The 2.4-A crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin. (original) (raw)

Article (Scientific journals)

The 2.4-A crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin.

; Kerff, Frédéric; Fonze, E. et al.

2002 • In Cellular and Molecular Life Sciences, 59 (7), p. 1223-32

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Keywords :

Amino Acid Sequence; Bacterial Proteins; Binding Sites; Carrier Proteins/chemistry/genetics/metabolism; Crystallography, X-Ray; Enterococcus faecium/drug effects; Hexosyltransferases; Macromolecular Substances; Models, Molecular; Molecular Sequence Data; Muramoylpentapeptide Carboxypeptidase/chemistry/genetics/metabolism; Mutation; Penicillin G/chemistry/metabolism; Penicillin Resistance; Penicillin-Binding Proteins; Penicillins/chemistry/metabolism; Peptidyl Transferases; Protein Binding; Protein Structure, Tertiary; Sequence Alignment

Abstract :

[en] Penicillin-binding proteins (PBPs) are membrane proteins involved in the final stages of peptidoglycan synthesis and represent the targets of beta-lactam antibiotics. Enterococci are naturally resistant to these antibiotics because they produce a PBP, named PBP5fm in Enterococcus faecium, with low-level affinity for beta-lactams. We report here the crystal structure of the acyl-enzyme complex of PBP5fm with benzylpenicillin at a resolution of 2.4 A. A characteristic of the active site, which distinguishes PBP5fm from other PBPs of known structure, is the topology of the loop 451-465 defining the left edge of the cavity. The residue Arg464, involved in a salt bridge with the residue Asp481, confers a greater rigidity to the PBP5fm active site. In addition, the presence of the Val465 residue, which points into the active site, reducing its accessibility, could account for the low affinity of PBP5fm for beta-lactam. This loop is common to PBPs of low affinity, such as PBP2a from Staphylococcus aureus and PBP3 from Bacillus subtilis. Moreover, the insertion of a serine after residue 466 in the most resistant strains underlines even more the determining role of this loop in the recognition of the substrates.

Research Center/Unit :

CIP - Centre d'Ingénierie des Protéines - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Sauvage, Eric ; Université de Liège - ULiège > Centre d'ingénierie des protéines

Kerff, Frédéric ; Université de Liège - ULiège > Centre d'ingénierie des protéines

Fonze, E.

Herman, Raphaël ; Université de Liège - ULiège > Centre d'ingénierie des protéines

Schoot, B.

Marquette, J. P.

Taburet, Y.

Prevost, D.

Dumas, J.

Stefanic, P.

Coyette, Jacques ; Université de Liège - ULiège > Services généraux (Faculté des sciences) > Relations académiques et scientifiques (Sciences)

Charlier, Paulette ; Université de Liège - ULiège > Département des sciences de la vie > Cristallographie des macromolécules biologiques

Leonard, Gordon

Title :

The 2.4-A crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin.

Journal title :

Cellular and Molecular Life Sciences

Publisher :

Birkhäuser, Basel, Switzerland

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 23 February 2010

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