Source:http://linkedlifedata.com/resource/pubmed/id/11027148
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
41
|
| pubmed:dateCreated |
2000-11-7
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| pubmed:abstractText |
The substitution of the C=O by the C=S group in 2-azaoctanoyl-CoA increases the volume of the ligand by 11 A(3), and the excision of a methylene group from Glu-376, via Glu-376 --> Asp (E376D) mutation in medium chain acyl-CoA dehydrogenase (MCAD), creates a complementary cavity of 18 A(3) dimension, just opposite to the ligand's carbonyl group. We investigated whether the newly created cavity would facilitate accommodation of the bulkier (C=O --> C=S substituted) ligand within the active site of the enzyme. To ascertain this, we determined the binding affinity and kinetics of association and dissociation of 2-azaoctanoyl-CoA and the C=O --> C=S substituted ligand, 2-azadithiooctanoyl-CoA, involving the wild-type and Glu-376 --> Asp mutant enzymes. The experimental data revealed that the binding of 2-azadithiooctanoyl-CoA to the wild-type enzyme was energetically unfavorable as compared to 2-azaoctanoyl-CoA. However, such an energetic constraint was alleviated for the binding of the former ligand to the E376D mutant enzyme site. A detailed account of the free energy and enthalpic profiles for the binding of 2-azaoctanoyl-CoA and 2-azadithiooctanoyl-CoA to the wild-type and Glu-376 --> Asp mutant enzymes throws light on the flexibility of the enzyme site cavity in stabilizing the ground and transition states of the enzyme-ligand complexes.
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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 Coenzyme A,
http://linkedlifedata.com/resource/pubmed/chemical/Acyl-CoA Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Acyl-CoA Dehydrogenases,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/octanoyl-coenzyme A
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
17
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| pubmed:volume |
39
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
12678-87
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11027148-Acyl Coenzyme A,
pubmed-meshheading:11027148-Acyl-CoA Dehydrogenase,
pubmed-meshheading:11027148-Acyl-CoA Dehydrogenases,
pubmed-meshheading:11027148-Amino Acid Substitution,
pubmed-meshheading:11027148-Animals,
pubmed-meshheading:11027148-Aspartic Acid,
pubmed-meshheading:11027148-Binding Sites,
pubmed-meshheading:11027148-Catalysis,
pubmed-meshheading:11027148-Glutamic Acid,
pubmed-meshheading:11027148-Humans,
pubmed-meshheading:11027148-Kidney,
pubmed-meshheading:11027148-Kinetics,
pubmed-meshheading:11027148-Ligands,
pubmed-meshheading:11027148-Liver,
pubmed-meshheading:11027148-Models, Molecular,
pubmed-meshheading:11027148-Mutagenesis, Site-Directed,
pubmed-meshheading:11027148-Oxidation-Reduction,
pubmed-meshheading:11027148-Spectrophotometry,
pubmed-meshheading:11027148-Swine,
pubmed-meshheading:11027148-Temperature,
pubmed-meshheading:11027148-Thermodynamics,
pubmed-meshheading:11027148-Titrimetry
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| pubmed:year |
2000
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| pubmed:articleTitle |
Energetic consequences of accommodating a bulkier ligand at the active site of medium chain acyl-CoA dehydrogenase by creating a complementary enzyme site cavity.
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| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, North Dakota State University, Fargo, North Dakota 58105, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, Non-P.H.S.
|