Botulinum neurotoxin type A

Details

Name

Botulinum neurotoxin type A

Synonyms

• 3.4.24.69
• atx
• bna
• BoNT/A
• Bontoxilysin-A
• BOTOX

Gene Name

botA

Organism

Clostridium botulinum

Amino acid sequence

>lcl|BSEQ0017329|Botulinum neurotoxin type A
MPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN
PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG
STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY
GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN
RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA
KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV
LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT
GLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEE
ITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNG
KKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEA
AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG
AVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAK
VNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKA
MININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDK
VNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINI
GSKVNFDPIDKNQIQLFNLESSKIEVILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNN
EYTIINCMENNSGWKVSLNYGEIIWTLQDTQEIKQRVVFKYSQMINISDYINRWIFVTIT
NNRLNNSKIYINGRLIDQKPISNLGNIHASNNIMFKLDGCRDTHRYIWIKYFNLFDKELN
EKEIKDLYDNQSNSGILKDFWGDYLQYDKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPR
GSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQA
GVEKILSALEIPDVGNLSQVVVMKSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAK
LVASNWYNRQIERSSRTLGCSWEFIPVDDGWGERPL

Number of residues

1296

Molecular Weight

149452.615

Theoretical pI

Not Available

GO Classification

Functions

metalloendopeptidase activity / protein transmembrane transporter activity / zinc ion binding

Processes

inhibition of neurotransmitter uptake / pathogenesis / protein transmembrane transport

Components

extracellular region / host cell cytosol / host cell junction / host cell presynaptic membrane / integral component of membrane

General Function

Zinc ion binding

Specific Function

Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.

Pfam Domain Function

• Peptidase_M27 (PF01742)
• Toxin_R_bind_C (PF07951)
• Toxin_R_bind_N (PF07953)
• Toxin_trans (PF07952)

Transmembrane Regions

627-647 656-676

Cellular Location

Secreted

Chromosome Location

Not Available

Locus

Not Available

External Identifiers

Resource	Link
UniProtKB ID	P10845
UniProtKB Entry Name	BXA1_CLOBO

General References

1. Thompson DE, Brehm JK, Oultram JD, Swinfield TJ, Shone CC, Atkinson T, Melling J, Minton NP: The complete amino acid sequence of the Clostridium botulinum type A neurotoxin, deduced by nucleotide sequence analysis of the encoding gene. Eur J Biochem. 1990 Apr 20;189(1):73-81. [Article]
2. Binz T, Kurazono H, Wille M, Frevert J, Wernars K, Niemann H: The complete sequence of botulinum neurotoxin type A and comparison with other clostridial neurotoxins. J Biol Chem. 1990 Jun 5;265(16):9153-8. [Article]
3. East AK, Bhandari M, Stacey JM, Campbell KD, Collins MD: Organization and phylogenetic interrelationships of genes encoding components of the botulinum toxin complex in proteolytic Clostridium botulinum types A, B, and F: evidence of chimeric sequences in the gene encoding the nontoxic nonhemagglutinin component. Int J Syst Bacteriol. 1996 Oct;46(4):1105-12. [Article]
4. Fujita R, Fujinaga Y, Inoue K, Nakajima H, Kumon H, Oguma K: Molecular characterization of two forms of nontoxic-nonhemagglutinin components of Clostridium botulinum type A progenitor toxins. FEBS Lett. 1995 Nov 27;376(1-2):41-4. [Article]
5. Schmidt JJ, Sathyamoorthy V, DasGupta BR: Partial amino acid sequence of the heavy and light chains of botulinum neurotoxin type A. Biochem Biophys Res Commun. 1984 Mar 30;119(3):900-4. [Article]
6. DasGupta BR, Dekleva ML: Botulinum neurotoxin type A: sequence of amino acids at the N-terminus and around the nicking site. Biochimie. 1990 Sep;72(9):661-4. [Article]
7. Sathyamoorthy V, Dasgupta BR, Foley J, Niece RL: Botulinum neurotoxin type A: cleavage of the heavy chain into two halves and their partial sequences. Arch Biochem Biophys. 1988 Oct;266(1):142-51. [Article]
8. Shone CC, Hambleton P, Melling J: Inactivation of Clostridium botulinum type A neurotoxin by trypsin and purification of two tryptic fragments. Proteolytic action near the COOH-terminus of the heavy subunit destroys toxin-binding activity. Eur J Biochem. 1985 Aug 15;151(1):75-82. [Article]
9. Schiavo G, Santucci A, Dasgupta BR, Mehta PP, Jontes J, Benfenati F, Wilson MC, Montecucco C: Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds. FEBS Lett. 1993 Nov 29;335(1):99-103. [Article]
10. Rigoni M, Caccin P, Johnson EA, Montecucco C, Rossetto O: Site-directed mutagenesis identifies active-site residues of the light chain of botulinum neurotoxin type A. Biochem Biophys Res Commun. 2001 Nov 16;288(5):1231-7. [Article]
11. Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, Chapman ER: SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006 Apr 28;312(5773):592-6. Epub 2006 Mar 16. [Article]
12. Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC: Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat Struct Biol. 1998 Oct;5(10):898-902. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB07818	(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE	experimental	unknown		Details
DB07819	(2E)-3-(4-CHLOROPHENYL)-N-HYDROXYACRYLAMIDE	experimental	unknown		Details
DB13900	Equine Botulinum Neurotoxin A Immune FAB2	approved, experimental, investigational	yes	antibody	Details