Target Information
Target General Information | Top | |||||
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Target ID |
T46616
(Former ID: TTDI01999)
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Target Name |
Bacterial Botulinum toxin A (Bact botA)
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Synonyms |
botA
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Gene Name |
Bact botA
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Acne vulgaris [ICD-11: ED80] | |||||
2 | Ataxic disorder [ICD-11: 8A03] | |||||
3 | Clostridium difficile enterocolitis [ICD-11: 1A04] | |||||
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.
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BioChemical Class |
Peptidase
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UniProt ID | ||||||
Sequence |
MPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN
PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT GLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEE ITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNG KKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAK VNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKA MININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDK VNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINI GSKVNFDPIDKNQIQLFNLESSKIEVILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNN EYTIINCMENNSGWKVSLNYGEIIWTLQDTQEIKQRVVFKYSQMINISDYINRWIFVTIT NNRLNNSKIYINGRLIDQKPISNLGNIHASNNIMFKLDGCRDTHRYIWIKYFNLFDKELN EKEIKDLYDNQSNSGILKDFWGDYLQYDKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPR GSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQA GVEKILSALEIPDVGNLSQVVVMKSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAK LVASNWYNRQIERSSRTLGCSWEFIPVDDGWGERPL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | RT-001 | Drug Info | Phase 2 | Acne vulgaris | [2] | |
2 | XOMA-3AB | Drug Info | Phase 1 | Clostridium infection | [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | RT-001 | Drug Info | [1] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: (3R)-3-(2,4-dichlorophenyl)-N~1~-hydroxy-N~5~-pentylpentanediamide | Ligand Info | |||||
Structure Description | Structure of the C. botulinum neurotoxin serotype A light chain protease in complex with noncovalent inhibitor 59 | PDB:6XCF | ||||
Method | X-ray diffraction | Resolution | 1.68 Å | Mutation | No | [5] |
PDB Sequence |
MQFVNKQFNY
10 KDPVNGVDIA20 YIKIPNVGQM30 QPVKAFKIHN40 KIWVIPERDT50 FTNPEEGDLN 60 PPPPVSYYDS75 TYLSTDNEKD85 NYLKGVTKLF95 ERIYSTDLGR105 MLLTSIVRGI 115 PFWGGSTIDT125 ELKVIDTNCI135 NVIQPDGSYR145 SEELNLVIIG155 PSADIIQFEC 165 KSFGHEVLNL175 TRNGYGSTQY185 IRFSPDFTFG195 FEESLEVDTN205 PLLGAGKFAT 215 DPAVTLAHEL225 IHAGHRLYGI235 AINPNRVFKV245 NTNAYYEMSG255 LEVSFEELRT 265 FGGHDAKFID275 SLQENEFRLY285 YYNKFKDIAS295 TLNKAKSIVG305 TTASLQYMKN 315 VFKEKYLLSE325 DTSGKFSVDK335 LKFDKLYKML345 TEIYTEDNFV355 KFFKVLNRKT 365 YLNFDKAVFK375 INIVPKVNYT385 IYDGFNLRNT395 NLAANFNGQN405 TEINNMNFTK 415 LKNFTGL
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Ligand Name: N-hydroxy-6-sulfanylhexanamide | Ligand Info | |||||
Structure Description | Structure of the C. botulinum neurotoxin serotype A light chain protease in complex with covalent inhibitor 20 | PDB:6XCB | ||||
Method | X-ray diffraction | Resolution | 1.74 Å | Mutation | No | [5] |
PDB Sequence |
QFVNKQFNYK
11 DPVNGVDIAY21 IKIPNVQMQP32 VKAFKIHNKI42 WVIPERDTFT52 NPEEGDLNPP 62 PEAKQVPVSY72 YDSTYLSTDN82 EKDNYLKGVT92 KLFERIYSTD102 LGRMLLTSIV 112 RGIPFWGGST122 IDTELKVIDT132 NCINVIQSYR145 SEELNLVIIG155 PSADIIQFEC 165 KSFGLNLTRN178 GYGSTQYIRF188 SPDFTFGFEE198 SLEVDTNPLL208 GAGKFATDPA 218 VTLAHELIHA228 GHRLYGIAIN238 PNRVFKVNTN248 AYYEMSGLEV258 SFEELRTFGG 268 HDAKFIDSLQ278 ENEFRLYYYN288 KFKDIASTLN298 KAKSIVGTTA308 SLQYMKNVFK 318 EKYLLSEDTS328 GKFSVDKLKF338 DKLYKMLTEI348 YTEDNFVKFF358 KVLNRKTYLN 368 FDKAVFKINI378 VPKVNYTIYD388 GFNLRNTNLA398 ANFNGQNTEI408 NNMNFTKLKN 418 FTGL
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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References | Top | |||||
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REF 1 | Clinical pipeline report, company report or official report of Revance Therapeutics. | |||||
REF 2 | ClinicalTrials.gov (NCT01124565) Safety Study of Two Repeat Doses of RT001 for the Treatment of Moderate to Severe Lateral Canthal Lines in Adults. U.S. National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT01357213) Phase 1 PK Study of XOMA 3AB. U.S. National Institutes of Health. | |||||
REF 4 | Clinical pipeline report, company report or official report of XOMA. | |||||
REF 5 | Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A. J Med Chem. 2020 Oct 8;63(19):11100-11120. |
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