Abstract
Docking experiments using a number of published crystal structures of HMG-CoA reductase with the potent hypocholesterolemic agent alpha-asarone are described. The results indicate that alpha-asarone binds in the enzyme's active site. The methoxy groups play a key role in the binding and probably also in its biological activity, as shown by extensive SAR studies reported for analogues of alpha-asarone. The docking results will be valuable for the structure-based design of novel hypolipidemic agents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allylbenzene Derivatives
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Anisoles / chemistry*
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Binding Sites
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Catalytic Domain
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Computer Simulation*
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Humans
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Hydrophobic and Hydrophilic Interactions
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Hydroxymethylglutaryl CoA Reductases / chemistry*
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry*
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Models, Molecular
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Protein Binding
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Structure-Activity Relationship
Substances
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Allylbenzene Derivatives
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Anisoles
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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asarone
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Hydroxymethylglutaryl CoA Reductases