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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2005-12-2
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pubmed:abstractText |
In a broad genomics analysis to find novel protein targets for antibiotic discovery, MurF was identified as an essential gene product for Streptococcus pneumonia that catalyzes a critical reaction in the biosynthesis of the peptidoglycan in the formation of the cell wall. Lacking close relatives in mammalian biology, MurF presents attractive characteristics as a potential drug target. Initial screening of the Abbott small-molecule compound collection identified several compounds for further validation as pharmaceutical leads. Here we report the integrated efforts of NMR and X-ray crystallography, which reveal the multidomain structure of a MurF-inhibitor complex in a compact conformation that differs dramatically from related structures. The lead molecule is bound in the substrate-binding region and induces domain closure, suggestive of the domain arrangement for the as yet unobserved transition state conformation for MurF enzymes. The results form a basis for directed optimization of the compound lead by structure-based design to explore the suitability of MurF as a pharmaceutical target.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-10089316,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-10356330,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-10395471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-10493791,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-10966819,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-11090285,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-11124264,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-11699883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-12462143,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-12470258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-12492849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-12837790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-1436736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-14684340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-1490109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-15299374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-8634271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-8785318,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16322581-8973200
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0961-8368
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pubmed:author |
pubmed-author:BartleyDiane MDM,
pubmed-author:BeutelBruce ABA,
pubmed-author:EdaljiRohintonR,
pubmed-author:FryElizabeth HEH,
pubmed-author:GuYu GuiYG,
pubmed-author:HajdukPhilip JPJ,
pubmed-author:HarlanJohn EJE,
pubmed-author:HolzmanThomas FTF,
pubmed-author:JakobClarissa GCG,
pubmed-author:LernerClaude GCG,
pubmed-author:LongeneckerKenton LKL,
pubmed-author:SolomonLarry RLR,
pubmed-author:StamperGeoffrey FGF,
pubmed-author:StollVincent SVS,
pubmed-author:WalterKarl AKA
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3039-47
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16322581-Amino Acid Sequence,
pubmed-meshheading:16322581-Binding Sites,
pubmed-meshheading:16322581-Crystallography, X-Ray,
pubmed-meshheading:16322581-Enzyme Inhibitors,
pubmed-meshheading:16322581-Ligands,
pubmed-meshheading:16322581-Models, Molecular,
pubmed-meshheading:16322581-Molecular Sequence Data,
pubmed-meshheading:16322581-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:16322581-Peptide Synthases,
pubmed-meshheading:16322581-Protein Structure, Tertiary,
pubmed-meshheading:16322581-Sequence Alignment,
pubmed-meshheading:16322581-Sequence Homology,
pubmed-meshheading:16322581-Streptococcus pneumoniae,
pubmed-meshheading:16322581-Substrate Specificity
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pubmed:year |
2005
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pubmed:articleTitle |
Structure of MurF from Streptococcus pneumoniae co-crystallized with a small molecule inhibitor exhibits interdomain closure.
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pubmed:affiliation |
Department of Structural Biology, R46Y, Building AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. Kenton.Longenecker@Abbott.com
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pubmed:publicationType |
Journal Article
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