Reference : Crystal structure of a D-aminopeptidase from Ochrobactrum anthropi, a new member of t...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Crystal structure of a D-aminopeptidase from Ochrobactrum anthropi, a new member of the 'penicillin-recognizing enzyme' family.
Bompard-Gilles, C. [> > > >]
Remaut, H. [> > > >]
Villeret, V. [> > > >]
Prange, T. [> > > >]
Fanuel, L. [> > > >]
Delmarcelle, Michaël mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Joris, Bernard mailto [Université de Liège - ULg > Département des sciences de la vie > Physiologie et génétique bactériennes - Centre d'ingénierie des protéines >]
Frère, Jean-Marie mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Van Beeumen, J. [> > > >]
Cell Press
Yes (verified by ORBi)
[en] Amino Acid Sequence ; Aminopeptidases/chemistry ; Bacillus/enzymology ; Bacterial Proteins ; Binding Sites ; Carboxypeptidases/chemistry ; Carrier Proteins/chemistry ; Crystallography, X-Ray ; Dimerization ; Hexosyltransferases ; Models, Molecular ; Molecular Sequence Data ; Muramoylpentapeptide Carboxypeptidase/chemistry ; Ochrobactrum anthropi/enzymology ; Penicillin-Binding Proteins ; Peptidyl Transferases ; Protein Structure, Secondary ; Streptomyces/enzymology ; beta-Lactamases/chemistry
[en] 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.

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