@article{Nasser2004Therm-8321,
  year={2004},
  title={Thermal unfolding of medium-chain acyl-CoA dehydrogenase and iso(3)valeryl-CoA dehydrogenase : study of the effect of genetic defects on enzyme stability},
  number={1},
  volume={1690},
  issn={0925-4439},
  journal={Biochimica et Biophysica Acta},
  pages={22--32},
  author={Nasser, Ibrahim and Mohsen, Al-Walid and Jelesarov, Ilian and Vockley, Jerry and Macheroux, Peter and Ghisla, Sandro}
}

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    <dc:creator>Vockley, Jerry</dc:creator>
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    <dc:creator>Jelesarov, Ilian</dc:creator>
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    <dc:contributor>Macheroux, Peter</dc:contributor>
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    <dc:creator>Mohsen, Al-Walid</dc:creator>
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    <dc:creator>Macheroux, Peter</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:42:39Z</dc:date>
    <dc:contributor>Mohsen, Al-Walid</dc:contributor>
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    <dcterms:title>Thermal unfolding of medium-chain acyl-CoA dehydrogenase and iso(3)valeryl-CoA dehydrogenase : study of the effect of genetic defects on enzyme stability</dcterms:title>
    <dc:contributor>Jelesarov, Ilian</dc:contributor>
    <dc:contributor>Nasser, Ibrahim</dc:contributor>
    <dcterms:abstract xml:lang="eng">Genetic defects affecting acyl-CoA dehydrogenases (ACAD) key enzymes in the degradation of fatty acids and branched chain amino acids are increasingly recognized as being more widespread than originally thought. For the medium-chain acyl-CoA dehydrogenase (MCAD), the K304E mutation is the most common genetic defect among Caucasian populations. The effect of substrate or substrate analog binding on the stability of wild-type MCAD and isovaleryl-CoA dehydrogenase (i3VD) and their genetic mutants (K304E- and T168A-MCAD and A282V-i3VD) is examined. Binding to the mutant ACADs is generally ≈10-fold weaker compared to wild-type proteins. Thermal stability of wt-MCAD (melting point ≈53.6 °C) is significantly higher compared to wt-i3VD (≈49.3 °C). With the exception of the A282V-i3VD mutant, a high degree of stabilization (5 11 °C) is induced by conversion into the reduced enzyme form complexed with product. The results are discussed based on the 3D-structures of the enzymes, and it is concluded that in the case of K304E-MCAD thermal stability as such is not a major contribution to the clinical phenotype. With the T168A-MCAD and A282V-i3VD mutants, however, the diminished thermal stability and minor stabilization by ligands must be regarded as an important factor contributing to the manifestation of the disease.</dcterms:abstract>
    <dcterms:bibliographicCitation>First publ. in: Biochimica et Biophysica Acta / Molecular basis of disease, 1690 (2004), 1, pp. 22-32</dcterms:bibliographicCitation>
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