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The crystal structure of the penicillin-binding protein 2x from Streptococcus pneumoniae and its acyl-enzyme form: implication in drug resistance.

Gordon E, Mouz N, Duée E, Dideberg O
J Mol Biol 299 477-85 (2000)
Related entries: 1pmd, 1qme

Cited: 122 times
EuropePMC logo PMID: 10860753

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.

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Related citations provided by authors (2)

  1. X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme.. Pares S, Mouz N, Pétillot Y, Hakenbeck R, Dideberg O Nat Struct Biol 3 284-9 (1996)
  2. Crystallization of a genetically engineered water-soluble primary penicillin target enzyme. The high molecular mass PBP2x of Streptococcus pneumoniae.. Charlier P, Buisson G, Dideberg O, Wierenga J, Keck W, Laible G, Hakenbeck R J Mol Biol 232 1007-9 (1993)

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