EzCatDB: S00399
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DB codeS00399
RLCP classification1.13.11400.460 : Hydrolysis
CATH domainDomain 13.40.390.10 : Collagenase (Catalytic Domain)Catalytic domain
E.C.3.4.24.46

CATH domainRelated DB codes (homologues)
3.40.390.10 : Collagenase (Catalytic Domain)S00394,S00395,S00397,S00398,D00232,D00236,M00101

Enzyme Name
UniProtKBKEGG

P34179
Protein nameZinc metalloproteinase adamalysin-2adamalysin
Crotalus adamanteus metalloendopeptidase
proteinase I and II
Crotalus adamanteus venom proteinase II
adamalysin II
SynonymsEC 3.4.24.46
Adamalysin II
Proteinase II
MEROPSM12.141 (Metallo)
PfamPF01421 (Reprolysin)
[Graphical view]


UniProtKB:Accession NumberP34179
Entry nameVMAD2_CROAD
ActivityCleavage of 1-Phe-|-Val-2, 5-His-|-Leu-6, 14- Ala-|-Leu-15, 15-Leu-|-Tyr-16, and 16-Tyr-|-Leu-17 of insulin B chain.
SubunitMonomer.
Subcellular locationSecreted.
CofactorBinds 1 calcium ion per subunit.,Binds 1 zinc ion per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00076C00038C00017C00012C00001C00017C00012
CompoundCalciumZincProteinPeptideH2OProteinPeptide
Typedivalent metal (Ca2+, Mg2+)heavy metalpeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein
ChEBI29108
29105


15377


PubChem271
32051


962
22247451


               
1iagABound:_CABound:_ZNUnboundUnbound UnboundUnbound
2aigPBound:_CABound:_ZNUnboundUnbound UnboundUnbound
3aigABound:_CABound:_ZNUnboundUnbound UnboundUnbound
4aigABound:_CABound:_ZNUnboundUnbound UnboundUnbound

Active-site residues
resource
Swiss-prot;P34179
pdbCatalytic residuesCofactor-binding residues
          
1iagAGLU 143
HIS 142;HIS 146;HIS 152(Zinc binding)
2aigPGLU 143
HIS 142;HIS 146;HIS 152(Zinc binding)
3aigAGLU 143
HIS 142;HIS 146;HIS 152(Zinc binding)
4aigAGLU 143
HIS 142;HIS 146;HIS 152(Zinc binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.4155
[3]p.530
[4]p.832
[5]p.381
[7]p.320-321
[8]p.285
[11]p.1122-1123

references
[1]
CommentsX-ray crystallography (2.0 Angstroms)
Medline ID94038897
PubMed ID8223430
JournalEMBO J
Year1993
Volume12
Pages4151-7
AuthorsGomis-Ruth FX, Kress LF, Bode W
TitleFirst structure of a snake venom metalloproteinase: a prototype for matrix metalloproteinases/collagenases.
Related PDB1iag
Related UniProtKBP34179
[2]
PubMed ID8243670
JournalFEBS Lett
Year1993
Volume335
Pages76-80
AuthorsGrams F, Huber R, Kress LF, Moroder L, Bode W
TitleActivation of snake venom metalloproteinases by a cysteine switch-like mechanism.
[3]
CommentsX-ray crystallography (2.0 Angstroms)
Medline ID94275840
PubMed ID8006965
JournalJ Mol Biol
Year1994
Volume239
Pages513-44
AuthorsGomis-Ruth FX, Kress LF, Kellermann J, Mayr I, Lee X, Huber R, Bode W
TitleRefined 2.0 A X-ray crystal structure of the snake venom zinc-endopeptidase adamalysin II. Primary and tertiary structure determination, refinement, molecular structure and comparison with astacin, collagenase and thermolysin.
Related UniProtKBP34179
[4]
PubMed ID7663339
JournalProtein Sci
Year1995
Volume4
Pages823-40
AuthorsStocker W, Grams F, Baumann U, Reinemer P, Gomis-Ruth FX, McKay DB, Bode W
TitleThe metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases.
[5]
PubMed ID8740360
JournalStructure
Year1996
Volume4
Pages375-86
AuthorsDhanaraj V, Ye QZ, Johnson LL, Hupe DJ, Ortwine DF, Dunbar JB Jr, Rubin JR, Pavlovsky A, Humblet C, Blundell TL
TitleX-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily.
[6]
PubMed ID9034190
JournalNature
Year1997
Volume385
Pages729-33
AuthorsBlack RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP
TitleA metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells.
[7]
CommentsX-ray crystallography (2.0 Angstroms)
Medline ID98089012
PubMed ID9428736
JournalFEBS Lett
Year1997
Volume418
Pages319-22
AuthorsCirilli M, Gallina C, Gavuzzo E, Giordano C, Gomis-Ruth FX, Gorini B, Kress LF, Mazza F, Paradisi MP, Pochetti G, Politi V
Title2 angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode.
Related PDB4aig
Related UniProtKBP34179
[8]
CommentsX-ray crystallography (2.8 Angstroms)
Medline ID98180398
PubMed ID9521103
JournalProtein Sci
Year1998
Volume7
Pages283-92
AuthorsGomis-Ruth FX, Meyer EF, Kress LF, Politi V
TitleStructures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors.
Related PDB2aig,3aig
Related UniProtKBP34179
[9]
PubMed ID9784374
JournalJ Mol Biol
Year1998
Volume283
Pages657-68
AuthorsGong W, Zhu X, Liu S, Teng M, Niu L
TitleCrystal structures of acutolysin A, a three-disulfide hemorrhagic zinc metalloproteinase from the snake venom of Agkistrodon acutus.
[10]
PubMed ID10708855
JournalBiochim Biophys Acta
Year2000
Volume1477
Pages146-56
AuthorsMatsui T, Fujimura Y, Titani K
TitleSnake venom proteases affecting hemostasis and thrombosis.
[11]
PubMed ID12077431
JournalActa Crystallogr D Biol Crystallogr
Year2002
Volume58
Pages1118-28
AuthorsHuang KF, Chiou SH, Ko TP, Yuann JM, Wang AH
TitleThe 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium.

comments
This enzyme belongs to the peptidase family-M12B.
According to the papers [1], [3], & [7], zinc ion and carboxylate of Glu143 are proposed to polarize the zinc-bound water molecule for the nucleophilic attack on the scissile peptide bond during the catalysis.
According to the literature [11], the pKa value of zinc-bound water in the homologous enzyme, carboxypeptidase A, lowered so as to play a functional role in the catalysis. In the homologous enzyme, the catalysis seems to proceed through the reaction in which the carboxylic group of the catalytic glutamate (corresponding to Glu143) acts as a general base to promote the nucleophilic attack by a water on the carbonyl group of scissile peptide bond. The stabilized tetrahedral intermediate then collapses with a requisite proton donation from the protonated glutamate (corresponding to Glu143) [11].

createdupdated
2002-09-122009-02-26


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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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