title: UDP-N-acetylglucosamine enolpyruvyl transferase as a potential target for antibacterial chemotherapy: recent developments.
abstract: The emergence of antibiotic resistance in bacterial pathogens has foxed the health organizations which are actively scrambling for solutions. The available data indicate an increased morbidity in infections often leading to mortality among patients where drug-resistant pathogens have negated the effect of the medicines. In the context of developing "novel bacterial inhibitors" for killing or arresting the growth of drug-resistant pathogens, UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is an enzyme that provides hope for the future. This enzyme catalyzes the first committed step in the biosynthesis of peptidoglycan, an integral and essential component of the bacterial cell wall. MurA enzyme is neither present nor required by mammals and shows poor homology with human proteins. Therefore, it is an ideal target for antibacterial chemotherapy. Till date, 18 structures of MurA (in native and ligand-bound forms) from different bacterial pathogens have been solved. In the last 2 years, eight structures of bacterial MurA have been submitted to the Protein Data Bank and many inhibitors discovered. The present review discusses the structural and functional features of MurA of bacterial pathogens along with the development of MurA-targeted inhibitors.
authors.affiliation: Bioinformatics Centre, Institute of Microbial Technology, Chandigarh 160036, India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Gautam
authors.forename: Praveen
authors.initials: P
authors.lastname: Rishi
authors.forename: Rupinder
authors.initials: R
authors.lastname: Tewari
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; C022566:UDP-N-acetylglucosamine 1-carboxyvinyltransferase