EzCatDB: S00529
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DB codeS00529
CATH domainDomain 13.40.710.10 : Beta-lactamaseCatalytic domain
E.C.3.4.16.4

CATH domainRelated DB codes (homologues)
3.40.710.10 : Beta-lactamaseS00512,S00513,S00414,T00222

Enzyme Name
UniProtKBKEGG

P39042
Protein nameD-alanyl-D-alanine carboxypeptidaseserine-type D-Ala-D-Ala carboxypeptidase
DD-peptidase
D-alanyl-D-alanine-carboxypeptidase
D-alanyl-D-alanine-cleaving-peptidase
D-alanyl-D-alanine-cleaving peptidase
DD-transpeptidase
D-alanine carboxypeptidase
DD-carboxypeptidase
D-alanyl carboxypeptidase
SynonymsDD-carboxypeptidase
DD-peptidase
EC 3.4.16.4
Penicillin-binding protein
PBP
MEROPSS11.004 (Serine)
PfamPF00768 (Peptidase_S11)
[Graphical view]


UniProtKB:Accession NumberP39042
Entry nameDACX_STRSK
ActivityPreferential cleavage: (Ac)(2)-L-Lys-D-Ala-|- D-Ala. Also transpeptidation of peptidyl-alanyl moieties that are N-acyl substituents of D-alanine.
Subunit
Subcellular locationSecreted (Potential).
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00012C00001C03326C00133C00012C02487
CompoundPeptideH2O(Ac)2-L-Lys-D-Ala-D-AlaD-AlaninePeptide(Ac)2-L-Lys-D-Ala
Typepeptide/proteinH2Oamino acids,amide group,carboxyl group,lipid,peptide/proteinamino acidspeptide/proteinamino acids,amide group,carboxyl group,peptide/protein,lipid,peptide/protein
ChEBI
15377
270
15570
57416

269
PubChem
962
22247451
152678
7311725
71080

5462243
              
1eqsAUnbound UnboundUnboundUnboundUnbound
1es2AUnbound UnboundUnboundUnboundUnbound
1es3AUnbound UnboundUnboundUnboundUnbound
1es4AUnbound UnboundUnboundUnboundUnbound
1es5AUnbound UnboundUnboundUnboundUnbound
1esiAUnbound UnboundUnboundUnboundUnbound
1j9mAUnbound UnboundUnboundUnboundUnbound
1skfAUnbound UnboundUnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1eqsASER 35;      ;SER  96
SER 35;SER 216
mutant K38H
1es2ASER 35;LYS 38;       
SER 35;SER 216
mutant S96A
1es3ASER 35;LYS 38;SER  96
SER 35;SER 216
mutant C98A
1es4ASER 35;LYS 38;SER  96
SER 35;SER 216
mutant C98N
1es5ASER 35;LYS 38;SER  96
       
mutant S216A
1esiASER 35;LYS 38;SER  96
SER 35;SER 216
mutant R248I
1j9mASER 35;      ;SER  96
SER 35;SER 216
mutant K38H
1skfASER 35;LYS 38;SER  96
SER 35;SER 216
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.21856-21858

references
[1]
CommentsX-ray crystallography (2.0 Angstroms)
PubMed ID10419503
JournalJ Biol Chem
Year1999
Volume274
Pages21853-60
AuthorsFonze E, Vermeire M, Nguyen-Disteche M, Brasseur R, Charlier P
TitleThe crystal structure of a penicilloyl-serine transferase of intermediate penicillin sensitivity. The DD-transpeptidase of streptomyces K15.
Related PDB1eqs,1es2,1es3,1es4,1es5,1esi,1skf
[2]
PubMed ID12627955
JournalBiochemistry
Year2003
Volume42
Pages2895-906
AuthorsRhazi N, Charlier P, Dehareng D, Engher D, Vermeire M, Frere JM, Nguyen-Disteche M, Fonze E
TitleCatalytic mechanism of the Streptomyces K15 DD-transpeptidase/penicillin-binding protein probed by site-directed mutagenesis and structural analysis.
Related PDB1j9m

comments
Theis enzyme belongs either to peptidase family-S11.
The enzyme can act as a bifunctional enzyme, catalyzing both hydrolysis and acyl group transfer reaction.
The hydrolysis involves two steps, acylation and deacylation. The acylation proceeds as follows:
(1) Despite no clear evidence, Lys38 has been implicated to act as a general base, which can activate the catalytic Ser35, according to the paper [2].
(2) The catalytic Ser35 acts as a nucleophile, which makes an attack on the carbonyl carbon atom to form an acyl-enzyme, accoriding to the literature [1], [2].
(3) An oxyanion hole, formed by mainchain amide groups of Ser35 and Ser216, stabilize the polarized carbonyl group of the substrate and tetrahedral intermediate during the transition state (see [2]).
(4) Lys38 acts as a general acid to protonate the leaving nitrogen, through the hydroxyl group of Ser96. (Ser96 acts as a proton shuttle.)
As for the deacylation, it has not been elucidated which residue can activate the hydrolytic water, which would attack the acyl-enzyme intermediate (see [2]). Probably, either Lys38 or Ser96 might play the role in activating the water (see [2]).

createdupdated
2002-09-272009-02-26


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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