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dc.contributor.authorMoynie, Lucile
dc.contributor.authorLeckie, Stuart M.
dc.contributor.authorMcMahon, Stephen A.
dc.contributor.authorDuthie, Fraser G.
dc.contributor.authorKoehnke, Alessa
dc.contributor.authorTaylor, James W.
dc.contributor.authorAlphey, Magnus S.
dc.contributor.authorBrenk, Ruth
dc.contributor.authorSmith, Andrew D.
dc.contributor.authorNaismith, James H.
dc.identifier.citationMoynie , 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 2013 , ' Structural insights into the mechanism and inhibition of the beta-Hydroxydecanoyl-Acyl carrier protein dehydratase from pseudomonas aeruginosa ' Journal of Molecular Biology , vol. 425 , no. 2 , pp. 365-377 .
dc.identifier.otherPURE: 50488441
dc.identifier.otherPURE UUID: eecc6404-425a-4c7a-9f1b-6873899d78ec
dc.identifier.otherWOS: 000315305700012
dc.identifier.otherScopus: 84872111212
dc.identifier.otherORCID: /0000-0002-2104-7313/work/36567525
dc.description.abstractFatty 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. (C) 2012 Elsevier Ltd. All rights reserved.
dc.relation.ispartofJournal of Molecular Biologyen
dc.rights(c) The authors. This is an open access article, available from http://www.sciencedirect.comen
dc.subjectAntibacterial drug discoveryen
dc.subjectMacromolecular crystallographyen
dc.subjectFatty-acid biosynthesisen
dc.subjectLead discoveryen
dc.subjectCrystal-structure characterizationen
dc.subjectDiffraction dataen
dc.subjectQH301 Biologyen
dc.titleStructural insights into the mechanism and inhibition of the beta-Hydroxydecanoyl-Acyl carrier protein dehydratase from pseudomonas aeruginosaen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.EaSTCHEMen
dc.description.statusPeer revieweden

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