title: MurD enzymes: some recent developments.
abstract: The 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.
authors.forename: Roman
authors.initials: R
authors.lastname: Šink
authors.forename: Hélène
authors.initials: H
authors.lastname: Barreteau
authors.forename: Delphine
authors.initials: D
authors.lastname: Patin
authors.forename: Dominique
authors.initials: D
authors.lastname: Mengin-Lecreulx
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D010453:Peptide Synthases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010453:Peptide Synthases; C053379:UDP-N-acetylmuramoylalanine-D-glutamate ligase