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, |
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 is cleaved into two chains, The structure of the N-terminal domain of the heavy chain has not been solved yet. According to the literature [35], |
Created | Updated |
---|---|
2005-12-13 | 2009-02-26 |