4B0J

Crystal Structure of 3-hydroxydecanoyl-Acyl Carrier Protein Dehydratase (FabA) from Pseudomonas aeruginosa in complex with 5-(2- thienyl)-3-isoxazolyl methanol

Summary for 4B0J

• Entry DOI: 10.2210/pdb4b0j/pdb
• Related: 4B0B 4B0C 4B0I
• Descriptor: 3-HYDROXYDECANOYL-[ACYL-CARRIER-PROTEIN] DEHYDRATASE, (5-thiophen-2-ylisoxazol-3-yl)methanol (3 entities in total)
• Functional Keywords: lyase, fatty acid biosynthesis, bacterial virulence, drug discovery
• Biological source: PSEUDOMONAS AERUGINOSA
• Total number of polymer chains: 20
• Total formula weight: 378994.90

Authors

Moynie, L.,McMahon, S.A.,Duthie, F.G.,Naismith, J.H. (deposition date: 2012-07-02, release date: 2012-11-28, Last modification date: 2023-12-20)

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 (2.5 Å)