser Cys Tyr Ser Ala Arg Gly Ala Ser Asn Thr His Arg Thr Tyr Arg
1010 1015 1020
Pro His Glu Ile Leu Glu Leu Tyr Ser Thr Tyr Arg Gly Leu Tyr Pro
1025 1030 1035 1040
His Glu Val Ala Leu Leu Tyr Ser Val Ala Leu Pro Arg Ala Ser Asn
1045 1050 1055
Leu Glu Leu Glu Ala Ser Pro Ala Ser Pro Ala Ser Pro Ile Leu Glu
1060 1065 1070
Thr Tyr Arg Thr His Arg Val Ala Leu Ser Glu Arg Gly Leu Gly Leu
1075 1080 1085
Tyr Pro His Glu Ala Ser Asn Ile Leu Glu Gly Leu Tyr Ala Ser Asn
1090 1095 1100
Leu Glu Ala Leu Ala Val Ala Leu Ala Ser Asn Ala Ser Asn Ala Arg
1105 1110 1115 1120
Gly Gly Leu Tyr Gly Leu Asn Ala Ser Asn Ile Leu Glu Ala Ser Asn
1125 1130 1135
Leu Glu Ala Ser Asn Pro Arg Leu Tyr Ser Ile Leu Glu Ile Leu Glu
1140 1145 1150
Ala Ser Pro Ser Glu Arg Ile Leu Glu Pro Arg Ala Ser Pro Leu Tyr
1155 1160 1165
Ser Gly Leu Tyr Leu Glu Val Ala Leu Gly Leu Leu Tyr Ser Ile Leu
1170 1175 1180
Glu Ile Leu Glu Leu Tyr Ser Pro His Glu Cys Tyr Ser Leu Tyr Ser
1185 1190 1195 1200
Ser Glu Arg Ile Leu Glu Ile Leu Glu Pro Arg Ala Arg Gly Leu Tyr
1205 1210 1215
Ser Gly Leu Tyr Thr His Arg Leu Tyr Ser Gly Leu Asn Ser Glu Arg
1220 1225 1230
Pro Arg Ser Glu Arg Leu Glu Cys Tyr Ser Ile Leu Glu Ala Arg Gly
1235 1240 1245
Val Ala Leu Ala Ser Asn Ala Ser Asn Ala Arg Gly Gly Leu Leu Glu
1250 1255 1260
Pro His Glu Pro His Glu Val Ala Leu Ala Leu Ala Ser Glu Arg Gly
1265 1270 1275 1280
Leu Ser Glu Arg Ser Glu Arg Thr Tyr Arg Ala Ser Asn Gly Leu Ser
1285 1290 1295
Glu Arg Ala Ser Pro Ile Leu Glu Ala Ser Asn Thr His Arg Pro Arg
1300 1305 1310
Leu Tyr Ser Gly Leu Ile Leu Glu Ala Ser Pro Ala Ser Pro Thr His
1315 1320 1325
Arg Thr His Arg Ala Ser Asn Leu Glu Ala Ser Asn Ala Ser Asn Ala
1330 1335 1340
Ser Asn Thr Tyr Arg Ala Arg Gly Ala Ser Asn Ala Ser Asn Leu Glu
1345 1350 1355 1360
Ala Ser Pro Gly Leu Val Ala Leu Ile Leu Glu Leu Glu Ala Ser Pro
1365 1370 1375
Thr Tyr Arg Ala Ser Asn Ser Glu Arg Gly Leu Thr His Arg Ile Leu
1380 1385 1390
Glu Pro Arg Gly Leu Asn Ile Leu Glu Ser Glu Arg Ala Ser Asn Ala
1395 1400 1405
Arg Gly Thr His Arg Leu Glu Ala Ser Asn Thr His Arg Leu Glu Val
1410 1415 1420
Ala Leu Gly Leu Asn Ala Ser Pro Ala Ser Asn Ser Glu Arg Thr Tyr
1425 1430 1435 1440
Arg Val Ala Leu Pro Arg Ala Arg Gly Thr Tyr Arg Ala Ser Pro Ser
1445 1450 1455
Glu Arg Ala Ser Asn Gly Leu Tyr Thr His Arg Ser Glu Arg Gly Leu
1460 1465 1470
Ile Leu Glu Gly Leu Gly Leu Thr Tyr Arg Ala Ser Pro Val Ala Leu
1475 1480 1485
Val Ala Leu Ala Ser Pro Pro His Glu Ala Ser Asn Val Ala Leu Pro
1490 1495 1500
His Glu Pro His Glu Thr Tyr Arg Leu Glu His Ile Ser Ala Leu Ala
1505 1510 1515 1520
Gly Leu Asn Leu Tyr Ser Val Ala Leu Pro Arg Gly Leu Gly Leu Tyr
1525 1530 1535
Gly Leu Thr His Arg Ala Ser Asn Ile Leu Glu Ser Glu Arg Leu Glu
1540 1545 1550
Thr His Arg Ser Glu Arg Ser Glu Arg Ile Leu Glu Ala Ser Pro Thr
1555 1560 1565
His Arg Ala Leu Ala Leu Glu Leu Glu Gly Leu Gly Leu Ser Glu Arg
1570 1575 1580
Leu Tyr Ser Val Ala Leu Thr Tyr Arg Thr His Arg Pro His Glu Pro
1585 1590 1595 1600
His Glu Ser Glu Arg Ser Glu Arg Gly Leu Pro His Glu Ile Leu Glu
1605 1610 1615
Ala Ser Pro Thr His Arg Ile Leu Glu Ala Ser Asn Leu Tyr Ser Pro
1620 1625 1630
Arg Val Ala Leu Ala Ser Asn Ala Leu Ala Ala Leu Ala Leu Glu Pro
1635 1640 1645
His Glu Ile Leu Glu Ala Ser Pro Thr Arg Pro Ile Leu Glu Ser Glu
1650 1655 1660
Arg Leu Tyr Ser Val Ala Leu Ile Leu Glu Ala Arg Gly Ala Ser Pro
1665 1670 1675 1680
Pro His Glu Thr His Arg Thr His Arg Gly Leu Ala Leu Ala Thr His
1685 1690 1695
Arg Gly Leu Asn Leu Tyr Ser Ser Glu Arg Thr His Arg Val Ala Leu
1700 1705 1710
Ala Ser Pro Leu Tyr Ser Ile Leu Glu Ala Leu Ala Ala Ser Pro Ile
1715 1720 1725
Leu Glu Ser Glu Arg Leu Glu Ile Leu Glu Val Ala Leu Pro Arg Thr
1730 1735 1740
Tyr Arg Val Ala Leu Gly Leu Tyr Leu Glu Ala Leu Ala Leu Glu Ala
1745 1750 1755 1760
Ser Asn Ile Leu Glu Val Ala Leu Ile Leu Glu Gly Leu Ala Leu Ala
1765 1770 1775
Gly Leu Leu Tyr Ser Gly Leu Tyr Ala Ser Asn Pro His Glu Gly Leu
1780 1785 1790
Gly Leu Ala Leu Ala Pro His Glu Gly Leu Leu Glu Leu Glu Gly Leu
1795 1800 1805
Tyr Ala Leu Ala Gly Leu Tyr Ile Leu Glu Leu Glu Leu Glu Gly Leu
1810 1815 1820
Pro His Glu Val Ala Leu Pro Arg Gly Leu Leu Glu Thr His Arg Ile
1825 1830 1835 1840
Leu Glu Pro Arg Val Ala Leu Ile Leu Glu Leu Glu Val Ala Leu Pro
1845 1850 1855
His Glu Thr His Arg Ile Leu Glu Leu Tyr Ser Ser Glu Arg Thr Tyr
1860 1865 1870
Arg Ile Leu Glu Ala Ser Pro Ser Glu Arg Thr Tyr Arg Gly Leu Ala
1875 1880 1885
Ser Asn Leu Tyr Ser Ala Ser Asn Leu Tyr Ser Ala Leu Ala Ile Leu
1890 1895 1900
Glu Leu Tyr Ser Ala Leu Ala Ile Leu Glu Ala Ser Asn Ala Ser Asn
1905 1910 1915 1920
Ser Glu Arg Leu Glu Ile Leu Glu Gly Leu Ala Arg Gly Gly Leu Ala
1925 1930 1935
Leu Ala Leu Tyr Ser Thr Arg Pro Leu Tyr Ser Gly Leu Ile Leu Glu
1940 1945 1950
Thr Tyr Arg Ser Glu Arg Thr Arg Pro Ile Leu Glu Val Ala Leu Ser
1955 1960 1965
Glu Arg Ala Ser Asn Thr Arg Pro Leu Glu Thr His Arg Ala Arg Gly
1970 1975 1980
Ile Leu Glu Ala Ser Asn Thr His Arg Gly Leu Asn Pro His Glu Ala
1985 1990 1995 2000
Ser Asn Leu Tyr Ser Ala Arg Gly Leu Tyr Ser Gly Leu Gly Leu Asn
2005 2010 2015
Met Glu Thr Thr Tyr Arg Gly Leu Asn Ala Leu Ala Leu Glu Gly Leu
2020 2025 2030
Asn Ala Ser Asn Gly Leu Asn Val Ala Leu Ala Ser Pro Ala Leu Ala
2035 2040 2045
Ile Leu Glu Leu Tyr Ser Thr His Arg Ala Leu Ala Ile Leu Glu Gly
2050 2055 2060
Leu Thr Tyr Arg Leu Tyr Ser Thr Tyr Arg Ala Ser Asn Ala Ser Asn
2065 2070 2075 2080
Thr Tyr Arg Thr His Arg Ser Glu Arg Ala Ser Pro Gly Leu Leu Tyr
2085 2090 2095
Ser Ala Ser Asn Ala Arg Gly Leu Glu Gly Leu Ser Glu Arg Leu Tyr
2100 2105 2110
Ser Thr Tyr Arg Ala Ser Asn Ile Leu Glu Ala Ser Asn Ala Ser Asn
2115 2120 2125
Ile Leu Glu Gly Leu Gly Leu Gly Leu Leu Glu Ala Ser Asn Leu Tyr
2130 2135 2140
Ser Leu Tyr Ser Val Ala Leu Ser Glu Arg Leu Glu Ala Leu Ala Met
2145 2150 2155 2160
Glu Thr Leu Tyr Ser Ala Ser Asn Ile Leu Glu Gly Leu Ala Arg Gly
2165 2170 2175
Pro His Glu Met Glu Thr Thr His Arg Gly Leu Ser Glu Arg Ser Glu
2180 2185 2190
Arg Ile Leu Glu Ser Glu Arg Thr Tyr Arg Leu Glu Met Glu Thr Leu
2195 2200 2205
Tyr Ser Leu Glu Ile Leu Glu Ala Ser Asn Gly Leu Ala Leu Ala Gly
2210 2215 2220
Leu Val Ala Leu Gly Leu Tyr Leu Tyr Ser Leu Glu Leu Tyr Ser Gly
2225 2230 2235 2240
Leu Thr Tyr Arg Ala Ser Pro Leu Tyr Ser His Ile Ser Val Ala Leu
2245 2250 2255
Leu Tyr Ser Ser Glu Arg Ala Ser Pro Leu Glu Leu Glu Ala Ser Pro
2260 2265 2270
Thr Tyr Arg Ile Leu Glu Leu Glu Thr Tyr Arg His Ile Ser Leu Tyr
2275 2280 2285
Ser Leu Glu Ile Leu Glu Leu Glu Gly Leu Tyr Gly Leu Gly Leu Asn
2290 2295 2300
Thr His Arg Leu Tyr Ser Gly Leu Leu Glu Ile Leu Glu Ala Ser Pro
2305 2310 2315 2320
Leu Glu Val Ala Leu Thr His Arg Ser Glu Arg Thr His Arg Leu Glu
2325 2330 2335
Ala Ser Asn Ser Glu Arg Ser Glu Arg Ile Leu Glu Pro Arg Pro His
2340 2345 2350
Glu Gly Leu Leu Glu Ser Glu Arg Ser Glu Arg Thr Tyr Arg Thr His
2355 2360 2365
Arg Ala Ser Asn Ala Ser Pro Leu Tyr Ser Ile Leu Glu Leu Glu Ile
2370 2375 2380
Leu Glu Ile Leu Glu Thr Tyr Arg Pro His Glu Ala Ser Asn Ala Arg
2385 2390 2395 2400
Gly Leu Glu Thr Tyr Arg Leu Tyr Ser Leu Tyr Ser Ile Leu Glu Leu
2405 2410 2415
Tyr Ser Ala Ser Pro Ser Glu Arg Ser Glu Arg Ile Leu Glu Leu Glu
2420 2425 2430
Ala Ser Pro Met Glu Thr Ala Arg Gly Thr Tyr Arg Gly Leu Ala Ser
2435 2440 2445
Asn Ala Ser Asn Leu Tyr Ser Pro His Glu Ile Leu Glu Ala Ser Pro
2450 2455 2460
Ile Leu Glu Ser Glu Arg Gly Leu Tyr Thr Tyr Arg Gly Leu Tyr Ser
2465 2470 2475 2480
Glu Arg Ala Ser Asn Ile Leu Glu Ser Glu Arg Ile Leu Glu Ala Ser
2485 2490 2495
Asn Gly Leu Tyr Ala Ser Asn Val Ala Leu Thr Tyr Arg Ile Leu Glu
2500 2505 2510
Thr Tyr Arg Ser Glu Arg Thr His Arg Ala Ser Asn Ala Arg Gly Ala
2515 2520 2525
Ser Asn Gly Leu Asn Pro His Glu Gly Leu Tyr Ile Leu Glu Thr Tyr
2530 2535 2540
Arg Ser Glu Arg Gly Leu Tyr Ala Arg Gly Leu Glu Ser Glu Arg Gly
2545 2550 2555 2560
Leu Val Ala Leu Ala Ser Asn Ile Leu Glu Ala Leu Ala Gly Leu Asn
2565 2570 2575
Ala Ser Asn Ala Ser Asn Ala Ser Pro Ile Leu Glu Ile Leu Glu Thr
2580 2585 2590
Tyr Arg Ala Ser Asn Ser Glu Arg Ala Arg Gly Thr Tyr Arg Gly Leu
2595 2600 2605
Asn Ala Ser Asn Pro His Glu Ser Glu Arg Ile Leu Glu Ser Glu Arg
2610 2615 2620
Pro His Glu Thr Arg Pro Val Ala Leu Thr His Arg Ile Leu Glu Pro
2625 2630 2635 2640
Arg Leu Tyr Ser His Ile Ser Thr Tyr Arg Ala Arg Gly Pro Arg Met
2645 2650 2655
Glu Thr Ala Ser Asn Ala Arg Gly Ala Ser Asn Ala Arg Gly Gly Leu
2660 2665 2670
Thr Tyr Arg Thr His Arg Ile Leu Glu Ile Leu Glu Ala Ser Asn Cys
2675 2680 2685
Tyr Ser Met Glu Thr Gly Leu Tyr Ala Ser Asn Ala Ser Asn Ala Ser
2690 2695 2700
Asn Ser Glu Arg Gly Leu Tyr Thr Arg Pro Leu Tyr Ser Ile Leu Glu
2705 2710 2715 2720
Ser Glu Arg Leu Glu Ala Arg Gly Thr His Arg Ile Leu Glu Ala Arg
2725 2730 2735
Gly Ala Ser Pro Cys Tyr Ser Gly Leu Ile Leu Glu Ile Leu Glu Thr
2740 2745 2750
Arg Pro Thr His Arg Leu Glu Gly Leu Asn Ala Ser Pro Thr His Arg
2755 2760 2765
Ser Glu Arg Gly Leu Tyr Ala Ser Asn Leu Tyr Ser Gly Leu Leu Tyr
2770 2775 2780
Ser Leu Glu Ile Leu Glu Pro His Glu Ala Arg Gly Thr Tyr Arg Gly
2785 2790 2795 2800
Leu Gly Leu Leu Glu Ala Leu Ala Ser Glu Arg Ile Leu Glu Ser Glu
2805 2810 2815
Arg Ala Ser Pro Thr Tyr Arg Ile Leu Glu Ala Ser Asn Leu Tyr Ser
2820 2825 2830
Thr Arg Pro Ile Leu Glu Pro His Glu Val Ala Leu Thr His Arg Ile
2835 2840 2845
Leu Glu Thr His Arg Ala Ser Asn Ala Ser Asn Ala Arg Gly Leu Glu
2850 2855 2860
Gly Leu Tyr Ala Ser Asn Ser Glu Arg Ala Arg Gly Ile Leu Glu Thr
2865 2870 2875 2880
Tyr Arg Ile Leu Glu Ala Ser Asn Gly Leu Tyr Ala Ser Asn Leu Glu
2885 2890 2895
Ile Leu Glu Val Ala Leu Gly Leu Leu Tyr Ser Ser Glu Arg Ile Leu
2900 2905 2910
Glu Ser Glu Arg Ala Ser Asn Leu Glu Gly Leu Tyr Ala Ser Pro Ile
2915 2920 2925
Leu Glu His Ile Ser Val Ala Leu Ser Glu Arg Ala Ser Pro Ala Ser
2930 2935 2940
Asn Ile Leu Glu Leu Glu Pro His Glu Leu Tyr Ser Ile Leu Glu Val
2945 2950 2955 2960
Ala Leu Gly Leu Tyr Cys Tyr Ser Ala Ser Pro Ala Ser Pro Gly Leu
2965 2970 2975
Thr His Arg Thr Tyr Arg Val Ala Leu Gly Leu Tyr Ile Leu Glu Ala
2980 2985 2990
Arg Gly Thr Tyr Arg Pro His Glu Leu Tyr Ser Val Ala Leu Pro His
2995 3000 3005
Glu Ala Ser Asn Thr His Arg Gly Leu Leu Glu Ala Ser Pro Leu Tyr
3010 3015 3020
Ser Thr His Arg Gly Leu Ile Leu Glu Gly Leu Thr His Arg Leu Glu
3025 3030 3035 3040
Thr Tyr Arg Ser Glu Arg Ala Ser Asn Gly Leu Pro Arg Ala Ser Pro
3045 3050 3055
Pro Arg Ser Glu Arg Ile Leu Glu Leu Glu Leu Tyr Ser Ala Ser Pro
3060 3065 3070
Thr Tyr Arg Thr Arg Pro Gly Leu Tyr Ala Ser Asn Thr Tyr Arg Leu
3075 3080 3085
Glu Leu Glu Thr Tyr Arg Ala Ser Asn Leu Tyr Ser Leu Tyr Ser Thr
3090 3095 3100
Tyr Arg Thr Tyr Arg Leu Glu Pro His Glu Ala Ser Asn Leu Glu Leu
3105 3110 3115 3120
Glu Ala Arg Gly Leu Tyr Ser Ala Ser Pro Leu Tyr Ser Thr Tyr Arg
3125 3130 3135
Ile Leu Glu Thr His Arg Ala Arg Gly Ala Ser Asn Ser Glu Arg Gly
3140 3145 3150
Leu Tyr Ile Leu Glu Leu Glu Ala Ser Asn Ile Leu Glu Ala Ser Asn
3155 3160 3165
Gly Leu Asn Gly Leu Asn Ala Arg Gly Gly Leu Tyr Val Ala Leu Thr
3170 3175 3180
His Arg Gly Leu Tyr Gly Leu Tyr Ile Leu Glu Ser Glu Arg Val Ala
3185 3190 3195 3200
Leu Pro His Glu Leu Glu Ala Ser Asn Thr Tyr Arg Leu Tyr Ser Leu
3205 3210 3215
Glu Thr Tyr Arg Gly Leu Gly Leu Tyr Val Ala Leu Gly Leu Val Ala
3220 3225 3230
Leu Ile Leu Glu Ile Leu Glu Ala Arg Gly Leu Tyr Ser Ala Ser Asn
3235 3240 3245
Ala Leu Ala Pro Arg Ile Leu Glu Ala Ser Pro Ile Leu Glu Ser Glu
3250 3255 3260
Arg Ala Ser Asn Thr His Arg Ala Ser Pro Ala Ser Asn Pro His Glu
3265 3270 3275 3280
Val Ala Leu Ala Arg Gly Leu Tyr Ser Ala Ser Asn Ala Ser Pro Leu
3285 3290 3295
Glu Ala Leu Ala Thr Tyr Arg Ile Leu Glu Ala Ser Asn Val Ala Leu
3300 3305 3310
Val Ala Leu Ala Ser Pro His Ile Ser Gly Leu Tyr Val Ala Leu Gly
3315 3320 3325
Leu Thr Tyr Arg Ala Arg Gly Leu Glu Thr Tyr Arg Ala Leu Ala Ala
3330 3335 3340
Ser Pro Ile Leu Glu Ser Glu Arg Ile Leu Glu Thr His Arg Leu Tyr
3345 3350 3355 3360
Ser Ser Glu Arg Gly Leu Leu Tyr Ser Ile Leu Glu Ile Leu Glu Leu
3365 3370 3375
Tyr Ser Leu Glu Ile Leu Glu Ala Arg Gly Thr His Arg Ser Glu Arg
3380 3385 3390
Ala Ser Asn Pro Arg Ala Ser Asn Ala Ser Pro Ser Glu Arg Leu Glu
3395 3400 3405
Gly Leu Tyr Gly Leu Asn Ile Leu Glu Ile Leu Glu Val Ala Leu Met
3410 3415 3420
Glu Thr Ala Ser Pro Ser Glu Arg Ile Leu Glu Gly Leu Tyr Ala Ser
3425 3430 3435 3440
Asn Ala Ser Asn Cys Tyr Ser Thr His Arg Met Glu Thr Ala Ser Asn
3445 3450 3455
Pro His Glu Gly Leu Asn Ala Ser Asn Ala Ser Asn Ala Ser Pro Gly
3460 3465 3470
Leu Tyr Ser Glu Arg Ala Ser Asn Ile Leu Glu Gly Leu Tyr Leu Glu
3475 3480 3485
Leu Glu Gly Leu Tyr Pro His Glu His Ile Ser Ser Glu Arg Ala Ser
3490 3495 3500
Pro Ala Ser Pro Leu Glu Val Ala Leu Ala Leu Ala Ser Glu Arg Ser
3505 3510 3515 3520
Glu Arg Thr Arg Pro Thr Tyr Arg Thr Tyr Arg Ala Ser Asn His Ile
3525 3530 3535
Ser Ile Leu Glu Ala Arg Gly Ala Arg Gly Ala Ser Asn Thr His Arg
3540 3545 3550
Ser Glu Arg Ser Glu Arg Ala Ser Asn Gly Leu Tyr Cys Tyr Ser Pro
3555 3560 3565
His Glu Thr Arg Pro Ser Glu Arg Pro His Glu Ile Leu Glu Ser Glu
3570 3575 3580
Arg Leu Tyr Ser Gly Leu His Ile Ser Gly Leu Tyr Thr Arg Pro Leu
3585 3590 3595 3600
Tyr Ser Gly Leu
<210> 13
<211> 3894
<212> DNA
<213> Clostridium botulinum
<220>
<221> misc_feature
<222> (20)
<223> n is a, c, g, or t
<400> 13
atgccagtta atataaaaan ctttaattat aatgacccta ttaataatga tgacattatt 60
atgatggaac cattcaatga cccagggcca ggaacatatt ataaagcttt taggattata 120
gatcgtattt ggatagtacc agaaaggttt acttatggat ttcaacctga ccaatttaat 180
gccagtacag gagtttttag taaagatgtc tacgaatatt acgatccaac ttatttaaaa 240
accgatgctg aaaaagataa atttttaaaa acaatgatta aattatttaa tagaattaat 300
tcaaaaccat caggacagag attactggat atgatagtag atgctatacc ttatcttgga 360
aatgcatcta caccgcccga caaatttgca gcaaatgttg caaatgtatc tattaataaa 420
aaaattatcc aacctggagc tgaagatcaa ataaaaggtt taatgacaaa tttaataata 480
tttggaccag gaccagttct aagtgataat tttactgata gtatgattat gaatggccat 540
tccccaatat cagaaggatt tggtgcaaga atgatgataa gattttgtcc tagttgttta 600
aatgtattta ataatgttca ggaaaataaa gatacatcta tatttagtag acgcgcgtat 660
tttgcagatc cagctctaac gttaatgcat gaacttatac atgtgttaca tggattatat 720
ggaattaaga taagtaattt accaattact ccaaatacaa aagaattttt catgcaacat 780
agcgatcctg tacaagcaga agaactatat acattcggag gacatgatcc tagtgttata 840
agtccttcta cggatatgaa tatttataat aaagcgttac aaaattttca agatatagct 900
aataggctta atattgtttc aagtgcccaa gggagtggaa ttgatatttc cttatataaa 960
caaatatata aaaataaata tgattttgtt gaagatccta atggaaaata tagtgtagat 1020
aaggataagt ttgataaatt atataaggcc ttaatgtttg gctttactga aactaatcta 1080
gctggtgaat atggaataaa aactaggtat tcttatttta gtgaatattt gccaccgata 1140
aaaactgaaa aattgttaga caatacaatt tatactcaaa atgaaggctt taacatagct 1200
agtaaaaatc tcaaaacgga atttaatggt cagaataagg cggtaaataa agaggcttat 1260
gaagaaatca gcctagaaca tctcgttata tatagaatag caatgtgcaa gcctgtaatg 1320
tacaaaaata ccggtaaatc tgaacagtgt attattgtta ataatgagga tttatttttc 1380
atagctaata aagatagttt ttcaaaagat ttagctaaag cagaaactat agcatataat 1440
acacaaaata atactataga aaataatttt tctatagatc agttgatttt agataatgat 1500
ttaagcagtg gcatagactt accaaatgaa aacacagaac catttacaaa ttttgacgac 1560
atagatatcc ctgtgtatat taaacaatct gctttaaaaa aaatttttgt ggatggagat 1620
agcctttttg aatatttaca tgctcaaaca tttccttcta atatagaaaa tctacaacta 1680
acgaattcat taaatgatgc tttaagaaat aataataaag tctatacttt tttttctaca 1740
aaccttgttg aaaaagctaa tacagttgta ggtgcttcac tttttgtaaa ctgggtaaaa 1800
ggagtaatag atgattttac atctgaatcc acacaaaaaa gtactataga taaagtttca 1860
gatgtatcca taattattcc ctatatagga cctgctttga atgtaggaaa tgaaacagct 1920
aaagaaaatt ttaaaaatgc ttttgaaata ggtggagccg ctatcttaat ggagtttatt 1980
ccagaactta ttgtacctat agttggattt tttacattag aatcatatgt aggaaataaa 2040
gggcatatta ttatgacgat atccaatgct ttaaagaaaa gggatcaaaa atggacagat 2100
atgtatggtt tgatagtatc gcagtggctc tcaacggtta atactcaatt ttatacaata 2160
aaagaaagaa tgtacaatgc tttaaataat caatcacaag caatagaaaa aataatagaa 2220
gatcaatata atagatatag tgaagaagat aaaatgaata ttaacattga ttttaatgat 2280
atagatttta aacttaatca aagtataaat ttagcaataa acaatataga tgattttata 2340
aaccaatgtt ctatatcata tctaatgaat agaatgattc cattagctgt aaaaaagtta 2400
aaagactttg atgataatct taagagagat ttattggagt atatagatac aaatgaacta 2460
tatttacttg atgaagtaaa tattctaaaa tcaaaagtaa atagacacct aaaagacagt 2520
ataccatttg atctttcact atataccaag gacacaattt taatacaagt ttttaataat 2580
tatattagta atattagtag taatgctatt ttaagtttaa gttatagagg tgggcgttta 2640
atagattcat ctggatatgg tgcaactatg aatgtaggtt cagatgttat ctttaatgat 2700
ataggaaatg gtcaatttaa attaaataat tctgaaaata gtaatattac ggcacatcaa 2760
agtaaattcg ttgtatatga tagtatgttt gataatttta gcattaactt ttgggtaagg 2820
actcctaaat ataataataa tgatatacaa acttatcttc aaaatgagta tacaataatt 2880
agttgtataa aaaatgactc aggatggaaa gtatctatta agggaaatag aataatatgg 2940
acattaatag atgttaatgc aaaatctaaa tcaatatttt tcgaatatag tataaaagat 3000
aatatatcag attatataaa taaatggttt tccataacta ttactaatga tagattaggt 3060
aacgcaaata tttatataaa tggaagtttg aaaaaaagtg aaaaaatttt aaacttagat 3120
agaattaatt ctagtaatga tatagacttc aaattaatta attgtacaga tactactaaa 3180
tttgtttgga ttaaggattt taatattttt ggtagagaat taaatgctac agaagtatct 3240
tcactatatt ggattcaatc atctacaaat actttaaaag atttttgggg gaatccttta 3300
agatacgata cacaatacta tctgtttaat caaggtatgc aaaatatcta tataaagtat 3360
tttagtaaag cttctatggg ggaaactgca ccacgtacaa actttaataa tgcagcaata 3420
aattatcaaa atttatatct tggtttacga tttattataa aaaaagcatc aaattctcgg 3480
aatataaata atgataatat agtcagagaa ggagattata tatatcttaa tattgataat 3540
atttctgatg aatcttacag agtatatgtt ttggtgaatt ctaaagaaat tcaaactcaa 3600
ttatttttag cacccataaa tgatgatcct acgttctatg atgtactaca aataaaaaaa 3660
tattatgaaa aaacaacata taattgtcag atactttgcg aaaaagatac taaaacattt 3720
gggctgtttg gaattggtaa atttgttaaa gattatggat atgtttggga tacctatgat 3780
aattattttt gcataagtca gtggtatctc agaagaatat ctgaaaatat aaataaatta 3840
aggttgggat gtaattggca attcattccc gtggatgaag gatggacaga ataa 3894
<210> 14
<211> 3690
<212> PRT
<213> Clostridium botulinum
<220>
<221> MISC_FEATURE
<222> (18)
<223> Xaa can be any naturally occurring amino acid
<400> 14
Met Glu Thr Pro Arg Val Ala Leu Ala Ser Asn Ile Leu Glu Leu Tyr
1 5 10 15
Ser Xaa Ala Ala Pro His Glu Ala Ser Asn Thr Tyr Arg Ala Ser Asn
20 25 30
Ala Ser Pro Pro Arg Ile Leu Glu Ala Ser Asn Ala Ser Asn Ala Ser
35 40 45
Pro Ala Ser Pro Ile Leu Glu Ile Leu Glu Met Glu Thr Met Glu Thr
50 55 60
Gly Leu Pro Arg Pro His Glu Ala Ser Asn Ala Ser Pro Pro Arg Gly
65 70 75 80
Leu Tyr Pro Arg Gly Leu Tyr Thr His Arg Thr Tyr Arg Thr Tyr Arg
85 90 95
Leu Tyr Ser Ala Leu Ala Pro His Glu Ala Arg Gly Ile Leu Glu Ile
100 105 110
Leu Glu Ala Ser Pro Ala Arg Gly Ile Leu Glu Thr Arg Pro Ile Leu
115 120 125
Glu Val Ala Leu Pro Arg Gly Leu Ala Arg Gly Pro His Glu Thr His
130 135 140
Arg Thr Tyr Arg Gly Leu Tyr Pro His Glu Gly Leu Asn Pro Arg Ala
145 150 155 160
Ser Pro Gly Leu Asn Pro His Glu Ala Ser Asn Ala Leu Ala Ser Glu
165 170 175
Arg Thr His Arg Gly Leu Tyr Val Ala Leu Pro His Glu Ser Glu Arg
180 185 190
Leu Tyr Ser Ala Ser Pro Val Ala Leu Thr Tyr Arg Gly Leu Thr Tyr
195 200 205
Arg Thr Tyr Arg Ala Ser Pro Pro Arg Thr His Arg Thr Tyr Arg Leu
210 215 220
Glu Leu Tyr Ser Thr His Arg Ala Ser Pro Ala Leu Ala Gly Leu Leu
225 230 235 240
Tyr Ser Ala Ser Pro Leu Tyr Ser Pro His Glu Leu Glu Leu Tyr Ser
245 250 255
Thr His Arg Met Glu Thr Ile Leu Glu Leu Tyr Ser Leu Glu Pro His
260 265 270
Glu Ala Ser Asn Ala Arg Gly Ile Leu Glu Ala Ser Asn Ser Glu Arg
275 280 285
Leu Tyr Ser Pro Arg Ser Glu Arg Gly Leu Tyr Gly Leu Asn Ala Arg
290 295 300
Gly Leu Glu Leu Glu Ala Ser Pro Met Glu Thr Ile Leu Glu Val Ala
305 310 315 320
Leu Ala Ser Pro Ala Leu Ala Ile Leu Glu Pro Arg Thr Tyr Arg Leu
325 330 335
Glu Gly Leu Tyr Ala Ser Asn Ala Leu Ala Ser Glu Arg Thr His Arg
340 345 350
Pro Arg Pro Arg Ala Ser Pro Leu Tyr Ser Pro His Glu Ala Leu Ala
355 360 365
Ala Leu Ala Ala Ser Asn Val Ala Leu Ala Leu Ala Ala Ser Asn Val
370 375 380
Ala Leu Ser Glu Arg Ile Leu Glu Ala Ser Asn Leu Tyr Ser Leu Tyr
385 390 395 400
Ser Ile Leu Glu Ile Leu Glu Gly Leu Asn Pro Arg Gly Leu Tyr Ala
405 410 415
Leu Ala Gly Leu Ala Ser Pro Gly Leu Asn Ile Leu Glu Leu Tyr Ser
420 425 430
Gly Leu Tyr Leu Glu Met Glu Thr Thr His Arg Ala Ser Asn Leu Glu
435 440 445
Ile Leu Glu Ile Leu Glu Pro His Glu Gly Leu Tyr Pro Arg Gly Leu
450 455 460
Tyr Pro Arg Val Ala Leu Leu Glu Ser Glu Arg Ala Ser Pro Ala Ser
465 470 475 480
Asn Pro His Glu Thr His Arg Ala Ser Pro Ser Glu Arg Met Glu Thr
485 490 495
Ile Leu Glu Met Glu Thr Ala Ser Asn Gly Leu Tyr His Ile Ser Ser
500 505 510
Glu Arg Pro Arg Ile Leu Glu Ser Glu Arg Gly Leu Gly Leu Tyr Pro
515 520 525
His Glu Gly Leu Tyr Ala Leu Ala Ala Arg Gly Met Glu Thr Met Glu
530 535 540
Thr Ile Leu Glu Ala Arg Gly Pro His Glu Cys Tyr Ser Pro Arg Ser
545 550 555 560
Glu Arg Cys Tyr Ser Leu Glu Ala Ser Asn Val Ala Leu Pro His Glu
565 570 575
Ala Ser Asn Ala Ser Asn Val Ala Leu Gly Leu Asn Gly Leu Ala Ser
580 585 590
Asn Leu Tyr Ser Ala Ser Pro Thr His Arg Ser Glu Arg Ile Leu Glu
595 600 605
Pro His Glu Ser Glu Arg Ala Arg Gly Ala Arg Gly Ala Leu Ala Thr
610 615 620
Tyr Arg Pro His Glu Ala Leu Ala Ala Ser Pro Pro Arg Ala Leu Ala
625 630 635 640
Leu Glu Thr His Arg Leu Glu Met Glu Thr His Ile Ser Gly Leu Leu
645 650 655
Glu Ile Leu Glu His Ile Ser Val Ala Leu Leu Glu His Ile Ser Gly
660 665 670
Leu Tyr Leu Glu Thr Tyr Arg Gly Leu Tyr Ile Leu Glu Leu Tyr Ser
675 680 685
Ile Leu Glu Ser Glu Arg Ala Ser Asn Leu Glu Pro Arg Ile Leu Glu
690 695 700
Thr His Arg Pro Arg Ala Ser Asn Thr His Arg Leu Tyr Ser Gly Leu
705 710 715 720
Pro His Glu Pro His Glu Met Glu Thr Gly Leu Asn His Ile Ser Ser
725 730 735
Glu Arg Ala Ser Pro Pro Arg Val Ala Leu Gly Leu Asn Ala Leu Ala
740 745 750
Gly Leu Gly Leu Leu Glu Thr Tyr Arg Thr His Arg Pro His Glu Gly
755 760 765
Leu Tyr Gly Leu Tyr His Ile Ser Ala Ser Pro Pro Arg Ser Glu Arg
770 775 780
Val Ala Leu Ile Leu Glu Ser Glu Arg Pro Arg Ser Glu Arg Thr His
785 790 795 800
Arg Ala Ser Pro Met Glu Thr Ala Ser Asn Ile Leu Glu Thr Tyr Arg
805 810 815
Ala Ser Asn Leu Tyr Ser Ala Leu Ala Leu Glu Gly Leu Asn Ala Ser
820 825 830
Asn Pro His Glu Gly Leu Asn Ala Ser Pro Ile Leu Glu Ala Leu Ala
835 840 845
Ala Ser Asn Ala Arg Gly Leu Glu Ala Ser Asn Ile Leu Glu Val Ala
850 855 860
Leu Ser Glu Arg Ser Glu Arg Ala Leu Ala Gly Leu Asn Gly Leu Tyr
865 870 875 880
Ser Glu Arg Gly Leu Tyr Ile Leu Glu Ala Ser Pro Ile Leu Glu Ser
885 890 895
Glu Arg Leu Glu Thr Tyr Arg Leu Tyr Ser Gly Leu Asn Ile Leu Glu
900 905 910
Thr Tyr Arg Leu Tyr Ser Ala Ser Asn Leu Tyr Ser Thr Tyr Arg Ala
915 920 925
Ser Pro Pro His Glu Val Ala Leu Gly Leu Ala Ser Pro Pro Arg Ala
930 935 940
Ser Asn Gly Leu Tyr Leu Tyr Ser Thr Tyr Arg Ser Glu Arg Val Ala
945 950 955 960
Leu Ala Ser Pro Leu Tyr Ser Ala Ser Pro Leu Tyr Ser Pro His Glu
965 970 975
Ala Ser Pro Leu Tyr Ser Leu Glu Thr Tyr Arg Leu Tyr Ser Ala Leu
980 985 990
Ala Leu Glu Met Glu Thr Pro His Glu Gly Leu Tyr Pro His Glu Thr
995 1000 1005
His Arg Gly Leu Thr His Arg Ala Ser Asn Leu Glu Ala Leu Ala Gly
1010 1015 1020
Leu Tyr Gly Leu Thr Tyr Arg Gly Leu Tyr Ile Leu Glu Leu Tyr Ser
1025 1030 1035 1040
Thr His Arg Ala Arg Gly Thr Tyr Arg Ser Glu Arg Thr Tyr Arg Pro
1045 1050 1055
His Glu Ser Glu Arg Gly Leu Thr Tyr Arg Leu Glu Pro Arg Pro Arg
1060 1065 1070
Ile Leu Glu Leu Tyr Ser Thr His Arg Gly Leu Leu Tyr Ser Leu Glu
1075 1080 1085
Leu Glu Ala Ser Pro Ala Ser Asn Thr His Arg Ile Leu Glu Thr Tyr
1090 1095 1100
Arg Thr His Arg Gly Leu Asn Ala Ser Asn Gly Leu Gly Leu Tyr Pro
1105 1110 1115 1120
His Glu Ala Ser Asn Ile Leu Glu Ala Leu Ala Ser Glu Arg Leu Tyr
1125 1130 1135
Ser Ala Ser Asn Leu Glu Leu Tyr Ser Thr His Arg Gly Leu Pro His
1140 1145 1150
Glu Ala Ser Asn Gly Leu Tyr Gly Leu Asn Ala Ser Asn Leu Tyr Ser
1155 1160 1165
Ala Leu Ala Val Ala Leu Ala Ser Asn Leu Tyr Ser Gly Leu Ala Leu
1170 1175 1180
Ala Thr Tyr Arg Gly Leu Gly Leu Ile Leu Glu Ser Glu Arg Leu Glu
1185 1190 1195 1200
Gly Leu His Ile Ser Leu Glu Val Ala Leu Ile Leu Glu Thr Tyr Arg
1205 1210 1215
Ala Arg Gly Ile Leu Glu Ala Leu Ala Met Glu Thr Cys Tyr Ser Leu
1220 1225 1230
Tyr Ser Pro Arg Val Ala Leu Met Glu Thr Thr Tyr Arg Leu Tyr Ser
1235 1240 1245
Ala Ser Asn Thr His Arg Gly Leu Tyr Leu Tyr Ser Ser Glu Arg Gly
1250 1255 1260
Leu Gly Leu Asn Cys Tyr Ser Ile Leu Glu Ile Leu Glu Val Ala Leu
1265 1270 1275 1280
Ala Ser Asn Ala Ser Asn Gly Leu Ala Ser Pro Leu Glu Pro His Glu
1285 1290 1295
Pro His Glu Ile Leu Glu Ala Leu Ala Ala Ser Asn Leu Tyr Ser Ala
1300 1305 1310
Ser Pro Ser Glu Arg Pro His Glu Ser Glu Arg Leu Tyr Ser Ala Ser
1315 1320 1325
Pro Leu Glu Ala Leu Ala Leu Tyr Ser Ala Leu Ala Gly Leu Thr His
1330 1335 1340
Arg Ile Leu Glu Ala Leu Ala Thr Tyr Arg Ala Ser Asn Thr His Arg
1345 1350 1355 1360
Gly Leu Asn Ala Ser Asn Ala Ser Asn Thr His Arg Ile Leu Glu Gly
1365 1370 1375
Leu Ala Ser Asn Ala Ser Asn Pro His Glu Ser Glu Arg Ile Leu Glu
1380 1385 1390
Ala Ser Pro Gly Leu Asn Leu Glu Ile Leu Glu Leu Glu Ala Ser Pro
1395 1400 1405
Ala Ser Asn Ala Ser Pro Leu Glu Ser Glu Arg Ser Glu Arg Gly Leu
1410 1415 1420
Tyr Ile Leu Glu Ala Ser Pro Leu Glu Pro Arg Ala Ser Asn Gly Leu
1425 1430 1435 1440
Ala Ser Asn Thr His Arg Gly Leu Pro Arg Pro His Glu Thr His Arg
1445 1450 1455
Ala Ser Asn Pro His Glu Ala Ser Pro Ala Ser Pro Ile Leu Glu Ala
1460 1465 1470
Ser Pro Ile Leu Glu Pro Arg Val Ala Leu Thr Tyr Arg Ile Leu Glu
1475 1480 1485
Leu Tyr Ser Gly Leu Asn Ser Glu Arg Ala Leu Ala Leu Glu Leu Tyr
1490 1495 1500
Ser Leu Tyr Ser Ile Leu Glu Pro His Glu Val Ala Leu Ala Ser Pro
1505 1510 1515 1520
Gly Leu Tyr Ala Ser Pro Ser Glu Arg Leu Glu Pro His Glu Gly Leu
1525 1530 1535
Thr Tyr Arg Leu Glu His Ile Ser Ala Leu Ala Gly Leu Asn Thr His
1540 1545 1550
Arg Pro His Glu Pro Arg Ser Glu Arg Ala Ser Asn Ile Leu Glu Gly
1555 1560 1565
Leu Ala Ser Asn Leu Glu Gly Leu Asn Leu Glu Thr His Arg Ala Ser
1570 1575 1580
Asn Ser Glu Arg Leu Glu Ala Ser Asn Ala Ser Pro Ala Leu Ala Leu
1585 1590 1595 1600
Glu Ala Arg Gly Ala Ser Asn Ala Ser Asn Ala Ser Asn Leu Tyr Ser
1605 1610 1615
Val Ala Leu Thr Tyr Arg Thr His Arg Pro His Glu Pro His Glu Ser
1620 1625 1630
Glu Arg Thr His Arg Ala Ser Asn Leu Glu Val Ala Leu Gly Leu Leu
1635 1640 1645
Tyr Ser Ala Leu Ala Ala Ser Asn Thr His Arg Val Ala Leu Val Ala
1650 1655 1660
Leu Gly Leu Tyr Ala Leu Ala Ser Glu Arg Leu Glu Pro His Glu Val
1665 1670 1675 1680
Ala Leu Ala Ser Asn Thr Arg Pro Val Ala Leu Leu Tyr Ser Gly Leu
1685 1690 1695
Tyr Val Ala Leu Ile Leu Glu Ala Ser Pro Ala Ser Pro Pro His Glu
1700 1705 1710
Thr His Arg Ser Glu Arg Gly Leu Ser Glu Arg Thr His Arg Gly Leu
1715 1720 1725
Asn Leu Tyr Ser Ser Glu Arg Thr His Arg Ile Leu Glu Ala Ser Pro
1730 1735 1740
Leu Tyr Ser Val Ala Leu Ser Glu Arg Ala Ser Pro Val Ala Leu Ser
1745 1750 1755 1760
Glu Arg Ile Leu Glu Ile Leu Glu Ile Leu Glu Pro Arg Thr Tyr Arg
1765 1770 1775
Ile Leu Glu Gly Leu Tyr Pro Arg Ala Leu Ala Leu Glu Ala Ser Asn
1780 1785 1790
Val Ala Leu Gly Leu Tyr Ala Ser Asn Gly Leu Thr His Arg Ala Leu
1795 1800 1805
Ala Leu Tyr Ser Gly Leu Ala Ser Asn Pro His Glu Leu Tyr Ser Ala
1810 1815 1820
Ser Asn Ala Leu Ala Pro His Glu Gly Leu Ile Leu Glu Gly Leu Tyr
1825 1830 1835 1840
Gly Leu Tyr Ala Leu Ala Ala Leu Ala Ile Leu Glu Leu Glu Met Glu
1845 1850 1855
Thr Gly Leu Pro His Glu Ile Leu Glu Pro Arg Gly Leu Leu Glu Ile
1860 1865 1870
Leu Glu Val Ala Leu Pro Arg Ile Leu Glu Val Ala Leu Gly Leu Tyr
1875 1880 1885
Pro His Glu Pro His Glu Thr His Arg Leu Glu Gly Leu Ser Glu Arg
1890 1895 1900
Thr Tyr Arg Val Ala Leu Gly Leu Tyr Ala Ser Asn Leu Tyr Ser Gly
1905 1910 1915 1920
Leu Tyr His Ile Ser Ile Leu Glu Ile Leu Glu Met Glu Thr Thr His
1925 1930 1935
Arg Ile Leu Glu Ser Glu Arg Ala Ser Asn Ala Leu Ala Leu Glu Leu
1940 1945 1950
Tyr Ser Leu Tyr Ser Ala Arg Gly Ala Ser Pro Gly Leu Asn Leu Tyr
1955 1960 1965
Ser Thr Arg Pro Thr His Arg Ala Ser Pro Met Glu Thr Thr Tyr Arg
1970 1975 1980
Gly Leu Tyr Leu Glu Ile Leu Glu Val Ala Leu Ser Glu Arg Gly Leu
1985 1990 1995 2000
Asn Thr Arg Pro Leu Glu Ser Glu Arg Thr His Arg Val Ala Leu Ala
2005 2010 2015
Ser Asn Thr His Arg Gly Leu Asn Pro His Glu Thr Tyr Arg Thr His
2020 2025 2030
Arg Ile Leu Glu Leu Tyr Ser Gly Leu Ala Arg Gly Met Glu Thr Thr
2035 2040 2045
Tyr Arg Ala Ser Asn Ala Leu Ala Leu Glu Ala Ser Asn Ala Ser Asn
2050 2055 2060
Gly Leu Asn Ser Glu Arg Gly Leu Asn Ala Leu Ala Ile Leu Glu Gly
2065 2070 2075 2080
Leu Leu Tyr Ser Ile Leu Glu Ile Leu Glu Gly Leu Ala Ser Pro Gly
2085 2090 2095
Leu Asn Thr Tyr Arg Ala Ser Asn Ala Arg Gly Thr Tyr Arg Ser Glu
2100 2105 2110
Arg Gly Leu Gly Leu Ala Ser Pro Leu Tyr Ser Met Glu Thr Ala Ser
2115 2120 2125
Asn Ile Leu Glu Ala Ser Asn Ile Leu Glu Ala Ser Pro Pro His Glu
2130 2135 2140
Ala Ser Asn Ala Ser Pro Ile Leu Glu Ala Ser Pro Pro His Glu Leu
2145 2150 2155 2160
Tyr Ser Leu Glu Ala Ser Asn Gly Leu Asn Ser Glu Arg Ile Leu Glu
2165 2170 2175
Ala Ser Asn Leu Glu Ala Leu Ala Ile Leu Glu Ala Ser Asn Ala Ser
2180 2185 2190
Asn Ile Leu Glu Ala Ser Pro Ala Ser Pro Pro His Glu Ile Leu Glu
2195 2200 2205
Ala Ser Asn Gly Leu Asn Cys Tyr Ser Ser Glu Arg Ile Leu Glu Ser
2210 2215 2220
Glu Arg Thr Tyr Arg Leu Glu Met Glu Thr Ala Ser Asn Ala Arg Gly
2225 2230 2235 2240
Met Glu Thr Ile Leu Glu Pro Arg Leu Glu Ala Leu Ala Val Ala Leu
2245 2250 2255
Leu Tyr Ser Leu Tyr Ser Leu Glu Leu Tyr Ser Ala Ser Pro Pro His
2260 2265 2270
Glu Ala Ser Pro Ala Ser Pro Ala Ser Asn Leu Glu Leu Tyr Ser Ala
2275 2280 2285
Arg Gly Ala Ser Pro Leu Glu Leu Glu Gly Leu Thr Tyr Arg Ile Leu
2290 2295 2300
Glu Ala Ser Pro Thr His Arg Ala Ser Asn Gly Leu Leu Glu Thr Tyr
2305 2310 2315 2320
Arg Leu Glu Leu Glu Ala Ser Pro Gly Leu Val Ala Leu Ala Ser Asn
2325 2330 2335
Ile Leu Glu Leu Glu Leu Tyr Ser Ser Glu Arg Leu Tyr Ser Val Ala
2340 2345 2350
Leu Ala Ser Asn Ala Arg Gly His Ile Ser Leu Glu Leu Tyr Ser Ala
2355 2360 2365
Ser Pro Ser Glu Arg Ile Leu Glu Pro Arg Pro His Glu Ala Ser Pro
2370 2375 2380
Leu Glu Ser Glu Arg Leu Glu Thr Tyr Arg Thr His Arg Leu Tyr Ser
2385 2390 2395 2400
Ala Ser Pro Thr His Arg Ile Leu Glu Leu Glu Ile Leu Glu Gly Leu
2405 2410 2415
Asn Val Ala Leu Pro His Glu Ala Ser Asn Ala Ser Asn Thr Tyr Arg
2420 2425 2430
Ile Leu Glu Ser Glu Arg Ala Ser Asn Ile Leu Glu Ser Glu Arg Ser
2435 2440 2445
Glu Arg Ala Ser Asn Ala Leu Ala Ile Leu Glu Leu Glu Ser Glu Arg
2450 2455 2460
Leu Glu Ser Glu Arg Thr Tyr Arg Ala Arg Gly Gly Leu Tyr Gly Leu
2465 2470 2475 2480
Tyr Ala Arg Gly Leu Glu Ile Leu Glu Ala Ser Pro Ser Glu Arg Ser
2485 2490 2495
Glu Arg Gly Leu Tyr Thr Tyr Arg Gly Leu Tyr Ala Leu Ala Thr His
2500 2505 2510
Arg Met Glu Thr Ala Ser Asn Val Ala Leu Gly Leu Tyr Ser Glu Arg
2515 2520 2525
Ala Ser Pro Val Ala Leu Ile Leu Glu Pro His Glu Ala Ser Asn Ala
2530 2535 2540
Ser Pro Ile Leu Glu Gly Leu Tyr Ala Ser Asn Gly Leu Tyr Gly Leu
2545 2550 2555 2560
Asn Pro His Glu Leu Tyr Ser Leu Glu Ala Ser Asn Ala Ser Asn Ser
2565 2570 2575
Glu Arg Gly Leu Ala Ser Asn Ser Glu Arg Ala Ser Asn Ile Leu Glu
2580 2585 2590
Thr His Arg Ala Leu Ala His Ile Ser Gly Leu Asn Ser Glu Arg Leu
2595 2600 2605
Tyr Ser Pro His Glu Val Ala Leu Val Ala Leu Thr Tyr Arg Ala Ser
2610 2615 2620
Pro Ser Glu Arg Met Glu Thr Pro His Glu Ala Ser Pro Ala Ser Asn
2625 2630 2635 2640
Pro His Glu Ser Glu Arg Ile Leu Glu Ala Ser Asn Pro His Glu Thr
2645 2650 2655
Arg Pro Val Ala Leu Ala Arg Gly Thr His Arg Pro Arg Leu Tyr Ser
2660 2665 2670
Thr Tyr Arg Ala Ser Asn Ala Ser Asn Ala Ser Asn Ala Ser Pro Ile
2675 2680 2685
Leu Glu Gly Leu Asn Thr His Arg Thr Tyr Arg Leu Glu Gly Leu Asn
2690 2695 2700
Ala Ser Asn Gly Leu Thr Tyr Arg Thr His Arg Ile Leu Glu Ile Leu
2705 2710 2715 2720
Glu Ser Glu Arg Cys Tyr Ser Ile Leu Glu Leu Tyr Ser Ala Ser Asn
2725 2730 2735
Ala Ser Pro Ser Glu Arg Gly Leu Tyr Thr Arg Pro Leu Tyr Ser Val
2740 2745 2750
Ala Leu Ser Glu Arg Ile Leu Glu Leu Tyr Ser Gly Leu Tyr Ala Ser
2755 2760 2765
Asn Ala Arg Gly Ile Leu Glu Ile Leu Glu Thr Arg Pro Thr His Arg
2770 2775 2780
Leu Glu Ile Leu Glu Ala Ser Pro Val Ala Leu Ala Ser Asn Ala Leu
2785 2790 2795 2800
Ala Leu Tyr Ser Ser Glu Arg Leu Tyr Ser Ser Glu Arg Ile Leu Glu
2805 2810 2815
Pro His Glu Pro His Glu Gly Leu Thr Tyr Arg Ser Glu Arg Ile Leu
2820 2825 2830
Glu Leu Tyr Ser Ala Ser Pro Ala Ser Asn Ile Leu Glu Ser Glu Arg
2835 2840 2845
Ala Ser Pro Thr Tyr Arg Ile Leu Glu Ala Ser Asn Leu Tyr Ser Thr
2850 2855 2860
Arg Pro Pro His Glu Ser Glu Arg Ile Leu Glu Thr His Arg Ile Leu
2865 2870 2875 2880
Glu Thr His Arg Ala Ser Asn Ala Ser Pro Ala Arg Gly Leu Glu Gly
2885 2890 2895
Leu Tyr Ala Ser Asn Ala Leu Ala Ala Ser Asn Ile Leu Glu Thr Tyr
2900 2905 2910
Arg Ile Leu Glu Ala Ser Asn Gly Leu Tyr Ser Glu Arg Leu Glu Leu
2915 2920 2925
Tyr Ser Leu Tyr Ser Ser Glu Arg Gly Leu Leu Tyr Ser Ile Leu Glu
2930 2935 2940
Leu Glu Ala Ser Asn Leu Glu Ala Ser Pro Ala Arg Gly Ile Leu Glu
2945 2950 2955 2960
Ala Ser Asn Ser Glu Arg Ser Glu Arg Ala Ser Asn Ala Ser Pro Ile
2965 2970 2975
Leu Glu Ala Ser Pro Pro His Glu Leu Tyr Ser Leu Glu Ile Leu Glu
2980 2985 2990
Ala Ser Asn Cys Tyr Ser Thr His Arg Ala Ser Pro Thr His Arg Thr
2995 3000 3005
His Arg Leu Tyr Ser Pro His Glu Val Ala Leu Thr Arg Pro Ile Leu
3010 3015 3020
Glu Leu Tyr Ser Ala Ser Pro Pro His Glu Ala Ser Asn Ile Leu Glu
3025 3030 3035 3040
Pro His Glu Gly Leu Tyr Ala Arg Gly Gly Leu Leu Glu Ala Ser Asn
3045 3050 3055
Ala Leu Ala Thr His Arg Gly Leu Val Ala Leu Ser Glu Arg Ser Glu
3060 3065 3070
Arg Leu Glu Thr Tyr Arg Thr Arg Pro Ile Leu Glu Gly Leu Asn Ser
3075 3080 3085
Glu Arg Ser Glu Arg Thr His Arg Ala Ser Asn Thr His Arg Leu Glu
3090 3095 3100
Leu Tyr Ser Ala Ser Pro Pro His Glu Thr Arg Pro Gly Leu Tyr Ala
3105 3110 3115 3120
Ser Asn Pro Arg Leu Glu Ala Arg Gly Thr Tyr Arg Ala Ser Pro Thr
3125 3130 3135
His Arg Gly Leu Asn Thr Tyr Arg Thr Tyr Arg Leu Glu Pro His Glu
3140 3145 3150
Ala Ser Asn Gly Leu Asn Gly Leu Tyr Met Glu Thr Gly Leu Asn Ala
3155 3160 3165
Ser Asn Ile Leu Glu Thr Tyr Arg Ile Leu Glu Leu Tyr Ser Thr Tyr
3170 3175 3180
Arg Pro His Glu Ser Glu Arg Leu Tyr Ser Ala Leu Ala Ser Glu Arg
3185 3190 3195 3200
Met Glu Thr Gly Leu Tyr Gly Leu Thr His Arg Ala Leu Ala Pro Arg
3205 3210 3215
Ala Arg Gly Thr His Arg Ala Ser Asn Pro His Glu Ala Ser Asn Ala
3220 3225 3230
Ser Asn Ala Leu Ala Ala Leu Ala Ile Leu Glu Ala Ser Asn Thr Tyr
3235 3240 3245
Arg Gly Leu Asn Ala Ser Asn Leu Glu Thr Tyr Arg Leu Glu Gly Leu
3250 3255 3260
Tyr Leu Glu Ala Arg Gly Pro His Glu Ile Leu Glu Ile Leu Glu Leu
3265 3270 3275 3280
Tyr Ser Leu Tyr Ser Ala Leu Ala Ser Glu Arg Ala Ser Asn Ser Glu
3285 3290 3295
Arg Ala Arg Gly Ala Ser Asn Ile Leu Glu Ala Ser Asn Ala Ser Asn
3300 3305 3310
Ala Ser Pro Ala Ser Asn Ile Leu Glu Val Ala Leu Ala Arg Gly Gly
3315 3320 3325
Leu Gly Leu Tyr Ala Ser Pro Thr Tyr Arg Ile Leu Glu Thr Tyr Arg
3330 3335 3340
Leu Glu Ala Ser Asn Ile Leu Glu Ala Ser Pro Ala Ser Asn Ile Leu
3345 3350 3355 3360
Glu Ser Glu Arg Ala Ser Pro Gly Leu Ser Glu Arg Thr Tyr Arg Ala
3365 3370 3375
Arg Gly Val Ala Leu Thr Tyr Arg Val Ala Leu Leu Glu Val Ala Leu
3380 3385 3390
Ala Ser Asn Ser Glu Arg Leu Tyr Ser Gly Leu Ile Leu Glu Gly Leu
3395 3400 3405
Asn Thr His Arg Gly Leu Asn Leu Glu Pro His Glu Leu Glu Ala Leu
3410 3415 3420
Ala Pro Arg Ile Leu Glu Ala Ser Asn Ala Ser Pro Ala Ser Pro Pro
3425 3430 3435 3440
Arg Thr His Arg Pro His Glu Thr Tyr Arg Ala Ser Pro Val Ala Leu
3445 3450 3455
Leu Glu Gly Leu Asn Ile Leu Glu Leu Tyr Ser Leu Tyr Ser Thr Tyr
3460 3465 3470
Arg Thr Tyr Arg Gly Leu Leu Tyr Ser Thr His Arg Thr His Arg Thr
3475 3480 3485
Tyr Arg Ala Ser Asn Cys Tyr Ser Gly Leu Asn Ile Leu Glu Leu Glu
3490 3495 3500
Cys Tyr Ser Gly Leu Leu Tyr Ser Ala Ser Pro Thr His Arg Leu Tyr
3505 3510 3515 3520
Ser Thr His Arg Pro His Glu Gly Leu Tyr Leu Glu Pro His Glu Gly
3525 3530 3535
Leu Tyr Ile Leu Glu Gly Leu Tyr Leu Tyr Ser Pro His Glu Val Ala
3540 3545 3550
Leu Leu Tyr Ser Ala Ser Pro Thr Tyr Arg Gly Leu Tyr Thr Tyr Arg
3555 3560 3565
Val Ala Leu Thr Arg Pro Ala Ser Pro Thr His Arg Thr Tyr Arg Ala
3570 3575 3580
Ser Pro Ala Ser Asn Thr Tyr Arg Pro His Glu Cys Tyr Ser Ile Leu
3585 3590 3595 3600
Glu Ser Glu Arg Gly Leu Asn Thr Arg Pro Thr Tyr Arg Leu Glu Ala
3605 3610 3615
Arg Gly Ala Arg Gly Ile Leu Glu Ser Glu Arg Gly Leu Ala Ser Asn
3620 3625 3630
Ile Leu Glu Ala Ser Asn Leu Tyr Ser Leu Glu Ala Arg Gly Leu Glu
3635 3640 3645
Gly Leu Tyr Cys Tyr Ser Ala Ser Asn Thr Arg Pro Gly Leu Asn Pro
3650 3655 3660
His Glu Ile Leu Glu Pro Arg Val Ala Leu Ala Ser Pro Gly Leu Gly
3665 3670 3675 3680
Leu Tyr Thr Arg Pro Thr His Arg Gly Leu
3685 3690
<210> 15
<211> 4400
<212> DNA
<213> Clostridium botulinum
<400> 15
tagcattaaa aaaattagaa cctatagtaa ataaattaat taatatatag tttttataat 60
ttaattatga ataatattct taagataaaa agtaaatttt taaaaattta aattttcagt 120
ttacaaaaaa taacctgatt atgttatatg taattgtaaa aaacatataa aaaatcagaa 180
aaatttagga ggtatattat taatggatta aataataatt ttttaattta cttttgatta 240
ataaatatta aatgtttatt ttaattagga gatgatacgt atgccaataa ccataaataa 300
ttttagatat agtgatcctg ttaataatga tacaattatt atgatggagc caccatactg 360
taagggtcta gatatctatt ataaggcttt caaaataaca gatcgtattt ggatagtgcc 420
ggaaaggtat gaatttggga caaaacctga agattttaac ccaccatctt cattaataga 480
aggtgcatct gagtattacg atccaaatta tttaaggact gattctgata aagatagatt 540
tttacaaacc atggtaaaac tgtttaacag aattaaaaac aatgtagcag gtgaagcctt 600
attagataag ataataaatg ccatacctta ccttggaaat tcatattcct tactagacaa 660
gtttgataca aactctaatt cagtatcttt taatttatta gaacaagacc ccagtggagc 720
aactacaaaa tcagcaatgc tgacaaattt aataatattt ggacctgggc ctgttttaaa 780
taaaaatgag gttagaggta ttgtattgag ggtagataat aaaaattact tcccatgtag 840
agatggtttt ggctcaataa tgcaaatggc attttgccca gaatatgtac ctacctttga 900
taatgtaata gaaaatatta cgtcactcac tattggcaaa agcaaatatt ttcaagatcc 960
agcattacta ttaatgcacg aacttataca tgtactacat ggtttatacg gaatgcaggt 1020
atcaagccat gaaattattc catccaaaca agaaatttat atgcagcata catatccaat 1080
aagtgctgaa gaactattca cttttggcgg acaggatgct aatcttataa gtattgatat 1140
aaaaaacgat ttatatgaaa aaactttaaa tgattataaa gctatagcta acaaacttag 1200
tcaagtcact agctgcaatg atcccaacat tgatattgat agctacaaac aaatatatca 1260
acaaaaatat caattcgata aagatagcaa tggacaatat attgtaaatg aggataaatt 1320
tcagatacta tataatagca taatgtatgg ttttacagag attgaattgg gaaaaaaatt 1380
taatataaaa actagacttt cttattttag tatgaatcat gaccctgtaa aaattccaaa 1440
tttattagat gatacaattt acaatgatac agaaggattt aatatagaaa gcaaagatct 1500
gaaatctgaa tataaaggac aaaatatgag ggtaaataca aatgctttta gaaatgttga 1560
tggatcaggc ctagtttcaa aacttattgg cttatgtaaa aaaattatac caccaacaaa 1620
tataagagaa aatttatata atagaactgc atcattaaca gatttaggag gagaattatg 1680
tataaaaatt aaaaatgaag atttaacttt tatagctgaa aaaaatagct tttcagaaga 1740
accatttcaa gatgaaatag ttagttataa tacaaaaaat aaaccattaa attttaatta 1800
ttcgctagat aaaattattg tagattataa tctacaaagt aaaattacat tacctaatga 1860
taggacaacc ccagttacaa aaggaattcc atatgctcca gaatataaaa gtaatgctgc 1920
aagtacaata gaaatacata atattgatga caatacaata tatcaatatt tgtatgctca 1980
aaaatctcct acaactctac aaagaataac tatgactaat tctgttgatg acgcattaat 2040
aaattccacc aaaatatatt catattttcc atctgtaatc agtaaagtta accaaggtgc 2100
acaaggaatt ttattcttac agtgggtgag agatataatt gatgatttta ccaatgaatc 2160
ttcacaaaaa actactattg ataaaatttc agatgtatcc actattgttc cttatatagg 2220
acccgcatta aacattgtaa aacaaggcta tgagggaaac tttataggcg ctttagaaac 2280
taccggagtg gttttattat tagaatatat tccagaaatt actttaccag taattgcagc 2340
tttatctata gcagaaagta gcacacaaaa agaaaagata ataaaaacaa tagataactt 2400
tttagaaaaa agatatgaaa aatggattga agtatataaa ctagtaaaag caaaatggtt 2460
aggcacagtt aatacgcaat tccaaaaaag aagttatcaa atgtatagat ctttagaata 2520
tcaagtagat gcaataaaaa aaataataga ctatgaatat aaaatatatt caggacctga 2580
taaggaacaa attgccgacg aaattaataa tctgaaaaac aaacttgaag aaaaggctaa 2640
taaagcaatg ataaacataa atatatttat gagggaaagt tctagatcat ttttagttaa 2700
tcaaatgatt aacgaagcta aaaagcagtt attagagttt gatactcaaa gcaaaaatat 2760
tttaatgcag tatataaaag caaattctaa atttataggt ataactgaac taaaaaaatt 2820
agaatcaaaa ataaacaaag ttttttcaac accaattcca ttttcttatt ctaaaaatct 2880
ggattgttgg gttgataatg aagaagatat agatgttata ttaaaaaaga gtacaatttt 2940
aaatttagat attaataatg atattatatc agatatatct gggtttaatt catctgtaat 3000
aacatatcca gatgctcaat tggtgcccgg aataaatggc aaagcaatac atttagtaaa 3060
caatgaatct tctgaagtta tagtgcataa agctatggat attgaatata atgatatgtt 3120
taataatttt accgttagct tttggttgag ggttcctaaa gtatctgcta gtcatttaga 3180
acaatatggc acaaatgagt attcaataat tagctctatg aaaaaacata gtctatcaat 3240
aggatctggt tggagtgtat cacttaaagg taataactta atatggactt taaaagattc 3300
cgcgggagaa gttagacaaa taacttttag ggatttacct gataaattta atgcttattt 3360
agcaaataaa tgggttttta taactattac taatgataga ttatcttctg ctaatttgta 3420
tataaatgga gtacttatgg gaagtgcaga aattactggt ttaggagcta ttagagagga 3480
taataatata acattaaaac tagatagatg taataataat aatcaatacg tttctattga 3540
taaatttagg atattttgca aagcattaaa tccaaaagag attgaaaaat tatacacaag 3600
ttatttatct ataacctttt taagagactt ctggggaaac cctttacgat atgatacaga 3660
atattattta ataccagtag cttctagttc taaagatgtt caattgaaaa atataacaga 3720
ttatatgtat ttgacaaatg cgccatcgta tactaacgga aaattgaata tatattatag 3780
aaggttatat aatggactaa aatttattat aaaaagatat acacctaata atgaaataga 3840
ttcttttgtt aaatcaggtg attttattaa attatatgta tcatataaca ataatgagca 3900
cattgtaggt tatccgaaag atggaaatgc ctttaataat cttgatagaa ttctaagagt 3960
aggttataat gccccaggta tccctcttta taaaaaaatg gaagcagtaa aattgcgtga 4020
tttaaaaacc tattctgtac aacttaaatt atatgatgat aaaaatgcat ctttaggact 4080
agtaggtacc cataatggtc aaataggcaa cgatccaaat agggatatat taattgcaag 4140
caactggtac tttaatcatt taaaagataa aattttagga tgtgattggt actttgtacc 4200
tacagatgaa ggatggacaa atgattaaac agattgatat gttcatgatt actctatata 4260
aaaaattaaa taatataaca atctagctat attatttttg attattttct taatatatac 4320
taataaaata atcaaaatag agcctatctt aaattactga agggctgtgt caaaataaga 4380
ttttgacaca gcctctactt 4400
<210> 16
<211> 3708
<212> PRT
<213> Clostridium tetani
<400> 16
Met Glu Thr Pro Arg Ile Leu Glu Thr His Arg Ile Leu Glu Ala Ser
1 5 10 15
Asn Ala Ser Asn Pro His Glu Ala Arg Gly Thr Tyr Arg Ser Glu Arg
20 25 30
Ala Ser Pro Pro Arg Val Ala Leu Ala Ser Asn Ala Ser Asn Ala Ser
35 40 45
Pro Thr His Arg Ile Leu Glu Ile Leu Glu Met Glu Thr Met Glu Thr
50 55 60
Gly Leu Pro Arg Pro Arg Thr Tyr Arg Cys Tyr Ser Leu Tyr Ser Gly
65 70 75 80
Leu Tyr Leu Glu Ala Ser Pro Ile Leu Glu Thr Tyr Arg Thr Tyr Arg
85 90 95
Leu Tyr Ser Ala Leu Ala Pro His Glu Leu Tyr Ser Ile Leu Glu Thr
100 105 110
His Arg Ala Ser Pro Ala Arg Gly Ile Leu Glu Thr Arg Pro Ile Leu
115 120 125
Glu Val Ala Leu Pro Arg Gly Leu Ala Arg Gly Thr Tyr Arg Gly Leu
130 135 140
Pro His Glu Gly Leu Tyr Thr His Arg Leu Tyr Ser Pro Arg Gly Leu
145 150 155 160
Ala Ser Pro Pro His Glu Ala Ser Asn Pro Arg Pro Arg Ser Glu Arg
165 170 175
Ser Glu Arg Leu Glu Ile Leu Glu Gly Leu Gly Leu Tyr Ala Leu Ala
180 185 190
Ser Glu Arg Gly Leu Thr Tyr Arg Thr Tyr Arg Ala Ser Pro Pro Arg
195 200 205
Ala Ser Asn Thr Tyr Arg Leu Glu Ala Arg Gly Thr His Arg Ala Ser
210 215 220
Pro Ser Glu Arg Ala Ser Pro Leu Tyr Ser Ala Ser Pro Ala Arg Gly
225 230 235 240
Pro His Glu Leu Glu Gly Leu Asn Thr His Arg Met Glu Thr Val Ala
245 250 255
Leu Leu Tyr Ser Leu Glu Pro His Glu Ala Ser Asn Ala Arg Gly Ile
260 265 270
Leu Glu Leu Tyr Ser Ala Ser Asn Ala Ser Asn Val Ala Leu Ala Leu
275 280 285
Ala Gly Leu Tyr Gly Leu Ala Leu Ala Leu Glu Leu Glu Ala Ser Pro
290 295 300
Leu Tyr Ser Ile Leu Glu Ile Leu Glu Ala Ser Asn Ala Leu Ala Ile
305 310 315 320
Leu Glu Pro Arg Thr Tyr Arg Leu Glu Gly Leu Tyr Ala Ser Asn Ser
325 330 335
Glu Arg Thr Tyr Arg Ser Glu Arg Leu Glu Leu Glu Ala Ser Pro Leu
340 345 350
Tyr Ser Pro His Glu Ala Ser Pro Thr His Arg Ala Ser Asn Ser Glu
355 360 365
Arg Ala Ser Asn Ser Glu Arg Val Ala Leu Ser Glu Arg Pro His Glu
370 375 380
Ala Ser Asn Leu Glu Leu Glu Gly Leu Gly Leu Asn Ala Ser Pro Pro
385 390 395 400
Arg Ser Glu Arg Gly Leu Tyr Ala Leu Ala Thr His Arg Thr His Arg
405 410 415
Leu Tyr Ser Ser Glu Arg Ala Leu Ala Met Glu Thr Leu Glu Thr His
420 425 430
Arg Ala Ser Asn Leu Glu Ile Leu Glu Ile Leu Glu Pro His Glu Gly
435 440 445
Leu Tyr Pro Arg Gly Leu Tyr Pro Arg Val Ala Leu Leu Glu Ala Ser
450 455 460
Asn Leu Tyr Ser Ala Ser Asn Gly Leu Val Ala Leu Ala Arg Gly Gly
465 470 475 480
Leu Tyr Ile Leu Glu Val Ala Leu Leu Glu Ala Arg Gly Val Ala Leu
485 490 495
Ala Ser Pro Ala Ser Asn Leu Tyr Ser Ala Ser Asn Thr Tyr Arg Pro
500 505 510
His Glu Pro Arg Cys Tyr Ser Ala Arg Gly Ala Ser Pro Gly Leu Tyr
515 520 525
Pro His Glu Gly Leu Tyr Ser Glu Arg Ile Leu Glu Met Glu Thr Gly
530 535 540
Leu Asn Met Glu Thr Ala Leu Ala Pro His Glu Cys Tyr Ser Pro Arg
545 550 555 560
Gly Leu Thr Tyr Arg Val Ala Leu Pro Arg Thr His Arg Pro His Glu
565 570 575
Ala Ser Pro Ala Ser Asn Val Ala Leu Ile Leu Glu Gly Leu Ala Ser
580 585 590
Asn Ile Leu Glu Thr His Arg Ser Glu Arg Leu Glu Thr His Arg Ile
595 600 605
Leu Glu Gly Leu Tyr Leu Tyr Ser Ser Glu Arg Leu Tyr Ser Thr Tyr
610 615 620
Arg Pro His Glu Gly Leu Asn Ala Ser Pro Pro Arg Ala Leu Ala Leu
625 630 635 640
Glu Leu Glu Leu Glu Met Glu Thr His Ile Ser Gly Leu Leu Glu Ile
645 650 655
Leu Glu His Ile Ser Val Ala Leu Leu Glu His Ile Ser Gly Leu Tyr
660 665 670
Leu Glu Thr Tyr Arg Gly Leu Tyr Met Glu Thr Gly Leu Asn Val Ala
675 680 685
Leu Ser Glu Arg Ser Glu Arg His Ile Ser Gly Leu Ile Leu Glu Ile
690 695 700
Leu Glu Pro Arg Ser Glu Arg Leu Tyr Ser Gly Leu Asn Gly Leu Ile
705 710 715 720
Leu Glu Thr Tyr Arg Met Glu Thr Gly Leu Asn His Ile Ser Thr His
725 730 735
Arg Thr Tyr Arg Pro Arg Ile Leu Glu Ser Glu Arg Ala Leu Ala Gly
740 745 750
Leu Gly Leu Leu Glu Pro His Glu Thr His Arg Pro His Glu Gly Leu
755 760 765
Tyr Gly Leu Tyr Gly Leu Asn Ala Ser Pro Ala Leu Ala Ala Ser Asn
770 775 780
Leu Glu Ile Leu Glu Ser Glu Arg Ile Leu Glu Ala Ser Pro Ile Leu
785 790 795 800
Glu Leu Tyr Ser Ala Ser Asn Ala Ser Pro Leu Glu Thr Tyr Arg Gly
805 810 815
Leu Leu Tyr Ser Thr His Arg Leu Glu Ala Ser Asn Ala Ser Pro Thr
820 825 830
Tyr Arg Leu Tyr Ser Ala Leu Ala Ile Leu Glu Ala Leu Ala Ala Ser
835 840 845
Asn Leu Tyr Ser Leu Glu Ser Glu Arg Gly Leu Asn Val Ala Leu Thr
850 855 860
His Arg Ser Glu Arg Cys Tyr Ser Ala Ser Asn Ala Ser Pro Pro Arg
865 870 875 880
Ala Ser Asn Ile Leu Glu Ala Ser Pro Ile Leu Glu Ala Ser Pro Ser
885 890 895
Glu Arg Thr Tyr Arg Leu Tyr Ser Gly Leu Asn Ile Leu Glu Thr Tyr
900 905 910
Arg Gly Leu Asn Gly Leu Asn Leu Tyr Ser Thr Tyr Arg Gly Leu Asn
915 920 925
Pro His Glu Ala Ser Pro Leu Tyr Ser Ala Ser Pro Ser Glu Arg Ala
930 935 940
Ser Asn Gly Leu Tyr Gly Leu Asn Thr Tyr Arg Ile Leu Glu Val Ala
945 950 955 960
Leu Ala Ser Asn Gly Leu Ala Ser Pro Leu Tyr Ser Pro His Glu Gly
965 970 975
Leu Asn Ile Leu Glu Leu Glu Thr Tyr Arg Ala Ser Asn Ser Glu Arg
980 985 990
Ile Leu Glu Met Glu Thr Thr Tyr Arg Gly Leu Tyr Pro His Glu Thr
995 1000 1005
His Arg Gly Leu Ile Leu Glu Gly Leu Leu Glu Gly Leu Tyr Leu Tyr
1010 1015 1020
Ser Leu Tyr Ser Pro His Glu Ala Ser Asn Ile Leu Glu Leu Tyr Ser
1025 1030 1035 1040
Thr His Arg Ala Arg Gly Leu Glu Ser Glu Arg Thr Tyr Arg Pro His
1045 1050 1055
Glu Ser Glu Arg Met Glu Thr Ala Ser Asn His Ile Ser Ala Ser Pro
1060 1065 1070
Pro Arg Val Ala Leu Leu Tyr Ser Ile Leu Glu Pro Arg Ala Ser Asn
1075 1080 1085
Leu Glu Leu Glu Ala Ser Pro Ala Ser Pro Thr His Arg Ile Leu Glu
1090 1095 1100
Thr Tyr Arg Ala Ser Asn Ala Ser Pro Thr His Arg Gly Leu Gly Leu
1105 1110 1115 1120
Tyr Pro His Glu Ala Ser Asn Ile Leu Glu Gly Leu Ser Glu Arg Leu
1125 1130 1135
Tyr Ser Ala Ser Pro Leu Glu Leu Tyr Ser Ser Glu Arg Gly Leu Thr
1140 1145 1150
Tyr Arg Leu Tyr Ser Gly Leu Tyr Gly Leu Asn Ala Ser Asn Met Glu
1155 1160 1165
Thr Ala Arg Gly Val Ala Leu Ala Ser Asn Thr His Arg Ala Ser Asn
1170 1175 1180
Ala Leu Ala Pro His Glu Ala Arg Gly Ala Ser Asn Val Ala Leu Ala
1185 1190 1195 1200
Ser Pro Gly Leu Tyr Ser Glu Arg Gly Leu Tyr Leu Glu Val Ala Leu
1205 1210 1215
Ser Glu Arg Leu Tyr Ser Leu Glu Ile Leu Glu Gly Leu Tyr Leu Glu
1220 1225 1230
Cys Tyr Ser Leu Tyr Ser Leu Tyr Ser Ile Leu Glu Ile Leu Glu Pro
1235 1240 1245
Arg Pro Arg Thr His Arg Ala Ser Asn Ile Leu Glu Ala Arg Gly Gly
1250 1255 1260
Leu Ala Ser Asn Leu Glu Thr Tyr Arg Ala Ser Asn Ala Arg Gly Thr
1265 1270 1275 1280
His Arg Ala Leu Ala Ser Glu Arg Leu Glu Thr His Arg Ala Ser Pro
1285 1290 1295
Leu Glu Gly Leu Tyr Gly Leu Tyr Gly Leu Leu Glu Cys Tyr Ser Ile
1300 1305 1310
Leu Glu Leu Tyr Ser Ile Leu Glu Leu Tyr Ser Ala Ser Asn Gly Leu
1315 1320 1325
Ala Ser Pro Leu Glu Thr His Arg Pro His Glu Ile Leu Glu Ala Leu
1330 1335 1340
Ala Gly Leu Leu Tyr Ser Ala Ser Asn Ser Glu Arg Pro His Glu Ser
1345 1350 1355 1360
Glu Arg Gly Leu Gly Leu Pro Arg Pro His Glu Gly Leu Asn Ala Ser
1365 1370 1375
Pro Gly Leu Ile Leu Glu Val Ala Leu Ser Glu Arg Thr Tyr Arg Ala
1380 1385 1390
Ser Asn Thr His Arg Leu Tyr Ser Ala Ser Asn Leu Tyr Ser Pro Arg
1395 1400 1405
Leu Glu Ala Ser Asn Pro His Glu Ala Ser Asn Thr Tyr Arg Ser Glu
1410 1415 1420
Arg Leu Glu Ala Ser Pro Leu Tyr Ser Ile Leu Glu Ile Leu Glu Val
1425 1430 1435 1440
Ala Leu Ala Ser Pro Thr Tyr Arg Ala Ser Asn Leu Glu Gly Leu Asn
1445 1450 1455
Ser Glu Arg Leu Tyr Ser Ile Leu Glu Thr His Arg Leu Glu Pro Arg
1460 1465 1470
Ala Ser Asn Ala Ser Pro Ala Arg Gly Thr His Arg Thr His Arg Pro
1475 1480 1485
Arg Val Ala Leu Thr His Arg Leu Tyr Ser Gly Leu Tyr Ile Leu Glu
1490 1495 1500
Pro Arg Thr Tyr Arg Ala Leu Ala Pro Arg Gly Leu Thr Tyr Arg Leu
1505 1510 1515 1520
Tyr Ser Ser Glu Arg Ala Ser Asn Ala Leu Ala Ala Leu Ala Ser Glu
1525 1530 1535
Arg Thr His Arg Ile Leu Glu Gly Leu Ile Leu Glu His Ile Ser Ala
1540 1545 1550
Ser Asn Ile Leu Glu Ala Ser Pro Ala Ser Pro Ala Ser Asn Thr His
1555 1560 1565
Arg Ile Leu Glu Thr Tyr Arg Gly Leu Asn Thr Tyr Arg Leu Glu Thr
1570 1575 1580
Tyr Arg Ala Leu Ala Gly Leu Asn Leu Tyr Ser Ser Glu Arg Pro Arg
1585 1590 1595 1600
Thr His Arg Thr His Arg Leu Glu Gly Leu Asn Ala Arg Gly Ile Leu
1605 1610 1615
Glu Thr His Arg Met Glu Thr Thr His Arg Ala Ser Asn Ser Glu Arg
1620 1625 1630
Val Ala Leu Ala Ser Pro Ala Ser Pro Ala Leu Ala Leu Glu Ile Leu
1635 1640 1645
Glu Ala Ser Asn Ser Glu Arg Thr His Arg Leu Tyr Ser Ile Leu Glu
1650 1655 1660
Thr Tyr Arg Ser Glu Arg Thr Tyr Arg Pro His Glu Pro Arg Ser Glu
1665 1670 1675 1680
Arg Val Ala Leu Ile Leu Glu Ser Glu Arg Leu Tyr Ser Val Ala Leu
1685 1690 1695
Ala Ser Asn Gly Leu Asn Gly Leu Tyr Ala Leu Ala Gly Leu Asn Gly
1700 1705 1710
Leu Tyr Ile Leu Glu Leu Glu Pro His Glu Leu Glu Gly Leu Asn Thr
1715 1720 1725
Arg Pro Val Ala Leu Ala Arg Gly Ala Ser Pro Ile Leu Glu Ile Leu
1730 1735 1740
Glu Ala Ser Pro Ala Ser Pro Pro His Glu Thr His Arg Ala Ser Asn
1745 1750 1755 1760
Gly Leu Ser Glu Arg Ser Glu Arg Gly Leu Asn Leu Tyr Ser Thr His
1765 1770 1775
Arg Thr His Arg Ile Leu Glu Ala Ser Pro Leu Tyr Ser Ile Leu Glu
1780 1785 1790
Ser Glu Arg Ala Ser Pro Val Ala Leu Ser Glu Arg Thr His Arg Ile
1795 1800 1805
Leu Glu Val Ala Leu Pro Arg Thr Tyr Arg Ile Leu Glu Gly Leu Tyr
1810 1815 1820
Pro Arg Ala Leu Ala Leu Glu Ala Ser Asn Ile Leu Glu Val Ala Leu
1825 1830 1835 1840
Leu Tyr Ser Gly Leu Asn Gly Leu Tyr Thr Tyr Arg Gly Leu Gly Leu
1845 1850 1855
Tyr Ala Ser Asn Pro His Glu Ile Leu Glu Gly Leu Tyr Ala Leu Ala
1860 1865 1870
Leu Glu Gly Leu Thr His Arg Thr His Arg Gly Leu Tyr Val Ala Leu
1875 1880 1885
Val Ala Leu Leu Glu Leu Glu Leu Glu Gly Leu Thr Tyr Arg Ile Leu
1890 1895 1900
Glu Pro Arg Gly Leu Ile Leu Glu Thr His Arg Leu Glu Pro Arg Val
1905 1910 1915 1920
Ala Leu Ile Leu Glu Ala Leu Ala Ala Leu Ala Leu Glu Ser Glu Arg
1925 1930 1935
Ile Leu Glu Ala Leu Ala Gly Leu Ser Glu Arg Ser Glu Arg Thr His
1940 1945 1950
Arg Gly Leu Asn Leu Tyr Ser Gly Leu Leu Tyr Ser Ile Leu Glu Ile
1955 1960 1965
Leu Glu Leu Tyr Ser Thr His Arg Ile Leu Glu Ala Ser Pro Ala Ser
1970 1975 1980
Asn Pro His Glu Leu Glu Gly Leu Leu Tyr Ser Ala Arg Gly Thr Tyr
1985 1990 1995 2000
Arg Gly Leu Leu Tyr Ser Thr Arg Pro Ile Leu Glu Gly Leu Val Ala
2005 2010 2015
Leu Thr Tyr Arg Leu Tyr Ser Leu Glu Val Ala Leu Leu Tyr Ser Ala
2020 2025 2030
Leu Ala Leu Tyr Ser Thr Arg Pro Leu Glu Gly Leu Tyr Thr His Arg
2035 2040 2045
Val Ala Leu Ala Ser Asn Thr His Arg Gly Leu Asn Pro His Glu Gly
2050 2055 2060
Leu Asn Leu Tyr Ser Ala Arg Gly Ser Glu Arg Thr Tyr Arg Gly Leu
2065 2070 2075 2080
Asn Met Glu Thr Thr Tyr Arg Ala Arg Gly Ser Glu Arg Leu Glu Gly
2085 2090 2095
Leu Thr Tyr Arg Gly Leu Asn Val Ala Leu Ala Ser Pro Ala Leu Ala
2100 2105 2110
Ile Leu Glu Leu Tyr Ser Leu Tyr Ser Ile Leu Glu Ile Leu Glu Ala
2115 2120 2125
Ser Pro Thr Tyr Arg Gly Leu Thr Tyr Arg Leu Tyr Ser Ile Leu Glu
2130 2135 2140
Thr Tyr Arg Ser Glu Arg Gly Leu Tyr Pro Arg Ala Ser Pro Leu Tyr
2145 2150 2155 2160
Ser Gly Leu Gly Leu Asn Ile Leu Glu Ala Leu Ala Ala Ser Pro Gly
2165 2170 2175
Leu Ile Leu Glu Ala Ser Asn Ala Ser Asn Leu Glu Leu Tyr Ser Ala
2180 2185 2190
Ser Asn Leu Tyr Ser Leu Glu Gly Leu Gly Leu Leu Tyr Ser Ala Leu
2195 2200 2205
Ala Ala Ser Asn Leu Tyr Ser Ala Leu Ala Met Glu Thr Ile Leu Glu
2210 2215 2220
Ala Ser Asn Ile Leu Glu Ala Ser Asn Ile Leu Glu Pro His Glu Met
2225 2230 2235 2240
Glu Thr Ala Arg Gly Gly Leu Ser Glu Arg Ser Glu Arg Ala Arg Gly
2245 2250 2255
Ser Glu Arg Pro His Glu Leu Glu Val Ala Leu Ala Ser Asn Gly Leu
2260 2265 2270
Asn Met Glu Thr Ile Leu Glu Ala Ser Asn Gly Leu Ala Leu Ala Leu
2275 2280 2285
Tyr Ser Leu Tyr Ser Gly Leu Asn Leu Glu Leu Glu Gly Leu Pro His
2290 2295 2300
Glu Ala Ser Pro Thr His Arg Gly Leu Asn Ser Glu Arg Leu Tyr Ser
2305 2310 2315 2320
Ala Ser Asn Ile Leu Glu Leu Glu Met Glu Thr Gly Leu Asn Thr Tyr
2325 2330 2335
Arg Ile Leu Glu Leu Tyr Ser Ala Leu Ala Ala Ser Asn Ser Glu Arg
2340 2345 2350
Leu Tyr Ser Pro His Glu Ile Leu Glu Gly Leu Tyr Ile Leu Glu Thr
2355 2360 2365
His Arg Gly Leu Leu Glu Leu Tyr Ser Leu Tyr Ser Leu Glu Gly Leu
2370 2375 2380
Ser Glu Arg Leu Tyr Ser Ile Leu Glu Ala Ser Asn Leu Tyr Ser Val
2385 2390 2395 2400
Ala Leu Pro His Glu Ser Glu Arg Thr His Arg Pro Arg Ile Leu Glu
2405 2410 2415
Pro Arg Pro His Glu Ser Glu Arg Thr Tyr Arg Ser Glu Arg Leu Tyr
2420 2425 2430
Ser Ala Ser Asn Leu Glu Ala Ser Pro Cys Tyr Ser Thr Arg Pro Val
2435 2440 2445
Ala Leu Ala Ser Pro Ala Ser Asn Gly Leu Gly Leu Ala Ser Pro Ile
2450 2455 2460
Leu Glu Ala Ser Pro Val Ala Leu Ile Leu Glu Leu Glu Leu Tyr Ser
2465 2470 2475 2480
Leu Tyr Ser Ser Glu Arg Thr His Arg Ile Leu Glu Leu Glu Ala Ser
2485 2490 2495
Asn Leu Glu Ala Ser Pro Ile Leu Glu Ala Ser Asn Ala Ser Asn Ala
2500 2505 2510
Ser Pro Ile Leu Glu Ile Leu Glu Ser Glu Arg Ala Ser Pro Ile Leu
2515 2520 2525
Glu Ser Glu Arg Gly Leu Tyr Pro His Glu Ala Ser Asn Ser Glu Arg
2530 2535 2540
Ser Glu Arg Val Ala Leu Ile Leu Glu Thr His Arg Thr Tyr Arg Pro
2545 2550 2555 2560
Arg Ala Ser Pro Ala Leu Ala Gly Leu Asn Leu Glu Val Ala Leu Pro
2565 2570 2575
Arg Gly Leu Tyr Ile Leu Glu Ala Ser Asn Gly Leu Tyr Leu Tyr Ser
2580 2585 2590
Ala Leu Ala Ile Leu Glu His Ile Ser Leu Glu Val Ala Leu Ala Ser
2595 2600 2605
Asn Ala Ser Asn Gly Leu Ser Glu Arg Ser Glu Arg Gly Leu Val Ala
2610 2615 2620
Leu Ile Leu Glu Val Ala Leu His Ile Ser Leu Tyr Ser Ala Leu Ala
2625 2630 2635 2640
Met Glu Thr Ala Ser Pro Ile Leu Glu Gly Leu Thr Tyr Arg Ala Ser
2645 2650 2655
Asn Ala Ser Pro Met Glu Thr Pro His Glu Ala Ser Asn Ala Ser Asn
2660 2665 2670
Pro His Glu Thr His Arg Val Ala Leu Ser Glu Arg Pro His Glu Thr
2675 2680 2685
Arg Pro Leu Glu Ala Arg Gly Val Ala Leu Pro Arg Leu Tyr Ser Val
2690 2695 2700
Ala Leu Ser Glu Arg Ala Leu Ala Ser Glu Arg His Ile Ser Leu Glu
2705 2710 2715 2720
Gly Leu Gly Leu Asn Thr Tyr Arg Gly Leu Tyr Thr His Arg Ala Ser
2725 2730 2735
Asn Gly Leu Thr Tyr Arg Ser Glu Arg Ile Leu Glu Ile Leu Glu Ser
2740 2745 2750
Glu Arg Ser Glu Arg Met Glu Thr Leu Tyr Ser Leu Tyr Ser His Ile
2755 2760 2765
Ser Ser Glu Arg Leu Glu Ser Glu Arg Ile Leu Glu Gly Leu Tyr Ser
2770 2775 2780
Glu Arg Gly Leu Tyr Thr Arg Pro Ser Glu Arg Val Ala Leu Ser Glu
2785 2790 2795 2800
Arg Leu Glu Leu Tyr Ser Gly Leu Tyr Ala Ser Asn Ala Ser Asn Leu
2805 2810 2815
Glu Ile Leu Glu Thr Arg Pro Thr His Arg Leu Glu Leu Tyr Ser Ala
2820 2825 2830
Ser Pro Ser Glu Arg Ala Leu Ala Gly Leu Tyr Gly Leu Val Ala Leu
2835 2840 2845
Ala Arg Gly Gly Leu Asn Ile Leu Glu Thr His Arg Pro His Glu Ala
2850 2855 2860
Arg Gly Ala Ser Pro Leu Glu Pro Arg Ala Ser Pro Leu Tyr Ser Pro
2865 2870 2875 2880
His Glu Ala Ser Asn Ala Leu Ala Thr Tyr Arg Leu Glu Ala Leu Ala
2885 2890 2895
Ala Ser Asn Leu Tyr Ser Thr Arg Pro Val Ala Leu Pro His Glu Ile
2900 2905 2910
Leu Glu Thr His Arg Ile Leu Glu Thr His Arg Ala Ser Asn Ala Ser
2915 2920 2925
Pro Ala Arg Gly Leu Glu Ser Glu Arg Ser Glu Arg Ala Leu Ala Ala
2930 2935 2940
Ser Asn Leu Glu Thr Tyr Arg Ile Leu Glu Ala Ser Asn Gly Leu Tyr
2945 2950 2955 2960
Val Ala Leu Leu Glu Met Glu Thr Gly Leu Tyr Ser Glu Arg Ala Leu
2965 2970 2975
Ala Gly Leu Ile Leu Glu Thr His Arg Gly Leu Tyr Leu Glu Gly Leu
2980 2985 2990
Tyr Ala Leu Ala Ile Leu Glu Ala Arg Gly Gly Leu Ala Ser Pro Ala
2995 3000 3005
Ser Asn Ala Ser Asn Ile Leu Glu Thr His Arg Leu Glu Leu Tyr Ser
3010 3015 3020
Leu Glu Ala Ser Pro Ala Arg Gly Cys Tyr Ser Ala Ser Asn Ala Ser
3025 3030 3035 3040
Asn Ala Ser Asn Ala Ser Asn Gly Leu Asn Thr Tyr Arg Val Ala Leu
3045 3050 3055
Ser Glu Arg Ile Leu Glu Ala Ser Pro Leu Tyr Ser Pro His Glu Ala
3060 3065 3070
Arg Gly Ile Leu Glu Pro His Glu Cys Tyr Ser Leu Tyr Ser Ala Leu
3075 3080 3085
Ala Leu Glu Ala Ser Asn Pro Arg Leu Tyr Ser Gly Leu Ile Leu Glu
3090 3095 3100
Gly Leu Leu Tyr Ser Leu Glu Thr Tyr Arg Thr His Arg Ser Glu Arg
3105 3110 3115 3120
Thr Tyr Arg Leu Glu Ser Glu Arg Ile Leu Glu Thr His Arg Pro His
3125 3130 3135
Glu Leu Glu Ala Arg Gly Ala Ser Pro Pro His Glu Thr Arg Pro Gly
3140 3145 3150
Leu Tyr Ala Ser Asn Pro Arg Leu Glu Ala Arg Gly Thr Tyr Arg Ala
3155 3160 3165
Ser Pro Thr His Arg Gly Leu Thr Tyr Arg Thr Tyr Arg Leu Glu Ile
3170 3175 3180
Leu Glu Pro Arg Val Ala Leu Ala Leu Ala Ser Glu Arg Ser Glu Arg
3185 3190 3195 3200
Ser Glu Arg Leu Tyr Ser Ala Ser Pro Val Ala Leu Gly Leu Asn Leu
3205 3210 3215
Glu Leu Tyr Ser Ala Ser Asn Ile Leu Glu Thr His Arg Ala Ser Pro
3220 3225 3230
Thr Tyr Arg Met Glu Thr Thr Tyr Arg Leu Glu Thr His Arg Ala Ser
3235 3240 3245
Asn Ala Leu Ala Pro Arg Ser Glu Arg Thr Tyr Arg Thr His Arg Ala
3250 3255 3260
Ser Asn Gly Leu Tyr Leu Tyr Ser Leu Glu Ala Ser Asn Ile Leu Glu
3265 3270 3275 3280
Thr Tyr Arg Thr Tyr Arg Ala Arg Gly Ala Arg Gly Leu Glu Thr Tyr
3285 3290 3295
Arg Ala Ser Asn Gly Leu Tyr Leu Glu Leu Tyr Ser Pro His Glu Ile
3300 3305 3310
Leu Glu Ile Leu Glu Leu Tyr Ser Ala Arg Gly Thr Tyr Arg Thr His
3315 3320 3325
Arg Pro Arg Ala Ser Asn Ala Ser Asn Gly Leu Ile Leu Glu Ala Ser
3330 3335 3340
Pro Ser Glu Arg Pro His Glu Val Ala Leu Leu Tyr Ser Ser Glu Arg
3345 3350 3355 3360
Gly Leu Tyr Ala Ser Pro Pro His Glu Ile Leu Glu Leu Tyr Ser Leu
3365 3370 3375
Glu Thr Tyr Arg Val Ala Leu Ser Glu Arg Thr Tyr Arg Ala Ser Asn
3380 3385 3390
Ala Ser Asn Ala Ser Asn Gly Leu His Ile Ser Ile Leu Glu Val Ala
3395 3400 3405
Leu Gly Leu Tyr Thr Tyr Arg Pro Arg Leu Tyr Ser Ala Ser Pro Gly
3410 3415 3420
Leu Tyr Ala Ser Asn Ala Leu Ala Pro His Glu Ala Ser Asn Ala Ser
3425 3430 3435 3440
Asn Leu Glu Ala Ser Pro Ala Arg Gly Ile Leu Glu Leu Glu Ala Arg
3445 3450 3455
Gly Val Ala Leu Gly Leu Tyr Thr Tyr Arg Ala Ser Asn Ala Leu Ala
3460 3465 3470
Pro Arg Gly Leu Tyr Ile Leu Glu Pro Arg Leu Glu Thr Tyr Arg Leu
3475 3480 3485
Tyr Ser Leu Tyr Ser Met Glu Thr Gly Leu Ala Leu Ala Val Ala Leu
3490 3495 3500
Leu Tyr Ser Leu Glu Ala Arg Gly Ala Ser Pro Leu Glu Leu Tyr Ser
3505 3510 3515 3520
Thr His Arg Thr Tyr Arg Ser Glu Arg Val Ala Leu Gly Leu Asn Leu
3525 3530 3535
Glu Leu Tyr Ser Leu Glu Thr Tyr Arg Ala Ser Pro Ala Ser Pro Leu
3540 3545 3550
Tyr Ser Ala Ser Asn Ala Leu Ala Ser Glu Arg Leu Glu Gly Leu Tyr
3555 3560 3565
Leu Glu Val Ala Leu Gly Leu Tyr Thr His Arg His Ile Ser Ala Ser
3570 3575 3580
Asn Gly Leu Tyr Gly Leu Asn Ile Leu Glu Gly Leu Tyr Ala Ser Asn
3585 3590 3595 3600
Ala Ser Pro Pro Arg Ala Ser Asn Ala Arg Gly Ala Ser Pro Ile Leu
3605 3610 3615
Glu Leu Glu Ile Leu Glu Ala Leu Ala Ser Glu Arg Ala Ser Asn Thr
3620 3625 3630
Arg Pro Thr Tyr Arg Pro His Glu Ala Ser Asn His Ile Ser Leu Glu
3635 3640 3645
Leu Tyr Ser Ala Ser Pro Leu Tyr Ser Ile Leu Glu Leu Glu Gly Leu
3650 3655 3660
Tyr Cys Tyr Ser Ala Ser Pro Thr Arg Pro Thr Tyr Arg Pro His Glu
3665 3670 3675 3680
Val Ala Leu Pro Arg Thr His Arg Ala Ser Pro Gly Leu Gly Leu Tyr
3685 3690 3695
Thr Arg Pro Thr His Arg Ala Ser Asn Ala Ser Pro
3700 3705
<210> 17
<211> 31
<212> PRT
<213> Artificial Sequence
<220>
<223> cleavage site
<400> 17
Lys Leu Leu Cys Val Arg Gly Ile Ile Thr Ser Lys Thr Lys Ser Leu
1 5 10 15
Asp Lys Gly Tyr Asn Lys Ala Leu Asn Asp Leu Cys Ile Lys Val
20 25 30
<210> 18
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> cleavage site
<400> 18
Ile Gln Met Cys Lys Ser Val Lys Ala Pro Gly Ile Cys Ile Asp Val
1 5 10 15
<210> 19
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<223> cleavage site
<400> 19
Thr Lys Phe Cys His Lys Ala Ile Asp Gly Arg Ser Leu Tyr Asn Lys
1 5 10 15
Thr Leu Asp Cys Arg Glu Leu Leu Val
20 25
<210> 20
<211> 20
<212> PRT
<213> Artificial Sequence
<220>
<223> cleavage site
<400> 20
Thr Lys Val Cys Leu Arg Leu Thr Lys Asn Ser Arg Asp Asp Ser Thr
1 5 10 15
Cys Ile Lys Val
20
<210> 21
<211> 21
<212> PRT
<213> Artificial Sequence
<220>
<223> cleavage site
<400> 21
Ile Arg Phe Cys Lys Asn Ile Val Ser Val Lys Gly Ile Arg Lys Ser
1 5 10 15
Ile Cys Ile Glu Ile
20
<210> 22
<211> 23
<212> PRT
<213> Artificial Sequence
<220>
<223> cleavage site
<400> 22
Val Lys Phe Cys Lys Ser Val Ile Pro Arg Lys Gly Thr Lys Ala Pro
1 5 10 15
Pro Arg Leu Cys Ile Arg Val
20
<210> 23
<211> 21
<212> PRT
<213> Artificial Sequence
<220>
<223> cleavage site
<400> 23
Ile Ala Met Cys Lys Pro Val Met Tyr Lys Asn Thr Gly Lys Ser Glu
1 5 10 15
Gln Cys Ile Ile Val
20
<210> 24
<211> 35
<212> PRT
<213> Artificial Sequence
<220>
<223> cleavage site
<400> 24
Ile Gly Leu Cys Lys Lys Ile Ile Pro Pro Thr Asn Ile Arg Glu Asn
1 5 10 15
Leu Tyr Asn Arg Thr Ala Ser Leu Thr Asp Leu Gly Gly Glu Leu Cys
20 25 30
Ile Lys Ile
35
<210> 25
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<400> 25
Ala Leu Ala Pro Tyr Ile Pro
1 5
<210> 26
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<400> 26
Arg Phe Met Asp Tyr Trp Glu Gly Leu
1 5
<210> 27
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<220>
<221> MISC_FEATURE
<222> (2)..(4)
<223> Xaa can be any naturally occurring amino acid
<220>
<221> MISC_FEATURE
<222> (7)..(8)
<223> Xaa can be any naturally occurring amino acid
<400> 27
Phe Xaa Xaa Xaa Leu Trp Xaa Xaa Leu
1 5
<210> 28
<211> 14
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<400> 28
Glu Leu Glu Ser Pro Pro Pro Pro Tyr Ser Arg Tyr Pro Met
1 5 10
<210> 29
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<400> 29
Lys Val Gly Phe Phe Lys Arg
1 5
<210> 30
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<400> 30
Leu Leu Val Arg Gly Arg Thr Leu Val Val
1 5 10
<210> 31
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<400> 31
Asp Arg His Asp Ser Gly Leu Asp Ser Met
1 5 10
<210> 32
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<220>
<221> MISC_FEATURE
<222> (2)
<223> Xaa can be any naturally occurring amino acid
<220>
<221> MISC_FEATURE
<222> (4)
<223> Xaa can be any naturally occurring amino acid
<220>
<221> MISC_FEATURE
<222> (6)
<223> Xaa can be any naturally occurring amino acid
<400> 32
Pro Xaa Ala Xaa Val Xaa Pro
1 5
<210> 33
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<220>
<221> MISC_FEATURE
<222> (3)
<223> Xaa can be any naturally occurring amino acid
<220>
<221> MISC_FEATURE
<222> (5)..(6)
<223> Xaa can be any naturally occurring amino acid
<400> 33
Pro Pro Xaa Tyr Xaa Xaa Met
1 5
<210> 34
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> ligase recognition motif
<220>
<221> MISC_FEATURE
<222> (3)
<223> Xaa can be any naturally occurring amino acid
<220>
<221> MISC_FEATURE
<222> (5)
<223> Xaa can be any naturally occurring amino acid
<400> 34
Pro Pro Xaa Tyr Xaa
1 5
Claims (11)
- 피험자에서 감소된 기간의 근육 마비를 나타내는 보툴리눔 (Clostridium botulinum) 신경독 (BoNT/E) 폴리펩티드를 인코딩하는 변형 폴리뉴클레오티드로서, 상기 신경독 폴리펩티드는, SEQ ID NO: 9에 나타낸 뉴클레오티드로 이루어진 핵산 서열에 의해 인코딩되고, 신경독 폴리펩티드의 경쇄 내에 하나 이상의 분해 신호를 포함하며, 여기서 상기 신경독 폴리펩티드의 경쇄 내에 분해 신호는, 경쇄의 내부 또는 말단에 도입된 SEQ ID Nos.: 25-34에 나타낸 공통 서열을 갖는 E3 리가아제 인식 모티프인, 변형 폴리뉴클레오티드.
- 삭제
- 청구항 1에 있어서,
피험자에서 근육 마비의 기간은 4, 3 또는 2주 미만 동안 지속하는, 변형 폴리뉴클레오티드. - 삭제
- 청구항 1의 폴리뉴클레오티드를 포함하는 벡터.
- 청구항 1의 폴리뉴클레오티드를 포함하는 숙주 세포.
- 청구항 6에 있어서,
상기 세포는 E.coli 세포, 클로스트리디움 및 바실러스 세포부터 선택되는 숙주 세포. - 청구항 5의 벡터를 포함하는 숙주 세포.
- 청구항 8에 있어서,
상기 세포는 E.coli 세포, 클로스트리디움 및 바실러스 세포로부터 선택되는 숙주 세포. - a) 신경독 폴리펩티드를 발현시키는 조건하에서 청구항 6의 숙주 세포를 배양하는 단계; 및
b) 단계 a)의 배양된 숙주 세포로부터 신경독 폴리펩티드를 얻는 단계를 포함하는, 피험자에서 감소된 기간의 근육 마비를 나타내는 신경독 폴리펩티드의 제조방법. - 청구항 10에 있어서,
상기 방법은, 상기 신경독 폴리펩티드를 하나 이상의 약학적으로 허용가능한 담체를 포함하는 약제로서 제형화하는 단계를 더욱 포함하는, 신경독 폴리펩티드의 제조방법.
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US27019809P | 2009-07-02 | 2009-07-02 | |
EP09164365.0 | 2009-07-02 | ||
US61/270,198 | 2009-07-02 | ||
EP09164365 | 2009-07-02 | ||
PCT/EP2010/059398 WO2011000929A1 (en) | 2009-07-02 | 2010-07-01 | Neurotoxins exhibiting shortened biological activity |
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KR1020177003042A KR101818895B1 (ko) | 2009-07-02 | 2010-07-01 | 생물학적 활성이 감소된 신경독 |
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EP (1) | EP2449101B1 (ko) |
JP (2) | JP6059986B2 (ko) |
KR (2) | KR20120104140A (ko) |
CN (1) | CN102471765B9 (ko) |
AU (1) | AU2010267963B2 (ko) |
BR (1) | BRPI1014253A2 (ko) |
CA (1) | CA2763692A1 (ko) |
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HK (1) | HK1171246A1 (ko) |
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WO2011000929A1 (en) | 2011-01-06 |
KR20120104140A (ko) | 2012-09-20 |
BRPI1014253A2 (pt) | 2016-04-12 |
RU2012103376A (ru) | 2013-08-10 |
US20120107362A1 (en) | 2012-05-03 |
RU2582266C2 (ru) | 2016-04-20 |
AU2010267963A1 (en) | 2011-12-22 |
MX2011013014A (es) | 2012-01-27 |
US9193771B2 (en) | 2015-11-24 |
KR20170016529A (ko) | 2017-02-13 |
US20160030511A1 (en) | 2016-02-04 |
US20170072030A1 (en) | 2017-03-16 |
CN102471765B9 (zh) | 2016-07-27 |
US9827298B2 (en) | 2017-11-28 |
ES2693705T3 (es) | 2018-12-13 |
JP6059986B2 (ja) | 2017-01-11 |
HK1171246A1 (zh) | 2013-03-22 |
CA2763692A1 (en) | 2011-01-06 |
IL216414A (en) | 2016-08-31 |
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US8586329B2 (en) | 2013-11-19 |
US9511114B2 (en) | 2016-12-06 |
IL216414A0 (en) | 2012-02-29 |
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EP2449101B1 (en) | 2018-10-10 |
US20140045760A1 (en) | 2014-02-13 |
MX352265B (es) | 2017-11-16 |
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