DB code: S00399

RLCP classification 1.13.11400.460 : Hydrolysis
CATH domain 3.40.390.10 : Collagenase (Catalytic Domain) Catalytic domain
E.C. 3.4.24.46
CSA
M-CSA
MACiE

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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P34179 Zinc metalloproteinase adamalysin-2
EC 3.4.24.46
Adamalysin II
Proteinase II
M12.141 (Metallo)
PF01421 (Reprolysin)
[Graphical View]

KEGG enzyme name
adamalysin
Crotalus adamanteus metalloendopeptidase
proteinase I and II
Crotalus adamanteus venom proteinase II
adamalysin II

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P34179 VMAD2_CROAD Cleavage 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. Monomer. Secreted. Binds 1 calcium ion per subunit. Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00076 C00038 C00017 C00012 C00001 C00017 C00012
E.C.
Compound Calcium Zinc Protein Peptide H2O Protein Peptide
Type divalent metal (Ca2+, Mg2+) heavy metal peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 29108
29105
15377
PubChem 271
32051
962
22247451
1iagA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Bound:_ZN Unbound Unbound Unbound Unbound
2aigP Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Bound:_ZN Unbound Unbound Unbound Unbound
3aigA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Bound:_ZN Unbound Unbound Unbound Unbound
4aigA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Bound:_ZN Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P34179

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1iagA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 143 HIS 142;HIS 146;HIS 152(Zinc binding)
2aigP Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 143 HIS 142;HIS 146;HIS 152(Zinc binding)
3aigA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 143 HIS 142;HIS 146;HIS 152(Zinc binding)
4aigA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 143 HIS 142;HIS 146;HIS 152(Zinc binding)

References for Catalytic Mechanism
References Sections No. 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]
Resource
Comments X-ray crystallography (2.0 Angstroms)
Medline ID 94038897
PubMed ID 8223430
Journal EMBO J
Year 1993
Volume 12
Pages 4151-7
Authors Gomis-Ruth FX, Kress LF, Bode W
Title First structure of a snake venom metalloproteinase: a prototype for matrix metalloproteinases/collagenases.
Related PDB 1iag
Related UniProtKB P34179
[2]
Resource
Comments
Medline ID
PubMed ID 8243670
Journal FEBS Lett
Year 1993
Volume 335
Pages 76-80
Authors Grams F, Huber R, Kress LF, Moroder L, Bode W
Title Activation of snake venom metalloproteinases by a cysteine switch-like mechanism.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography (2.0 Angstroms)
Medline ID 94275840
PubMed ID 8006965
Journal J Mol Biol
Year 1994
Volume 239
Pages 513-44
Authors Gomis-Ruth FX, Kress LF, Kellermann J, Mayr I, Lee X, Huber R, Bode W
Title Refined 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 PDB
Related UniProtKB P34179
[4]
Resource
Comments
Medline ID
PubMed ID 7663339
Journal Protein Sci
Year 1995
Volume 4
Pages 823-40
Authors Stocker W, Grams F, Baumann U, Reinemer P, Gomis-Ruth FX, McKay DB, Bode W
Title The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8740360
Journal Structure
Year 1996
Volume 4
Pages 375-86
Authors Dhanaraj V, Ye QZ, Johnson LL, Hupe DJ, Ortwine DF, Dunbar JB Jr, Rubin JR, Pavlovsky A, Humblet C, Blundell TL
Title X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9034190
Journal Nature
Year 1997
Volume 385
Pages 729-33
Authors Black 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
Title A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-ray crystallography (2.0 Angstroms)
Medline ID 98089012
PubMed ID 9428736
Journal FEBS Lett
Year 1997
Volume 418
Pages 319-22
Authors Cirilli M, Gallina C, Gavuzzo E, Giordano C, Gomis-Ruth FX, Gorini B, Kress LF, Mazza F, Paradisi MP, Pochetti G, Politi V
Title 2 angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode.
Related PDB 4aig
Related UniProtKB P34179
[8]
Resource
Comments X-ray crystallography (2.8 Angstroms)
Medline ID 98180398
PubMed ID 9521103
Journal Protein Sci
Year 1998
Volume 7
Pages 283-92
Authors Gomis-Ruth FX, Meyer EF, Kress LF, Politi V
Title Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors.
Related PDB 2aig 3aig
Related UniProtKB P34179
[9]
Resource
Comments
Medline ID
PubMed ID 9784374
Journal J Mol Biol
Year 1998
Volume 283
Pages 657-68
Authors Gong W, Zhu X, Liu S, Teng M, Niu L
Title Crystal structures of acutolysin A, a three-disulfide hemorrhagic zinc metalloproteinase from the snake venom of Agkistrodon acutus.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10708855
Journal Biochim Biophys Acta
Year 2000
Volume 1477
Pages 146-56
Authors Matsui T, Fujimura Y, Titani K
Title Snake venom proteases affecting hemostasis and thrombosis.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12077431
Journal Acta Crystallogr D Biol Crystallogr
Year 2002
Volume 58
Pages 1118-28
Authors Huang KF, Chiou SH, Ko TP, Yuann JM, Wang AH
Title The 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.
Related PDB
Related UniProtKB

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].

Created Updated
2002-09-12 2009-02-26