Computational site-directed mutagenesis studies of the role of the hydrophobic triad on substrate binding in cholesterol oxidase
|dc.identifier.citation||Harb, L. and Arooj, M. and Vrielink, A. and Mancera, R. 2017. Computational site-directed mutagenesis studies of the role of the hydrophobic triad on substrate binding in cholesterol oxidase. Proteins: Function, Structure, and Bioinformatics. 85 (9): pp. 1645-1655.|
Â© 2017 Wiley Periodicals, Inc. Cholesterol oxidase (ChOx) is a flavoenzyme that oxidizes and isomerizes cholesterol (CHL) to form cholest-4-en-3-one. Molecular docking and molecular dynamics simulations were conducted to predict the binding interactions of CHL in the active site. Several key interactions (E361-CHL, N485-FAD, and H447-CHL) were identified and which are likely to determine the correct positioning of CHL relative to flavin-adenine dinucleotide (FAD). Binding of CHL also induced changes in key residues of the active site leading to the closure of the oxygen channel. A group of residues, Y107, F444, and Y446, known as the hydrophobic triad, are believed to affect the binding of CHL in the active site. Computational site-directed mutagenesis of these residues revealed that their mutation affects the conformations of key residues in the active site, leading to non-optimal binding of CHL and to changes in the structure of the oxygen channel, all of which are likely to reduce the catalytic efficiency of ChOx. Proteins 2017; 85:1645â€“1655. Â© 2017 Wiley Periodicals, Inc.
|dc.publisher||John Wiley & Sons, Inc.|
|dc.title||Computational site-directed mutagenesis studies of the role of the hydrophobic triad on substrate binding in cholesterol oxidase|
|dcterms.source.title||Proteins: Function, Structure, and Bioinformatics|
|curtin.department||School of Biomedical Sciences|
|curtin.accessStatus||Fulltext not available|
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