title: Penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fishovitz
authors.forename: Juan A
authors.initials: JA
authors.lastname: Hermoso
authors.forename: Mayland
authors.initials: M
authors.lastname: Chang
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D015780:Carbapenems / Q000737:chemistry; D002473:Cell Wall / Q000378:metabolism*; D002511:Cephalosporins / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D046915:Penicillin-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010406:Penicillins / Q000737:chemistry; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism
chemical_list: D015780:Carbapenems; D002511:Cephalosporins; D003432:Cross-Linking Reagents; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D047090:beta-Lactams; C478699:penicillin-binding protein 2a, Streptococcus; D010453:Peptide Synthases
keywords: allosteric regulation; conformational change; methicillin-resistant Staphylococcus aureus; resistance mechanism; β-lactam antibiotics