DB code: M00185

CATH domain 3.90.1240.10 : Zincin-like Catalytic domain
-.-.-.- :
2.60.120.200 : Jelly Rolls
2.80.10.50 : Trefoil (Acidic Fibroblast Growth Factor, subunit A)
E.C. 3.4.24.68
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.60.120.200 : Jelly Rolls S00148 D00535 D00666 S00511 T00064 T00208
2.80.10.50 : Trefoil (Acidic Fibroblast Growth Factor, subunit A) D00169 D00666

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P04958 Tetanus toxin
EC 3.4.24.68
Tentoxylysin
Tetanus toxin light chain
(Tetanus toxin chain L)
Tetanus toxin heavy chain
(Tetanus toxin chain H)
NP_783831.1 (Protein)
NC_004565.1 (DNA/RNA sequence)
M27.001 (Metallo)
PF01742 (Peptidase_M27)
PF07951 (Toxin_R_bind_C)
PF07953 (Toxin_R_bind_N)
PF07952 (Toxin_trans)
[Graphical View]

KEGG enzyme name
tentoxilysin
tetanus neurotoxin

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P04958 TETX_CLOTE Hydrolysis of 76-Gln-|-Phe-77 bond in synaptobrevin 2. The precursor polypeptide is subsequently cleaved to yield subchains L and H. These remain linked by a disulfide bridge and are non-toxic after separation. Binds 1 zinc ion per subunit (By similarity).

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C99999 C00001 C00017 C00012
E.C.
Compound Zinc Synaptobrevin 2 H2O Protein Peptide
Type heavy metal peptide/protein H2O peptide/protein peptide/protein
ChEBI 29105
29105
15377
15377
PubChem 32051
32051
22247451
962
22247451
962
1yvgA Bound:_ZN Unbound Unbound Unbound
1z7hA Bound:_ZN Unbound Unbound Unbound
1a8dA01 Unbound Unbound Unbound Unbound
1af9A01 Unbound Unbound Unbound Unbound
1d0hA01 Unbound Unbound Unbound Unbound
1dfqA01 Unbound Unbound Unbound Unbound
1diwA01 Unbound Unbound Unbound Unbound
1dllA01 Unbound Unbound Unbound Unbound
1fv2A01 Unbound Unbound Unbound Unbound
1fv3A01 Unbound Unbound Unbound Unbound
1fv3B01 Unbound Unbound Unbound Unbound
1yxwA01 Unbound Unbound Unbound Unbound
1yynA01 Unbound Unbound Unbound Unbound
1a8dA02 Unbound Unbound Unbound Unbound
1af9A02 Unbound Unbound Unbound Unbound
1d0hA02 Unbound Unbound Unbound Unbound
1dfqA02 Unbound Unbound Unbound Unbound
1diwA02 Unbound Unbound Unbound Unbound
1dllA02 Unbound Unbound Unbound Unbound
1fv2A02 Unbound Unbound Unbound Unbound
1fv3A02 Unbound Unbound Unbound Unbound
1fv3B02 Unbound Unbound Unbound Unbound
1yxwA02 Unbound Unbound Unbound Unbound
1yynA02 Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P04958 & literature [6], [8], [32], [36], [38]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1yvgA GLU 233;GLU 270;ARG 371;TYR 374 HIS 232;HIS 236;GLU 270(Zinc binding)
1z7hA GLU 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
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 2207279
Journal Biophys Chem
Year 1990
Volume 36
Pages 155-66
Authors Singh BR, Fuller MP, Schiavo G
Title Molecular structure of tetanus neurotoxin as revealed by Fourier transform infrared and circular dichroic spectroscopy.
Related PDB
Related UniProtKB
[2]
Resource
Comments IDENTIFICATION AS ZINC-PROTEASE.
Medline ID 93010948
PubMed ID 1396558
Journal EMBO J
Year 1992
Volume 11
Pages 3577-83
Authors Schiavo G, Poulain B, Rossetto O, Benfenati F, Tauc L, Montecucco C
Title Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc.
Related PDB
Related UniProtKB P04958
[3]
Resource
Comments
Medline ID
PubMed ID 1331807
Journal Nature
Year 1992
Volume 359
Pages 832-5
Authors Schiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR, Montecucco C
Title Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8332193
Journal Nature
Year 1993
Volume 364
Pages 346-9
Authors McMahon HT, Ushkaryov YA, Edelmann L, Link E, Binz T, Niemann H, Jahn R, Sudhof TC
Title Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7901925
Journal Trends Biochem Sci
Year 1993
Volume 18
Pages 324-7
Authors Montecucco C, Schiavo G
Title Tetanus and botulism neurotoxins: a new group of zinc proteases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7911329
Journal Biochemistry
Year 1994
Volume 33
Pages 7014-20
Authors Li Y, Foran P, Fairweather NF, de Paiva A, Weller U, Dougan G, Dolly JO
Title A 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.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 7527117
Journal Mol Microbiol
Year 1994
Volume 13
Pages 1-8
Authors Montecucco C, Schiavo G
Title Mechanism of action of tetanus and botulinum neurotoxins.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8197120
Journal Proc Natl Acad Sci U S A
Year 1994
Volume 91
Pages 4688-92
Authors Yamasaki S, Hu Y, Binz T, Kalkuhl A, Kurazono H, Tamura T, Jahn R, Kandel E, Niemann H
Title Synaptobrevin/vesicle-associated membrane protein (VAMP) of Aplysia californica: structure and proteolysis by tetanus toxin and botulinal neurotoxins type D and F.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7731948
Journal Proteins
Year 1994
Volume 20
Pages 293-300
Authors Lebeda FJ, Olson MA
Title Secondary structural predictions for the clostridial neurotoxins.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 7801345
Journal Toxicon
Year 1994
Volume 32
Pages 1095-104
Authors Ledoux DN, Be XH, Singh BR
Title Quaternary structure of botulinum and tetanus neurotoxins as probed by chemical cross-linking and native gel electrophoresis.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 7744050
Journal Eur J Biochem
Year 1995
Volume 229
Pages 61-9
Authors De Filippis V, Vangelista L, Schiavo G, Tonello F, Montecucco C
Title Structural studies on the zinc-endopeptidase light chain of tetanus neurotoxin.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 7581298
Journal J Physiol Paris
Year 1995
Volume 89
Pages 43-50
Authors Rossetto O, Deloye F, Poulain B, Pellizzari R, Schiavo G, Montecucco C
Title The metallo-proteinase activity of tetanus and botulism neurotoxins.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8771234
Journal Q Rev Biophys
Year 1995
Volume 28
Pages 423-72
Authors Montecucco C, Schiavo G
Title Structure and function of tetanus and botulinum neurotoxins.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 8702770
Journal J Biol Chem
Year 1996
Volume 271
Pages 20353-8
Authors Pellizzari R, Rossetto O, Lozzi L, Giovedi' S, Johnson E, Shone CC, Montecucco C
Title Structural determinants of the specificity for synaptic vesicle-associated membrane protein/synaptobrevin of tetanus and botulinum type B and G neurotoxins.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9065770
Journal Biochem J
Year 1997
Volume 322
Pages 507-10
Authors Tonello F, Schiavo G, Montecucco C
Title Metal substitution of tetanus neurotoxin.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9013591
Journal J Biol Chem
Year 1997
Volume 272
Pages 3459-64
Authors Cornille F, Martin L, Lenoir C, Cussac D, Roques BP, Fournie-Zaluski MC
Title Cooperative exosite-dependent cleavage of synaptobrevin by tetanus toxin light chain.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 874-1314.
Medline ID 97475217
PubMed ID 9334741
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 788-92
Authors Umland TC, Wingert LM, Swaminathan S, Furey WF, Schmidt JJ, Sax M
Title Structure of the receptor binding fragment HC of tetanus neurotoxin.
Related PDB 1af9
Related UniProtKB P04958
[18]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID
Journal Am Cryst Assoc Abstr Papers
Year 1998
Volume 25
Pages 90
Authors Knapp M, Segelke B, Rupp B
Title The 1.61 Angstrom Structure of the Tetanus Toxin Ganglioside Binding Region: Solved by MAD and Mir Phase Combination.
Related PDB 1a8d
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9746536
Journal Biophys J
Year 1998
Volume 75
Pages 1953-63
Authors Meneghini C, Morante S
Title The active site structure of tetanus neurotoxin resolved by multiple scattering analysis in X-Ray absorption spectroscopy.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9914258
Journal Curr Opin Struct Biol
Year 1998
Volume 8
Pages 778-84
Authors Lacy DB, Stevens RC
Title Unraveling the structures and modes of action of bacterial toxins.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9719598
Journal J Med Chem
Year 1998
Volume 41
Pages 3450-60
Authors Martin L, Cornille F, Coric P, Roques BP, Fournie-Zaluski MC
Title Beta-amino-thiols inhibit the zinc metallopeptidase activity of tetanus toxin light chain.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 9783261
Journal J Nat Toxins
Year 1998
Volume 7
Pages 227-38
Authors Lebeda FJ, Olson MA
Title Predictions of secondary structure and solvent accessibility of the light chain of the clostridial neurotoxins.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 10413679
Journal J Cell Sci
Year 1999
Volume 112
Pages 2715-24
Authors Lalli G, Herreros J, Osborne SL, Montecucco C, Rossetto O, Schiavo G
Title Functional characterisation of tetanus and botulinum neurotoxins binding domains.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 9986722
Journal J Med Chem
Year 1999
Volume 42
Pages 515-25
Authors Martin L, Cornille F, Turcaud S, Meudal H, Roques BP, Fournie-Zaluski MC
Title Metallopeptidase inhibitors of tetanus toxin: A combinatorial approach.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 10518945
Journal J Mol Biol
Year 1999
Volume 291
Pages 1091-104
Authors Lacy DB, Stevens RC
Title Sequence homology and structural analysis of the clostridial neurotoxins.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10865130
Journal Biochimie
Year 2000
Volume 82
Pages 427-46
Authors Humeau Y, Doussau F, Grant NJ, Poulain B
Title How botulinum and tetanus neurotoxins block neurotransmitter release.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 11018534
Journal FEBS Lett
Year 2000
Volume 482
Pages 119-24
Authors Ginalski K, Venclovas C, Lesyng B, Fidelis K
Title Structure-based sequence alignment for the beta-trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site.
Related PDB
Related UniProtKB
[28]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 10722735
Journal J Biol Chem
Year 2000
Volume 275
Pages 8889-94
Authors Emsley P, Fotinou C, Black I, Fairweather NF, Charles IG, Watts C, Hewitt E, Isaacs NW
Title The structures of the H(C) fragment of tetanus toxin with carbohydrate subunit complexes provide insight into ganglioside binding.
Related PDB 1d0h 1dfq 1diw 1dll
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 11716521
Journal Biochem Biophys Res Commun
Year 2001
Volume 289
Pages 623-9
Authors Munro P, Kojima H, Dupont JL, Bossu JL, Poulain B, Boquet P
Title High sensitivity of mouse neuronal cells to tetanus toxin requires a GPI-anchored protein.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 11278003
Journal FEBS Lett
Year 2001
Volume 493
Pages 45-9
Authors Sutton JM, Chow-Worn O, Spaven L, Silman NJ, Hallis B, Shone CC
Title Tyrosine-1290 of tetanus neurotoxin plays a key role in its binding to gangliosides and functional binding to neurones.
Related PDB
Related UniProtKB
[31]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 11418600
Journal J Biol Chem
Year 2001
Volume 276
Pages 32274-81
Authors Fotinou C, Emsley P, Black I, Ando H, Ishida H, Kiso M, Sinha KA, Fairweather NF, Isaacs NW
Title The crystal structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue suggests cross-linking between ganglioside receptors and the toxin.
Related PDB 1fv2 1fv3
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 11306125
Journal Toxicon
Year 2001
Volume 39
Pages 1151-9
Authors Rossetto O, Caccin P, Rigoni M, Tonello F, Bortoletto N, Stevens RC, Montecucco C
Title Active-site mutagenesis of tetanus neurotoxin implicates TYR-375 and GLU-271 in metalloproteolytic activity.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 10936621
Journal Toxicon
Year 2001
Volume 39
Pages 27-41
Authors Rossetto O, Seveso M, Caccin P, Schiavo G, Montecucco C
Title Tetanus and botulinum neurotoxins: turning bad guys into good by research.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 12145198
Journal EMBO J
Year 2002
Volume 21
Pages 3970-9
Authors Quetglas S, Iborra C, Sasakawa N, De Haro L, Kumakura K, Sato K, Leveque C, Seagar M
Title Calmodulin and lipid binding to synaptobrevin regulates calcium-dependent exocytosis.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 12417130
Journal Trends Biochem Sci
Year 2002
Volume 27
Pages 552-8
Authors Turton K, Chaddock JA, Acharya KR
Title Botulinum and tetanus neurotoxins: structure, function and therapeutic utility.
Related PDB
Related UniProtKB
[36]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 15895988
Journal Biochemistry
Year 2005
Volume 44
Pages 7450-7
Authors Breidenbach MA, Brunger AT
Title 2.3 A crystal structure of tetanus neurotoxin light chain.
Related PDB 1z7h
Related UniProtKB
[37]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 16104015
Journal Proteins
Year 2005
Volume 61
Pages 288-95
Authors Jayaraman S, Eswaramoorthy S, Kumaran D, Swaminathan S
Title Common binding site for disialyllactose and tri-peptide in C-fragment of tetanus neurotoxin.
Related PDB 1yxw 1yyn
Related UniProtKB
[38]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 15904688
Journal Toxicon
Year 2005
Volume 45
Pages 929-39
Authors Rao KN, Kumaran D, Binz T, Swaminathan S
Title Structural analysis of the catalytic domain of tetanus neurotoxin.
Related PDB 1yvg
Related UniProtKB

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).

Created Updated
2005-12-13 2009-02-26