4b0i

Publication Abstract from PubMed

Fatty acid biosynthesis is an essential component of metabolism in both eukaryotes and prokaryotes. The fatty acid biosynthetic pathway of Gram-negative bacteria is an established therapeutic target. Two homologous enzymes FabA and FabZ catalyze a key step in fatty acid biosynthesis; both dehydrate hydroxyacyl fatty acids that are coupled via a phosphopantetheine to an acyl carrier protein (ACP). The resulting trans-2-enoyl-ACP is further polymerized in a processive manner. FabA, however, carries out a second reaction involving isomerization of trans-2-enoyl fatty acid to cis-3-enoyl fatty acid. We have solved the structure of Pseudomonas aeruginosa FabA with a substrate allowing detailed molecular insight into the interactions of the active site. This has allowed a detailed examination of the factors governing the second catalytic step. We have also determined the structure of FabA in complex with small molecules (so-called fragments). These small molecules occupy distinct regions of the active site and form the basis for a rational inhibitor design program.

Structural Insights into the Mechanism and Inhibition of the beta-Hydroxydecanoyl-Acyl Carrier Protein Dehydratase from Pseudomonasaeruginosa.,Moynie L, Leckie SM, McMahon SA, Duthie FG, Koehnke A, Taylor JW, Alphey MS, Brenk R, Smith AD, Naismith JH J Mol Biol. 2013 Jan 23;425(2):365-77. doi: 10.1016/j.jmb.2012.11.017. Epub 2012 , Nov 19. PMID:23174186^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.