DB code: D00191

RLCP classification 1.13.10880.280 : Hydrolysis
CATH domain 1.10.101.10 : Muramoyl-pentapeptide Carboxypeptidase; domain 1
3.30.1380.10 : Muramoyl-pentapeptide Carboxypeptidase; domain 2 Catalytic domain
E.C. 3.4.17.14
CSA 1lbu
M-CSA 1lbu
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P00733 Zinc D-Ala-D-Ala carboxypeptidase
EC 3.4.17.14
D-alanyl-D-alanine carboxypeptidase
Metallo DD-peptidase
Zn DD-peptidase
M15.001 (Metallo)
PF08291 (Peptidase_M15_3)
PF01471 (PG_binding_1)
[Graphical View]

KEGG enzyme name
zinc D-Ala-D-Ala carboxypeptidase
Zn2+ G peptidase, D-alanyl-D-alanine hydrolase
D-alanyl-D-alanine-cleaving carboxypeptidase
DD-carboxypeptidase
G enzyme
DD-carboxypeptidase-transpeptidase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00733 CBPM_STRAL Cleavage of the bond: (Ac)(2)-L-lysyl-D- alanyl-|-D-alanine. Secreted. Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C03326 C00001 C02487 C00133
E.C.
Compound Zinc (Ac)2-L-Lys-D-Ala-D-Ala H2O (Ac)2-L-Lys-D-Ala D-Alanine
Type heavy metal amino acids,amide group,carboxyl group,lipid,peptide/protein H2O amino acids,amide group,carboxyl group,peptide/protein,lipid,peptide/protein amino acids
ChEBI 29105
 29105
 		270
 270
 		15377
 15377
 		269
 269
 		15570
 57416
 15570
 57416
PubChem 32051
 32051
 		152678
 152678
 		22247451
 962
 22247451
 962
 		5462243
 5462243
 		71080
 7311725
 71080
 7311725
1lbuA01 Unbound Unbound Unbound Unbound
1lbuA02 Bound:_ZN Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00733 & literature [3], [9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1lbuA01
1lbuA02 TYR 189;HIS 192;ASP 194;HIS 195 HIS 154;ASP 161;HIS 197(Zinc binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
p.470
[8]
Fig.1, p.77-78
[9]
Fig.8, p.172-174

References
[1]
Resource
Comments
Medline ID
PubMed ID 7409166
Journal FEBS Lett
Year 1980
Volume 117
Pages 212-4
Authors Dideberg O, Charlier P, Dupont L, Vermeire M, Frere JM, Ghuysen JM
Title The 4.5 A resolution structure analysis of the exocellular DD-carboxypeptidase of Streptomyces albus G.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID
Journal FEBS LETTERS
Year 1980
Volume 117
Pages 215-218
Authors O. Dideberga, B. Jorisb, J. M. Frereb, J. M. Ghuysenb, G. Weberc, R. Robayec, J. M. Delbrouckc and I. Roelandtsd
Title The exocellular DD-carboxypeptidase of Streptomyces albus G: A metallo (Zn2+) enzyme
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 83012968
PubMed ID 7121588
Journal Nature
Year 1982
Volume 299
Pages 469-70
Authors Dideberg O, Charlier P, Dive G, Joris B, Frere JM, Ghuysen JM
Title Structure of a Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase at 2.5 A resolution.
Related PDB
Related UniProtKB P00733
[4]
Resource
Comments
Medline ID
PubMed ID 7123246
Journal Science
Year 1982
Volume 218
Pages 479-81
Authors Kelly JA, Moews PC, Knox JR, Frere JM, Ghuysen JM
Title Penicillin target enzyme and the antibiotic binding site.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 6743245
Journal Biochem J
Year 1984
Volume 219
Pages 763-72
Authors Charlier P, Dideberg O, Jamoulle JC, Frere JM, Ghuysen JM, Dive G, Lamotte-Brasseur J
Title Active-site-directed inactivators of the Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase of Streptomyces albus G.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11848831
Journal Chem Rev
Year 1996
Volume 96
Pages 2375-2434
Authors Lipscomb WN, Strater N
Title Recent Advances in Zinc Enzymology.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9614972
Journal Cell Mol Life Sci
Year 1998
Volume 54
Pages 353-8
Authors Kelly JA, Kuzin AP, Charlier P, Fonze E
Title X-ray studies of enzymes that interact with penicillins.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9702193
Journal Mol Cell
Year 1998
Volume 2
Pages 75-84
Authors Bussiere DE, Pratt SD, Katz L, Severin JM, Holzman T, Park CH
Title The structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID
PubMed ID
Journal Handbook of Metalloproteins
Year 2004
Volume 3
Pages 164-175
Authors Charlier, P., Wery, J.-P., Dideberg, O., Frere, J.-M
Title Streptomyces Albus G D-Ala-A-Ala Carboxypeptidase
Related PDB 1lbu
Related UniProtKB P00733

Comments
This enzyme belongs to the peptidase M15 family.
According to the literature [8] & [9], the reaction proceeds as follows:
(1) The carbonyl oxygen of substrate peptide bond is bound to zinc ion, whereas the catalytic water bound to the zinc is slightly shifted to His195.
(2) Asp194 modulates the activity of His195.
(3) His195 acts as a general base, to activate the catalytic water along with the zinc ion.
(4) The activated water makes a nucleophilic attack on the carbonyl carbon of the substrate, leading to the formation of tetrahedral oxyanion intermediate.
(5) The negative charge on the intermediate is stabilized by the sidechains of His192 and Tyr189 together with the zinc ion.
(6) His195 now acts as a general acid, to protonate the leaving amine group through a water.

Created Updated
2004-04-27 2009-02-26