DB code: S00529

CATH domain 3.40.710.10 : Beta-lactamase Catalytic domain
E.C. 3.4.16.4
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.710.10 : Beta-lactamase S00512 S00513 S00414 T00222

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P39042 D-alanyl-D-alanine carboxypeptidase
DD-carboxypeptidase
DD-peptidase
EC 3.4.16.4
Penicillin-binding protein
PBP
S11.004 (Serine)
PF00768 (Peptidase_S11)
[Graphical View]

KEGG enzyme name
serine-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P39042 DACX_STRSK Preferential cleavage: (Ac)(2)-L-Lys-D-Ala-|- D-Ala. Also transpeptidation of peptidyl-alanyl moieties that are N-acyl substituents of D-alanine. Secreted (Potential).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00001 C03326 C00133 C00012 C02487
E.C.
Compound Peptide H2O (Ac)2-L-Lys-D-Ala-D-Ala D-Alanine Peptide (Ac)2-L-Lys-D-Ala
Type peptide/protein H2O amino acids,amide group,carboxyl group,lipid,peptide/protein amino acids peptide/protein amino acids,amide group,carboxyl group,peptide/protein,lipid,peptide/protein
ChEBI 15377
270
15570
57416
269
PubChem 22247451
962
152678
71080
7311725
5462243
1eqsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1es2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1es3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1es4A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1es5A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1esiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1j9mA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1skfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1eqsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 35; ;SER 96 SER 35;SER 216 mutant K38H
1es2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 35;LYS 38; SER 35;SER 216 mutant S96A
1es3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 35;LYS 38;SER 96 SER 35;SER 216 mutant C98A
1es4A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 35;LYS 38;SER 96 SER 35;SER 216 mutant C98N
1es5A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 35;LYS 38;SER 96 mutant S216A
1esiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 35;LYS 38;SER 96 SER 35;SER 216 mutant R248I
1j9mA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 35; ;SER 96 SER 35;SER 216 mutant K38H
1skfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 35;LYS 38;SER 96 SER 35;SER 216

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.21856-21858

References
[1]
Resource
Comments X-ray crystallography (2.0 Angstroms)
Medline ID
PubMed ID 10419503
Journal J Biol Chem
Year 1999
Volume 274
Pages 21853-60
Authors Fonze E, Vermeire M, Nguyen-Disteche M, Brasseur R, Charlier P
Title The crystal structure of a penicilloyl-serine transferase of intermediate penicillin sensitivity. The DD-transpeptidase of streptomyces K15.
Related PDB 1eqs 1es2 1es3 1es4 1es5 1esi 1skf
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 12627955
Journal Biochemistry
Year 2003
Volume 42
Pages 2895-906
Authors Rhazi N, Charlier P, Dehareng D, Engher D, Vermeire M, Frere JM, Nguyen-Disteche M, Fonze E
Title Catalytic mechanism of the Streptomyces K15 DD-transpeptidase/penicillin-binding protein probed by site-directed mutagenesis and structural analysis.
Related PDB 1j9m
Related UniProtKB

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]).

Created Updated
2002-09-27 2009-02-26