DB code: T00222

RLCP classification 1.13.30015.15 : Hydrolysis
CATH domain 3.40.710.10 : Beta-lactamase Catalytic domain
2.40.128.50 : Lipocalin
2.40.128.50 : Lipocalin
E.C. 3.4.11.19
CSA 1ei5
M-CSA 1ei5
MACiE

CATH domain Related DB codes (homologues)
3.40.710.10 : Beta-lactamase S00512 S00513 S00529 S00414

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
Q9ZBA9 D-aminopeptidase
EC 3.4.11.19
S12.002 (Serine)
PF00144 (Beta-lactamase)
PF07930 (DAP_B)
PF07932 (DAP_C)
[Graphical View]

KEGG enzyme name
D-stereospecific aminopeptidase
D-aminopeptidase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9ZBA9 DAP_OCHAN Release of an N-terminal D-amino acid from a peptide, Xaa-|-Yaa-, in which Xaa is preferably D-Ala, D-Ser or D- Thr. D-amino acid amides and methyl esters also are hydrolyzed, as is glycine amide. Homodimer.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00001 C00012 C00405 I00087 I00085 I00086
E.C.
Compound Peptide H2O Peptide D-Amino acid Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein H2O peptide/protein amino acids
ChEBI 15377
PubChem 22247451
962
1ei5A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1ei5A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1ei5A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ei5A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 62;LYS 65;TYR 153;HIS 287 SER 62;ALA 290
1ei5A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ei5A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
p.976

References
[1]
Resource
Comments
Medline ID
PubMed ID 2760064
Journal J Biol Chem
Year 1989
Volume 264
Pages 14233-9
Authors Asano Y, Nakazawa A, Kato Y, Kondo K
Title Properties of a novel D-stereospecific aminopeptidase from Ochrobactrum anthropi.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID
Journal Tetrahedron
Year 1989
Volume 45
Pages 5743-5754
Authors Kato Y, Asano Y, Nakazawa A, Kondo K
Title First synthesis of D-amino acid N-alkyl amide catalyzed by D-aminopeptidase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1540587
Journal Biochemistry
Year 1992
Volume 31
Pages 2316-28
Authors Asano Y, Kato Y, Yamada A, Kondo K
Title Structural similarity of D-aminopeptidase to carboxypeptidase DD and beta-lactamases.
Related PDB
Related UniProtKB Q9ZBA9
[4]
Resource
Comments
Medline ID
PubMed ID 8439290
Journal Biochem J
Year 1993
Volume 290
Pages 205-18
Authors Rawlings ND, Barrett AJ
Title Evolutionary families of peptidases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID
Journal J Ferment Bioeng
Year 1995
Volume 79
Pages 614-616
Authors Asano Y, Yamaguchi K
Title Mutants of D-Aminopeptidase with Increased Thermal Stability
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10379365
Journal Cell Mol Life Sci
Year 1999
Volume 55
Pages 812-8
Authors Fanuel L, Thamm I, Kostanjevecki V, Samyn B, Joris B, Goffin C, Brannigan J, Van Beeumen J, Frere JM
Title Two new aminopeptidases from Ochrobactrum anthropi active on D-alanyl-p-nitroanilide.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 16232749
Journal J Biosci Bioeng
Year 2000
Volume 89
Pages 295-306
Authors Asano Y, Lubbehusen TL
Title Enzymes acting on peptides containing D-amino acid.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID
Journal J Microbiol Biotechnol
Year 2000
Volume 10
Pages 573-579
Authors Asano Y
Title New enzymes acting on peptides containing D-Amino acids: Their properties and application.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10986464
Journal Structure Fold Des
Year 2000
Volume 8
Pages 971-80
Authors Bompard-Gilles C, Remaut H, Villeret V, Prange T, Fanuel L, Delmarcelle M, Joris B, Frere J, Van Beeumen J
Title Crystal structure of a D-aminopeptidase from Ochrobactrum anthropi, a new member of the 'penicillin-recognizing enzyme' family.
Related PDB 1ei5
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID
Journal J Mol Catal, B Enzym
Year 2001
Volume 12
Pages 53?59
Authors Asano Y, Umezaki M, Li Y-F, Tsubota S, Lubbehusen TL
Title Isolation of microorganisms which utilize acidic d-amino acid oligomers.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 15913357
Journal J Am Chem Soc
Year 2005
Volume 127
Pages 7696-7
Authors Asano Y, Yamaguchi S
Title Dynamic kinetic resolution of amino acid amide catalyzed by D-aminopeptidase and alpha-amino-epsilon-caprolactam racemase.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 16131658
Journal Protein Sci
Year 2005
Volume 14
Pages 2296-303
Authors Delmarcelle M, Boursoit MC, Filee P, Baurin SL, Frere JM, Joris B
Title Specificity inversion of Ochrobactrum anthropi D-aminopeptidase to a D,D-carboxypeptidase with new penicillin binding activity by directed mutagenesis.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to peptidase family-S12.
This enzyme has got a similar active site to that of its homologous enzyme, DD-carboxypeptidase (S00414 in EzCatDB). Thus, the catalytic mechanism can be similar to that of the homologous enzyme.
According to the literature [9], the reaction of this enzyme probably proceeds as follows:
(1) The pKa of Lys65 must be lowered (or modulated) by Tyr153 and Asn155.
(2) Lys65 acts as a general base to activate Ser62.
(3) Ser62 makes a nucleophilic attack on the target bond, leading to formation of tetrahedral intermediate. The intermediate should be stabilized by the mainchain amide groups of Ser62 and Ala290.
(4) The second step involves the deacylation, which is the hydrolysis of the intermediate. According to the paper for its homologue (S00414 in EzCatDB), the phenoxide anion of Tyr153 would act as a general base, by activating a deacylating water for a nucleophile attack on the acyl-enzyme. Here, a positive charge on Lys65 would function as a modulator, by stabilzing the phenoxide anion on Tyr159, and by polarizing the ester bond for the nucleophilic attack by the water molecule (see S00414 in EzCatDB).

Created Updated
2006-01-24 2011-02-16