Structural highlights
Function
FABA_PSEAE Necessary for the introduction of cis unsaturation into fatty acids. Catalyzes the dehydration of (3R)-3-hydroxydecanoyl-ACP to E-(2)-decenoyl-ACP and then its isomerization to Z-(3)-decenoyl-ACP. Can catalyze the dehydratase reaction for beta-hydroxyacyl-ACPs with saturated chain lengths up to 16:0, being most active on intermediate chain length (By similarity).
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.
See Also
References
- ↑ Moynie L, Leckie SM, McMahon SA, Duthie FG, Koehnke A, Taylor JW, Alphey MS, Brenk R, Smith AD, Naismith JH. Structural Insights into the Mechanism and Inhibition of the beta-Hydroxydecanoyl-Acyl Carrier Protein Dehydratase from Pseudomonasaeruginosa. J Mol Biol. 2013 Jan 23;425(2):365-77. doi: 10.1016/j.jmb.2012.11.017. Epub 2012 , Nov 19. PMID:23174186 doi:10.1016/j.jmb.2012.11.017