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.
© 2014 International Union of Biochemistry and Molecular Biology.
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