EzCatDB: T00222

DB codeT00222
RLCP classification1.13.30015.15
CATH domainDomain 13.40.710.10Catalytic domain
Domain 22.40.128.50
Domain 32.40.128.50
E.C.3.4.11.19
CSA1ei5

CATH domainRelated DB codes (homologues)
3.40.710.10S00512,S00513,S00529,S00414

Enzyme Name
Swiss-protKEGG

Q9ZBA9
Protein nameD-aminopeptidaseD-stereospecific aminopeptidase
D-aminopeptidase
SynonymsEC 3.4.11.19


Swiss-prot:Accession NumberQ9ZBA9
Entry nameDAP_OCHAN
ActivityRelease 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.
SubunitHomodimer.
Subcellular location
Cofactor


SubstratesProductsintermediates
KEGG-idC00012C00001C00012C00405I00087I00085I00086
CompoundPeptideH2OPeptideD-Amino acidPeptidyl-tetrahedral intermediateAcyl-enzymeTetrahedral intermediate
Typepeptide/proteinH2Opeptide/proteinamino acids


1ei5A01Unbound
UnboundUnbound


1ei5A02Unbound
UnboundUnbound


1ei5A03Unbound
UnboundUnbound



Active-site residues
resource
literature [9]
pdbCatalytic residuesMain-chain involved in catalysis
1ei5A01SER 62;LYS 65;TYR 153;HIS 287
SER 62;ALA 290
1ei5A02

1ei5A03


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[9]p.976

references
[1]
PubMed ID2760064
JournalJ Biol Chem
Year1989
Volume264
Pages14233-9
AuthorsAsano Y, Nakazawa A, Kato Y, Kondo K
TitleProperties of a novel D-stereospecific aminopeptidase from Ochrobactrum anthropi.
[2]
JournalTetrahedron
Year1989
Volume45
Pages5743-5754
AuthorsKato Y, Asano Y, Nakazawa A, Kondo K
TitleFirst synthesis of D-amino acid N-alkyl amide catalyzed by D-aminopeptidase.
[3]
PubMed ID1540587
JournalBiochemistry
Year1992
Volume31
Pages2316-28
AuthorsAsano Y, Kato Y, Yamada A, Kondo K
TitleStructural similarity of D-aminopeptidase to carboxypeptidase DD and beta-lactamases.
Related Swiss-protQ9ZBA9
[4]
PubMed ID8439290
JournalBiochem J
Year1993
Volume290
Pages205-18
AuthorsRawlings ND, Barrett AJ
TitleEvolutionary families of peptidases.
[5]
JournalJ Ferment Bioeng
Year1995
Volume79
Pages614-616
AuthorsAsano Y, Yamaguchi K
TitleMutants of D-Aminopeptidase with Increased Thermal Stability
[6]
PubMed ID10379365
JournalCell Mol Life Sci
Year1999
Volume55
Pages812-8
AuthorsFanuel L, Thamm I, Kostanjevecki V, Samyn B, Joris B, Goffin C, Brannigan J, Van Beeumen J, Frere JM
TitleTwo new aminopeptidases from Ochrobactrum anthropi active on D-alanyl-p-nitroanilide.
[7]
PubMed ID16232749
JournalJ Biosci Bioeng
Year2000
Volume89
Pages295-306
AuthorsAsano Y, Lubbehusen TL
TitleEnzymes acting on peptides containing D-amino acid.
[8]
JournalJ Microbiol Biotechnol
Year2000
Volume10
Pages573-579
AuthorsAsano Y
TitleNew enzymes acting on peptides containing D-Amino acids: Their properties and application.
[9]
PubMed ID10986464
JournalStructure Fold Des
Year2000
Volume8
Pages971-80
AuthorsBompard-Gilles C, Remaut H, Villeret V, Prange T, Fanuel L, Delmarcelle M, Joris B, Frere J, Van Beeumen J
TitleCrystal structure of a D-aminopeptidase from Ochrobactrum anthropi, a new member of the 'penicillin-recognizing enzyme' family.
Related PDB1ei5
[10]
JournalJ Mol Catal, B Enzym
Year2001
Volume12
Pages53?59
AuthorsAsano Y, Umezaki M, Li Y-F, Tsubota S, Lubbehusen TL
TitleIsolation of microorganisms which utilize acidic d-amino acid oligomers.
[11]
PubMed ID15913357
JournalJ Am Chem Soc
Year2005
Volume127
Pages7696-7
AuthorsAsano Y, Yamaguchi S
TitleDynamic kinetic resolution of amino acid amide catalyzed by D-aminopeptidase and alpha-amino-epsilon-caprolactam racemase.
[12]
PubMed ID16131658
JournalProtein Sci
Year2005
Volume14
Pages2296-303
AuthorsDelmarcelle M, Boursoit MC, Filee P, Baurin SL, Frere JM, Joris B
TitleSpecificity inversion of Ochrobactrum anthropi D-aminopeptidase to a D,D-carboxypeptidase with new penicillin binding activity by directed mutagenesis.

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).

createdupdated
2006-01-242011-02-16


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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