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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
2005-6-27
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pubmed:abstractText |
Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not the respective free acids, and to catalyze the hydrolysis of bound fatty acyl-CoAs. The free acid pocket, previously reported in the x-ray structure of HNF-4alpha E-domain, entraps fatty acids but excludes acyl-CoAs. The acyl-CoA and free acid sites are distinctive and noncongruent. Free fatty acid products of HNF-4alpha thioesterase may exchange with free acids entrapped in the fatty acid pocket of HNF-4alpha. Cross-talk between the acyl-CoA and free fatty acid binding sites is abrogated by high affinity, nonhydrolyzable acyl-CoA ligands of HNF-4alpha that inhibit its thioesterase activity. Hence, HNF-4alpha transcriptional activity is controlled by its two interrelated acyl ligands and two binding sites interphased in tandem by the thioesterase activity. The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/4,4-difluoro-4-bora-3a,4a-diaza-s-in...,
http://linkedlifedata.com/resource/pubmed/chemical/Acyl Coenzyme A,
http://linkedlifedata.com/resource/pubmed/chemical/Boron Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thiolester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Triazenes,
http://linkedlifedata.com/resource/pubmed/chemical/triacsin C
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
24451-61
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15870076-Acyl Coenzyme A,
pubmed-meshheading:15870076-Animals,
pubmed-meshheading:15870076-Binding Sites,
pubmed-meshheading:15870076-Boron Compounds,
pubmed-meshheading:15870076-COS Cells,
pubmed-meshheading:15870076-Cell Nucleus,
pubmed-meshheading:15870076-Crystallography, X-Ray,
pubmed-meshheading:15870076-DNA, Complementary,
pubmed-meshheading:15870076-DNA-Binding Proteins,
pubmed-meshheading:15870076-Dose-Response Relationship, Drug,
pubmed-meshheading:15870076-Enzyme Inhibitors,
pubmed-meshheading:15870076-Fatty Acids,
pubmed-meshheading:15870076-Fluorescent Dyes,
pubmed-meshheading:15870076-Hepatocyte Nuclear Factor 4,
pubmed-meshheading:15870076-Kinetics,
pubmed-meshheading:15870076-Ligands,
pubmed-meshheading:15870076-Models, Biological,
pubmed-meshheading:15870076-Phosphoproteins,
pubmed-meshheading:15870076-Plasmids,
pubmed-meshheading:15870076-Protein Binding,
pubmed-meshheading:15870076-Protein Structure, Tertiary,
pubmed-meshheading:15870076-Rats,
pubmed-meshheading:15870076-Recombinant Proteins,
pubmed-meshheading:15870076-Substrate Specificity,
pubmed-meshheading:15870076-Thiolester Hydrolases,
pubmed-meshheading:15870076-Transcription, Genetic,
pubmed-meshheading:15870076-Transcription Factors,
pubmed-meshheading:15870076-Transfection,
pubmed-meshheading:15870076-Triazenes
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pubmed:year |
2005
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pubmed:articleTitle |
Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}.
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pubmed:affiliation |
Department of Human Nutrition and Metabolism, Hebrew University Medical School, Ein-Kerem, P. O. Box 12272, Jerusalem 91120, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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