Chang-Ro Lee, Jung Hun Lee, Byeong Chul Jeong and Sang Hee Lee Pages 6534 - 6550 ( 17 )
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.
Multidrug-resistant pathogens, lipid A biosynthesis, acyltransferase, deacetylase, chemotherapy.
, , , National Leading Research Laboratory, Department of Biological Sciences, Myongji University, 116 Myongjiro, Yongin, Gyeonggido 449-728, Republic of Korea.