4FQ9

Crystal Structure of 3-hydroxydecanoyl-Acyl Carrier Protein Dehydratase (FabA) from Pseudomonas aeruginosa

Summary for 4FQ9

• Entry DOI: 10.2210/pdb4fq9/pdb
• Descriptor: 3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase, PHOSPHATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: lyase, hot dog fold, fatty acid biosynthesis, bacterial virulence
• Biological source: Pseudomonas aeruginosa
• Cellular location: Cytoplasm (By similarity): O33877
• Total number of polymer chains: 10
• Total formula weight: 190310.70

Authors

Moynie, L.,Mcmahon, S.A.,Duthie, F.G.,Naismith, J.H. (deposition date: 2012-06-25, release date: 2013-03-27, Last modification date: 2024-02-28)

Primary citation

Moynie, L.,Leckie, S.M.,McMahon, S.A.,Duthie, F.G.,Koehnke, A.,Taylor, J.W.,Alphey, M.S.,Brenk, R.,Smith, A.D.,Naismith, J.H.
Structural insights into the mechanism and inhibition of the beta-hydroxydecanoyl-acyl carrier protein dehydratase from Pseudomonas aeruginosa
J.Mol.Biol., 425:365-377, 2013

PubMed Abstract: 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.

PubMed: 23174186
DOI: 10.1016/j.jmb.2012.11.017

Experimental method

X-RAY DIFFRACTION (2.02 Å)