title: Lipid a biosynthesis of multidrug-resistant pathogens - a novel drug target.
abstract: The rapid increase of human infections by multidrug-resistant (MDR) Gram-negative pathogens poses a serious health threat and demands the identification of new strategies, molecular targets, and agents for the treatment of Gram-negative bacterial infections. The biosynthesis of lipid A, the membrane-anchoring portion of lipopolysaccharide (LPS), is one promising target for novel antibiotic design because lipid A is essential for LPS assembly in most Gram-negative bacteria. The first three enzymes in the biosynthesis of lipid A, UDP-N-acetylglucosamine acyltransferase (LpxA), UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase (LpxC) and UDP- 3-O-(R-3-hydroxyacyl)glucosamine N-acyltransferase (LpxD), have emerged as an attractive Gram-negative antibacterial molecular target. In this article, we review recent advances in the studies on the structures and the structure-based drug designs of the three enzymes.
authors.affiliation: National Leading Research Laboratory, Department of Biological Sciences, Myongji University, 116 Myongjiro, Yongin, Gyeonggido 449-728, Republic of Korea. sangheelee@mju.ac.kr.
authors.forename: Chang-Ro
authors.initials: CR
authors.lastname: Lee
authors.forename: Jung Hun
authors.initials: JH
authors.lastname: Lee
authors.forename: Byeong Chul
authors.initials: BC
authors.lastname: Jeong
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors; D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000472:pathogenicity*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008050:Lipid A / Q000096:biosynthesis*
chemical_list: D004791:Enzyme Inhibitors; D008050:Lipid A; D000217:Acyltransferases; C050304:acyl-(acyl-carrier-protein)-UDP-N-acetylglucosamine acyltransferase; D000581:Amidohydrolases; C097307:UDP-3-O-acyl-N-acetylglucosamine deacetylase