Source:http://linkedlifedata.com/resource/pubmed/id/11792710
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
2002-4-8
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pubmed:abstractText |
The human malaria parasite Plasmodium falciparum synthesizes fatty acids using a type II pathway that is absent in humans. The final step in fatty acid elongation is catalyzed by enoyl acyl carrier protein reductase, a validated antimicrobial drug target. Here, we report the cloning and expression of the P. falciparum enoyl acyl carrier protein reductase gene, which encodes a 50-kDa protein (PfENR) predicted to target to the unique parasite apicoplast. Purified PfENR was crystallized, and its structure resolved as a binary complex with NADH, a ternary complex with triclosan and NAD(+), and as ternary complexes bound to the triclosan analogs 1 and 2 with NADH. Novel structural features were identified in the PfENR binding loop region that most closely resembled bacterial homologs; elsewhere the protein was similar to ENR from the plant Brassica napus (root mean square for Calphas, 0.30 A). Triclosan and its analogs 1 and 2 killed multidrug-resistant strains of intra-erythrocytic P. falciparum parasites at sub to low micromolar concentrations in vitro. These data define the structural basis of triclosan binding to PfENR and will facilitate structure-based optimization of PfENR inhibitors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Infective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Enoyl-(Acyl-Carrier-Protein)...,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Triclosan
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13106-14
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11792710-Amino Acid Sequence,
pubmed-meshheading:11792710-Animals,
pubmed-meshheading:11792710-Anti-Infective Agents,
pubmed-meshheading:11792710-Base Sequence,
pubmed-meshheading:11792710-Cloning, Molecular,
pubmed-meshheading:11792710-DNA Primers,
pubmed-meshheading:11792710-Enoyl-(Acyl-Carrier-Protein) Reductase (NADH),
pubmed-meshheading:11792710-Models, Molecular,
pubmed-meshheading:11792710-Molecular Sequence Data,
pubmed-meshheading:11792710-Oxidoreductases,
pubmed-meshheading:11792710-Plasmodium falciparum,
pubmed-meshheading:11792710-Protein Structure, Tertiary,
pubmed-meshheading:11792710-Sequence Homology, Amino Acid,
pubmed-meshheading:11792710-Substrate Specificity,
pubmed-meshheading:11792710-Triclosan
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pubmed:year |
2002
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pubmed:articleTitle |
Structural elucidation of the specificity of the antibacterial agent triclosan for malarial enoyl acyl carrier protein reductase.
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pubmed:affiliation |
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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