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http://purl.uniprot.org/citations/10986464http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10986464http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10986464http://www.w3.org/2000/01/rdf-schema#comment"

Background

beta-Lactam compounds are the most widely used antibiotics. They inactivate bacterial DD-transpeptidases, also called penicillin-binding proteins (PBPs), involved in cell-wall biosynthesis. The most common bacterial resistance mechanism against beta-lactam compounds is the synthesis of beta-lactamases that hydrolyse beta-lactam rings. These enzymes are believed to have evolved from cell-wall DD-peptidases. Understanding the biochemical and mechanistic features of the beta-lactam targets is crucial because of the increasing number of resistant bacteria. DAP is a D-aminopeptidase produced by Ochrobactrum anthropi. It is inhibited by various beta-lactam compounds and shares approximately 25% sequence identity with the R61 DD-carboxypeptidase and the class C beta-lactamases.

Results

The crystal structure of DAP has been determined to 1.9 A resolution using the multiple isomorphous replacement (MIR) method. The enzyme folds into three domains, A, B and C. Domain A, which contains conserved catalytic residues, has the classical fold of serine beta-lactamases, whereas domains B and C are both antiparallel eight-stranded beta barrels. A loop of domain C protrudes into the substrate-binding site of the enzyme.

Conclusions

Comparison of the biochemical properties and the structure of DAP with PBPs and serine beta-lactamases shows that although the catalytic site of the enzyme is very similar to that of beta-lactamases, its substrate and inhibitor specificity rests on residues of domain C. DAP is a new member of the family of penicillin-recognizing proteins (PRPs) and, at the present time, its enzymatic specificity is clearly unique."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(00)00188-x"xsd:string
http://purl.uniprot.org/citations/10986464http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(00)00188-x"xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Joris B."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Joris B."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Prange T."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Prange T."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Van Beeumen J."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Van Beeumen J."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Frere J.-M."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Frere J.-M."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Villeret V."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Villeret V."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Bompard-Gilles C."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Bompard-Gilles C."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Delmarcelle M."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Delmarcelle M."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Fanuel L."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Fanuel L."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Remaut H."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/author"Remaut H."xsd:string
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/10986464http://purl.uniprot.org/core/date"2000"xsd:gYear
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