Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 299 (2), 477-85

The Crystal Structure of the Penicillin-Binding Protein 2x From Streptococcus Pneumoniae and Its Acyl-Enzyme Form: Implication in Drug Resistance

Affiliations

The Crystal Structure of the Penicillin-Binding Protein 2x From Streptococcus Pneumoniae and Its Acyl-Enzyme Form: Implication in Drug Resistance

E Gordon et al. J Mol Biol.

Abstract

Penicillin-binding proteins (PBPs), the primary targets for beta-lactam antibiotics, are periplasmic membrane-attached proteins responsible for the construction and maintenance of the bacterial cell wall. Bacteria have developed several mechanisms of resistance, one of which is the mutation of the target enzymes to reduce their affinity for beta-lactam antibiotics. Here, we describe the structure of PBP2x from Streptococcus pneumoniae determined to 2.4 A. In addition, we also describe the PBP2x structure in complex with cefuroxime, a therapeutically relevant antibiotic, at 2.8 A. Surprisingly, two antibiotic molecules are observed: one as a covalent complex with the active-site serine residue, and a second one between the C-terminal and the transpeptidase domains. The structure of PBP2x reveals an active site similar to those of the class A beta-lactamases, albeit with an absence of unambiguous deacylation machinery. The structure highlights a few amino acid residues, namely Thr338, Thr550 and Gln552, which are directly related to the resistance phenomenon.

Similar articles

See all similar articles

Cited by 64 PubMed Central articles

See all "Cited by" articles

MeSH terms

LinkOut - more resources

Feedback