Source:http://linkedlifedata.com/resource/pubmed/id/18061544
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2007-12-17
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| pubmed:abstractText |
Medium-chain acyl-CoA dehydrogenase (MCAD) and acyl-CoA oxidase (ACO) are key enzymes catalyzing the rate-determining step for the beta-oxidation of fatty acids. Tyr375 of MCAD is conserved in all acyl-CoA dehydrogenases and is an important residue for substrate binding. Four Tyr375 variant enzymes of rat liver MCAD were obtained through site-directed mutagenesis. Y375K was found to have intrinsic acyl-CoA oxidase activity, which was confirmed using HPLC analysis, while the wild-type and other Tyr375 variant enzymes did not show detectable oxidase activity. The kinetic parameters for the oxidase activity of Y375K variant enzyme were determined to be k(cat) of 320+/-80 h(-1) and K(M) of 30+/-15 microM using hexanoyl-CoA as the substrate. The oxidase activity of Y375K increased more than 200 times compared with that reported for the MCAD wild-type enzyme from mammalian sources. Molecular modeling study shows that the solvent accessible area for Y375K variant enzyme is wider than that of the wild-type enzyme, which indicates that Tyr375 may function as a switch against solvent accession. The mutation of this residue to Lys375 allows molecular oxygen to enter into the catalytic site serving as the electron acceptor for the reduced FAD cofactor.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acyl-CoA Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Acyl-CoA Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Coenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Flavin-Adenine Dinucleotide,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0006-3002
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
1774
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1628-34
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| pubmed:meshHeading |
pubmed-meshheading:18061544-Acyl-CoA Dehydrogenase,
pubmed-meshheading:18061544-Acyl-CoA Oxidase,
pubmed-meshheading:18061544-Amino Acid Substitution,
pubmed-meshheading:18061544-Animals,
pubmed-meshheading:18061544-Base Sequence,
pubmed-meshheading:18061544-Catalytic Domain,
pubmed-meshheading:18061544-Coenzymes,
pubmed-meshheading:18061544-Flavin-Adenine Dinucleotide,
pubmed-meshheading:18061544-Liver,
pubmed-meshheading:18061544-Lysine,
pubmed-meshheading:18061544-Models, Biological,
pubmed-meshheading:18061544-Models, Molecular,
pubmed-meshheading:18061544-Mutagenesis, Site-Directed,
pubmed-meshheading:18061544-Mutant Proteins,
pubmed-meshheading:18061544-Mutation,
pubmed-meshheading:18061544-Rats,
pubmed-meshheading:18061544-Substrate Specificity,
pubmed-meshheading:18061544-Tyrosine
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| pubmed:year |
2007
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| pubmed:articleTitle |
Mutation of Tyr375 to Lys375 allows medium-chain acyl-CoA dehydrogenase to acquire acyl-CoA oxidase activity.
|
| pubmed:affiliation |
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, PR China; Department of Bioengineering, School of Resources Processing and Bioengineering, Central South University, Changsha 410083, PR China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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