EzCatDB: D00191
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DB codeD00191
RLCP classification1.13.10880.280 : Hydrolysis
CATH domainDomain 11.10.101.10 : Muramoyl-pentapeptide Carboxypeptidase; domain 1
Domain 23.30.1380.10 : Muramoyl-pentapeptide Carboxypeptidase; domain 2Catalytic domain
E.C.3.4.17.14
CSA1lbu


Enzyme Name
UniProtKBKEGG

P00733
Protein nameZinc D-Ala-D-Ala carboxypeptidasezinc 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
SynonymsEC 3.4.17.14
D-alanyl-D-alanine carboxypeptidase
Metallo DD-peptidase
Zn DD-peptidase
MEROPSM15.001 (Metallo)
PfamPF08291 (Peptidase_M15_3)
PF01471 (PG_binding_1)
[Graphical view]


UniProtKB:Accession NumberP00733
Entry nameCBPM_STRAL
ActivityCleavage of the bond: (Ac)(2)-L-lysyl-D- alanyl-|-D-alanine.
Subunit
Subcellular locationSecreted.
CofactorBinds 1 zinc ion per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00038C03326C00001C02487C00133
CompoundZinc(Ac)2-L-Lys-D-Ala-D-AlaH2O(Ac)2-L-Lys-D-AlaD-Alanine
Typeheavy metalamino acids,amide group,carboxyl group,lipid,peptide/proteinH2Oamino acids,amide group,carboxyl group,peptide/protein,lipid,peptide/proteinamino acids
ChEBI29105
270
15377
269
15570
57416
PubChem32051
152678
962
22247451
5462243
7311725
71080
             
1lbuA01UnboundUnbound UnboundUnbound
1lbuA02Bound:_ZNUnbound UnboundUnbound

Active-site residues
resource
Swiss-prot;P00733 & literature [3], [9]
pdbCatalytic residuesCofactor-binding residues
          
1lbuA01 
 
1lbuA02TYR 189;HIS 192;ASP 194;HIS 195
HIS 154;ASP 161;HIS 197(Zinc binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]p.470
[8]Fig.1, p.77-78
[9]Fig.8, p.172-174

references
[1]
PubMed ID7409166
JournalFEBS Lett
Year1980
Volume117
Pages212-4
AuthorsDideberg O, Charlier P, Dupont L, Vermeire M, Frere JM, Ghuysen JM
TitleThe 4.5 A resolution structure analysis of the exocellular DD-carboxypeptidase of Streptomyces albus G.
[2]
JournalFEBS LETTERS
Year1980
Volume117
Pages215-218
AuthorsO. Dideberga, B. Jorisb, J. M. Frereb, J. M. Ghuysenb, G. Weberc, R. Robayec, J. M. Delbrouckc and I. Roelandtsd
TitleThe exocellular DD-carboxypeptidase of Streptomyces albus G: A metallo (Zn2+) enzyme
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID83012968
PubMed ID7121588
JournalNature
Year1982
Volume299
Pages469-70
AuthorsDideberg O, Charlier P, Dive G, Joris B, Frere JM, Ghuysen JM
TitleStructure of a Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase at 2.5 A resolution.
Related UniProtKBP00733
[4]
PubMed ID7123246
JournalScience
Year1982
Volume218
Pages479-81
AuthorsKelly JA, Moews PC, Knox JR, Frere JM, Ghuysen JM
TitlePenicillin target enzyme and the antibiotic binding site.
[5]
PubMed ID6743245
JournalBiochem J
Year1984
Volume219
Pages763-72
AuthorsCharlier P, Dideberg O, Jamoulle JC, Frere JM, Ghuysen JM, Dive G, Lamotte-Brasseur J
TitleActive-site-directed inactivators of the Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase of Streptomyces albus G.
[6]
PubMed ID11848831
JournalChem Rev
Year1996
Volume96
Pages2375-2434
AuthorsLipscomb WN, Strater N
TitleRecent Advances in Zinc Enzymology.
[7]
PubMed ID9614972
JournalCell Mol Life Sci
Year1998
Volume54
Pages353-8
AuthorsKelly JA, Kuzin AP, Charlier P, Fonze E
TitleX-ray studies of enzymes that interact with penicillins.
[8]
PubMed ID9702193
JournalMol Cell
Year1998
Volume2
Pages75-84
AuthorsBussiere DE, Pratt SD, Katz L, Severin JM, Holzman T, Park CH
TitleThe structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
JournalHandbook of Metalloproteins
Year2004
Volume3
Pages164-175
AuthorsCharlier, P., Wery, J.-P., Dideberg, O., Frere, J.-M
TitleStreptomyces Albus G D-Ala-A-Ala Carboxypeptidase
Related PDB1lbu
Related UniProtKBP00733

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.

createdupdated
2004-04-272009-02-26


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