Penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus

IUBMB Life. 2014 Aug;66(8):572-7. doi: 10.1002/iub.1289. Epub 2014 Jul 14.

Abstract

High-level resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) is due to expression of penicillin-binding protein 2a (PBP2a), a transpeptidase that catalyzes cell-wall crosslinking in the face of the challenge by β-lactam antibiotics. The activity of this protein is regulated by allostery at a site 60 Å distant from the active site, where crosslinking of cell wall takes place. This review discusses the state of knowledge on this important enzyme of cell-wall biosynthesis in MRSA.

Keywords: allosteric regulation; conformational change; methicillin-resistant Staphylococcus aureus; resistance mechanism; β-lactam antibiotics.

Publication types

  • Review

MeSH terms

  • Allosteric Regulation / physiology
  • Carbapenems / chemistry
  • Cell Wall / metabolism*
  • Cephalosporins / chemistry
  • Cross-Linking Reagents / metabolism*
  • Drug Resistance, Bacterial / genetics*
  • Methicillin-Resistant Staphylococcus aureus / genetics*
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Models, Molecular*
  • Molecular Structure
  • Penicillin-Binding Proteins / chemistry
  • Penicillin-Binding Proteins / genetics*
  • Penicillin-Binding Proteins / metabolism
  • Penicillins / chemistry
  • Peptide Synthases / chemistry
  • Peptide Synthases / genetics*
  • Peptide Synthases / metabolism
  • beta-Lactams / metabolism

Substances

  • Carbapenems
  • Cephalosporins
  • Cross-Linking Reagents
  • Penicillin-Binding Proteins
  • Penicillins
  • beta-Lactams
  • penicillin-binding protein 2a, Streptococcus
  • Peptide Synthases