EzCatDB: M00185
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DB codeM00185
CATH domainDomain 13.90.1240.10 : Zincin-likeCatalytic domain
Domain 2-.-.-.-
Domain 32.60.120.200 : Jelly Rolls
Domain 42.80.10.50 : Trefoil (Acidic Fibroblast Growth Factor, subunit A)
E.C.3.4.24.68

CATH domainRelated DB codes (homologues)
2.60.120.200 : Jelly RollsS00148,D00535,D00666,S00511,T00064,T00208
2.80.10.50 : Trefoil (Acidic Fibroblast Growth Factor, subunit A)D00169,D00666

Enzyme Name
UniProtKBKEGG

P04958
Protein nameTetanus toxintentoxilysin
tetanus neurotoxin
SynonymsEC 3.4.24.68
Tentoxylysin
ContainsTetanus toxin light chain
(Tetanus toxin chain L)
Tetanus toxin heavy chain
(Tetanus toxin chain H)
RefSeqNP_783831.1 (Protein)
NC_004565.1 (DNA/RNA sequence)
MEROPSM27.001 (Metallo)
PfamPF01742 (Peptidase_M27)
PF07951 (Toxin_R_bind_C)
PF07953 (Toxin_R_bind_N)
PF07952 (Toxin_trans)
[Graphical view]


UniProtKB:Accession NumberP04958
Entry nameTETX_CLOTE
ActivityHydrolysis of 76-Gln-|-Phe-77 bond in synaptobrevin 2.
SubunitThe precursor polypeptide is subsequently cleaved to yield subchains L and H. These remain linked by a disulfide bridge and are non-toxic after separation.
Subcellular location
CofactorBinds 1 zinc ion per subunit (By similarity).

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00038C99999C00001C00017C00012
CompoundZincSynaptobrevin 2H2OProteinPeptide
Typeheavy metalpeptide/proteinH2Opeptide/proteinpeptide/protein
ChEBI29105

15377


PubChem32051

962
22247451


             
1yvgABound:_ZNUnbound UnboundUnbound
1z7hABound:_ZNUnbound UnboundUnbound
1a8dA01UnboundUnbound UnboundUnbound
1af9A01UnboundUnbound UnboundUnbound
1d0hA01UnboundUnbound UnboundUnbound
1dfqA01UnboundUnbound UnboundUnbound
1diwA01UnboundUnbound UnboundUnbound
1dllA01UnboundUnbound UnboundUnbound
1fv2A01UnboundUnbound UnboundUnbound
1fv3A01UnboundUnbound UnboundUnbound
1fv3B01UnboundUnbound UnboundUnbound
1yxwA01UnboundUnbound UnboundUnbound
1yynA01UnboundUnbound UnboundUnbound
1a8dA02UnboundUnbound UnboundUnbound
1af9A02UnboundUnbound UnboundUnbound
1d0hA02UnboundUnbound UnboundUnbound
1dfqA02UnboundUnbound UnboundUnbound
1diwA02UnboundUnbound UnboundUnbound
1dllA02UnboundUnbound UnboundUnbound
1fv2A02UnboundUnbound UnboundUnbound
1fv3A02UnboundUnbound UnboundUnbound
1fv3B02UnboundUnbound UnboundUnbound
1yxwA02UnboundUnbound UnboundUnbound
1yynA02UnboundUnbound UnboundUnbound

Active-site residues
resource
Swiss-prot;P04958 & literature [6], [8], [32], [36], [38]
pdbCatalytic residuesCofactor-binding residues
          
1yvgAGLU 233;GLU 270;ARG 371;TYR 374
HIS 232;HIS 236;GLU 270(Zinc binding)
1z7hAGLU 234;GLU 271;ARG 372;TYR 375
HIS 233;HIS 237;GLU 271(Zinc binding)
1a8dA01 
 
1af9A01 
 
1d0hA01 
 
1dfqA01 
 
1diwA01 
 
1dllA01 
 
1fv2A01 
 
1fv3A01 
 
1fv3B01 
 
1yxwA01 
 
1yynA01 
 
1a8dA02 
 
1af9A02 
 
1d0hA02 
 
1dfqA02 
 
1diwA02 
 
1dllA02 
 
1fv2A02 
 
1fv3A02 
 
1fv3B02 
 
1yxwA02 
 
1yynA02 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]

[8]

[25]p.1098-1102
[32]

[35]p.555-556
[36]p.7454-7455
[38]p.932-936

references
[1]
PubMed ID2207279
JournalBiophys Chem
Year1990
Volume36
Pages155-66
AuthorsSingh BR, Fuller MP, Schiavo G
TitleMolecular structure of tetanus neurotoxin as revealed by Fourier transform infrared and circular dichroic spectroscopy.
[2]
CommentsIDENTIFICATION AS ZINC-PROTEASE.
Medline ID93010948
PubMed ID1396558
JournalEMBO J
Year1992
Volume11
Pages3577-83
AuthorsSchiavo G, Poulain B, Rossetto O, Benfenati F, Tauc L, Montecucco C
TitleTetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc.
Related UniProtKBP04958
[3]
PubMed ID1331807
JournalNature
Year1992
Volume359
Pages832-5
AuthorsSchiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR, Montecucco C
TitleTetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin.
[4]
PubMed ID8332193
JournalNature
Year1993
Volume364
Pages346-9
AuthorsMcMahon HT, Ushkaryov YA, Edelmann L, Link E, Binz T, Niemann H, Jahn R, Sudhof TC
TitleCellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein.
[5]
PubMed ID7901925
JournalTrends Biochem Sci
Year1993
Volume18
Pages324-7
AuthorsMontecucco C, Schiavo G
TitleTetanus and botulism neurotoxins: a new group of zinc proteases.
[6]
PubMed ID7911329
JournalBiochemistry
Year1994
Volume33
Pages7014-20
AuthorsLi Y, Foran P, Fairweather NF, de Paiva A, Weller U, Dougan G, Dolly JO
TitleA single mutation in the recombinant light chain of tetanus toxin abolishes its proteolytic activity and removes the toxicity seen after reconstitution with native heavy chain.
[7]
PubMed ID7527117
JournalMol Microbiol
Year1994
Volume13
Pages1-8
AuthorsMontecucco C, Schiavo G
TitleMechanism of action of tetanus and botulinum neurotoxins.
[8]
PubMed ID8197120
JournalProc Natl Acad Sci U S A
Year1994
Volume91
Pages4688-92
AuthorsYamasaki S, Hu Y, Binz T, Kalkuhl A, Kurazono H, Tamura T, Jahn R, Kandel E, Niemann H
TitleSynaptobrevin/vesicle-associated membrane protein (VAMP) of Aplysia californica: structure and proteolysis by tetanus toxin and botulinal neurotoxins type D and F.
[9]
PubMed ID7731948
JournalProteins
Year1994
Volume20
Pages293-300
AuthorsLebeda FJ, Olson MA
TitleSecondary structural predictions for the clostridial neurotoxins.
[10]
PubMed ID7801345
JournalToxicon
Year1994
Volume32
Pages1095-104
AuthorsLedoux DN, Be XH, Singh BR
TitleQuaternary structure of botulinum and tetanus neurotoxins as probed by chemical cross-linking and native gel electrophoresis.
[11]
PubMed ID7744050
JournalEur J Biochem
Year1995
Volume229
Pages61-9
AuthorsDe Filippis V, Vangelista L, Schiavo G, Tonello F, Montecucco C
TitleStructural studies on the zinc-endopeptidase light chain of tetanus neurotoxin.
[12]
PubMed ID7581298
JournalJ Physiol Paris
Year1995
Volume89
Pages43-50
AuthorsRossetto O, Deloye F, Poulain B, Pellizzari R, Schiavo G, Montecucco C
TitleThe metallo-proteinase activity of tetanus and botulism neurotoxins.
[13]
PubMed ID8771234
JournalQ Rev Biophys
Year1995
Volume28
Pages423-72
AuthorsMontecucco C, Schiavo G
TitleStructure and function of tetanus and botulinum neurotoxins.
[14]
PubMed ID8702770
JournalJ Biol Chem
Year1996
Volume271
Pages20353-8
AuthorsPellizzari R, Rossetto O, Lozzi L, Giovedi' S, Johnson E, Shone CC, Montecucco C
TitleStructural determinants of the specificity for synaptic vesicle-associated membrane protein/synaptobrevin of tetanus and botulinum type B and G neurotoxins.
[15]
PubMed ID9065770
JournalBiochem J
Year1997
Volume322
Pages507-10
AuthorsTonello F, Schiavo G, Montecucco C
TitleMetal substitution of tetanus neurotoxin.
[16]
PubMed ID9013591
JournalJ Biol Chem
Year1997
Volume272
Pages3459-64
AuthorsCornille F, Martin L, Lenoir C, Cussac D, Roques BP, Fournie-Zaluski MC
TitleCooperative exosite-dependent cleavage of synaptobrevin by tetanus toxin light chain.
[17]
CommentsX-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 874-1314.
Medline ID97475217
PubMed ID9334741
JournalNat Struct Biol
Year1997
Volume4
Pages788-92
AuthorsUmland TC, Wingert LM, Swaminathan S, Furey WF, Schmidt JJ, Sax M
TitleStructure of the receptor binding fragment HC of tetanus neurotoxin.
Related PDB1af9
Related UniProtKBP04958
[18]
CommentsX-ray crystallography
JournalAm Cryst Assoc Abstr Papers
Year1998
Volume25
Pages90
AuthorsKnapp M, Segelke B, Rupp B
TitleThe 1.61 Angstrom Structure of the Tetanus Toxin Ganglioside Binding Region: Solved by MAD and Mir Phase Combination.
Related PDB1a8d
[19]
PubMed ID9746536
JournalBiophys J
Year1998
Volume75
Pages1953-63
AuthorsMeneghini C, Morante S
TitleThe active site structure of tetanus neurotoxin resolved by multiple scattering analysis in X-Ray absorption spectroscopy.
[20]
PubMed ID9914258
JournalCurr Opin Struct Biol
Year1998
Volume8
Pages778-84
AuthorsLacy DB, Stevens RC
TitleUnraveling the structures and modes of action of bacterial toxins.
[21]
PubMed ID9719598
JournalJ Med Chem
Year1998
Volume41
Pages3450-60
AuthorsMartin L, Cornille F, Coric P, Roques BP, Fournie-Zaluski MC
TitleBeta-amino-thiols inhibit the zinc metallopeptidase activity of tetanus toxin light chain.
[22]
PubMed ID9783261
JournalJ Nat Toxins
Year1998
Volume7
Pages227-38
AuthorsLebeda FJ, Olson MA
TitlePredictions of secondary structure and solvent accessibility of the light chain of the clostridial neurotoxins.
[23]
PubMed ID10413679
JournalJ Cell Sci
Year1999
Volume112
Pages2715-24
AuthorsLalli G, Herreros J, Osborne SL, Montecucco C, Rossetto O, Schiavo G
TitleFunctional characterisation of tetanus and botulinum neurotoxins binding domains.
[24]
PubMed ID9986722
JournalJ Med Chem
Year1999
Volume42
Pages515-25
AuthorsMartin L, Cornille F, Turcaud S, Meudal H, Roques BP, Fournie-Zaluski MC
TitleMetallopeptidase inhibitors of tetanus toxin: A combinatorial approach.
[25]
PubMed ID10518945
JournalJ Mol Biol
Year1999
Volume291
Pages1091-104
AuthorsLacy DB, Stevens RC
TitleSequence homology and structural analysis of the clostridial neurotoxins.
[26]
PubMed ID10865130
JournalBiochimie
Year2000
Volume82
Pages427-46
AuthorsHumeau Y, Doussau F, Grant NJ, Poulain B
TitleHow botulinum and tetanus neurotoxins block neurotransmitter release.
[27]
PubMed ID11018534
JournalFEBS Lett
Year2000
Volume482
Pages119-24
AuthorsGinalski K, Venclovas C, Lesyng B, Fidelis K
TitleStructure-based sequence alignment for the beta-trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site.
[28]
CommentsX-ray Diffraction
PubMed ID10722735
JournalJ Biol Chem
Year2000
Volume275
Pages8889-94
AuthorsEmsley P, Fotinou C, Black I, Fairweather NF, Charles IG, Watts C, Hewitt E, Isaacs NW
TitleThe structures of the H(C) fragment of tetanus toxin with carbohydrate subunit complexes provide insight into ganglioside binding.
Related PDB1d0h,1dfq,1diw,1dll
[29]
PubMed ID11716521
JournalBiochem Biophys Res Commun
Year2001
Volume289
Pages623-9
AuthorsMunro P, Kojima H, Dupont JL, Bossu JL, Poulain B, Boquet P
TitleHigh sensitivity of mouse neuronal cells to tetanus toxin requires a GPI-anchored protein.
[30]
PubMed ID11278003
JournalFEBS Lett
Year2001
Volume493
Pages45-9
AuthorsSutton JM, Chow-Worn O, Spaven L, Silman NJ, Hallis B, Shone CC
TitleTyrosine-1290 of tetanus neurotoxin plays a key role in its binding to gangliosides and functional binding to neurones.
[31]
CommentsX-ray Diffraction
PubMed ID11418600
JournalJ Biol Chem
Year2001
Volume276
Pages32274-81
AuthorsFotinou C, Emsley P, Black I, Ando H, Ishida H, Kiso M, Sinha KA, Fairweather NF, Isaacs NW
TitleThe crystal structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue suggests cross-linking between ganglioside receptors and the toxin.
Related PDB1fv2,1fv3
[32]
PubMed ID11306125
JournalToxicon
Year2001
Volume39
Pages1151-9
AuthorsRossetto O, Caccin P, Rigoni M, Tonello F, Bortoletto N, Stevens RC, Montecucco C
TitleActive-site mutagenesis of tetanus neurotoxin implicates TYR-375 and GLU-271 in metalloproteolytic activity.
[33]
PubMed ID10936621
JournalToxicon
Year2001
Volume39
Pages27-41
AuthorsRossetto O, Seveso M, Caccin P, Schiavo G, Montecucco C
TitleTetanus and botulinum neurotoxins: turning bad guys into good by research.
[34]
PubMed ID12145198
JournalEMBO J
Year2002
Volume21
Pages3970-9
AuthorsQuetglas S, Iborra C, Sasakawa N, De Haro L, Kumakura K, Sato K, Leveque C, Seagar M
TitleCalmodulin and lipid binding to synaptobrevin regulates calcium-dependent exocytosis.
[35]
PubMed ID12417130
JournalTrends Biochem Sci
Year2002
Volume27
Pages552-8
AuthorsTurton K, Chaddock JA, Acharya KR
TitleBotulinum and tetanus neurotoxins: structure, function and therapeutic utility.
[36]
CommentsX-ray Diffraction
PubMed ID15895988
JournalBiochemistry
Year2005
Volume44
Pages7450-7
AuthorsBreidenbach MA, Brunger AT
Title2.3 A crystal structure of tetanus neurotoxin light chain.
Related PDB1z7h
[37]
CommentsX-ray Diffraction
PubMed ID16104015
JournalProteins
Year2005
Volume61
Pages288-95
AuthorsJayaraman S, Eswaramoorthy S, Kumaran D, Swaminathan S
TitleCommon binding site for disialyllactose and tri-peptide in C-fragment of tetanus neurotoxin.
Related PDB1yxw,1yyn
[38]
CommentsX-ray Diffraction
PubMed ID15904688
JournalToxicon
Year2005
Volume45
Pages929-39
AuthorsRao KN, Kumaran D, Binz T, Swaminathan S
TitleStructural analysis of the catalytic domain of tetanus neurotoxin.
Related PDB1yvg

comments
This enzyme belongs to the peptidase family-M27. This enzyme seems to be homologous to botulinum neurotoxin.
This enzyme is cleaved into two chains, light chain and heavy chain, which are covalently bonded through disulfide bond between cysteine residues.
The structure of the N-terminal domain of the heavy chain has not been solved yet. The light chain has a catalytic domain, whereas the C-terminal domains of the heavy chain contribute to receptor binding.
According to the literature [35], [36], the catalytic mechanism might be similar to that of thermolysin (E.C. 3.4.24.27, D00234 in EzCatDB).

createdupdated
2005-12-132009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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