Affiliation:
1. 1Fakulteta za farmacijo, Univerza v Ljubljani, Aškerčeva 7, SI-1000 Ljubljana, Slovenia
2. 2Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR 8619 CNRS, Université Paris-Sud, F-91405 Orsay, France
Abstract
AbstractThe synthesis of the peptide stem of bacterial peptidoglycan involves four enzymes, the Mur ligases (MurC, D, E and F). Among them, MurD is responsible for the ATP-dependent addition of d-glutamic acid to UDP-MurNAc-l-Ala, a reaction which involves acyl-phosphate and tetrahedral intermediates. Like most enzymes of peptidoglycan biosynthesis, MurD constitutes an attractive target for the design and synthesis of new antibacterial agents. Escherichia coli MurD has been the first Mur ligase for which the tridimensional (3D) structure was solved. Thereafter, several co-crystal structures with different ligands or inhibitors were released. In the present review, we will deal with work performed on substrate specificity, reaction mechanism and 3D structure of E. coli MurD. Then, a part of the review will be devoted to recent work on MurD orthologs from species other than E. coli and to cellular organization of Mur ligases and in vivo regulation of the MurD activity. Finally, we will review the different classes of MurD inhibitors that have been designed and assayed to date with the hope of obtaining new antibacterial compounds.
Subject
Cellular and Molecular Neuroscience,General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference196 articles.
1. The lecture discovery of antibacterial drugs in the st century;Chopra,2012
2. de structure architecture;Vollmer;FEMS Microbiol Rev,2008
3. Characterization of a eukaryotic type serine / threonine protein kinase and protein phosphatase ofStreptococcus pneumoniaeand identification of kinase substrates;Nováková;FEBS J,2005
4. van de de Identification of FtsW as a transporter of lipid - linked cell wall precursors across the membrane;Mohammadi;EMBO J,2011
5. Contribution of the Pmrapromoter to expression of genes in theEscherichia coli mracluster of cell envelope biosynthesis and cell division genes;Mengin;J Bacteriol,1998
Cited by
30 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献