[Mapping of active site of alcohol dehydrogenase with low-molecular ligands].
In search of an active alcohol dehydrogenase inhibitor, the structure of which may serve as the basis for a potential drug design, the active site of alcohol dehydrogenase containing NAD and Zn2+ ions was mapped using the method of molecular mechanics. Molecular docking was performed using a number of ligands containing characteristic functional groups: formate ion, ammonia, ammonium ion, methanol, and methylamine. Sites of preferable binding were revealed for each ligand and arranged in order of decreasing energy of binding to the enzyme. A comparison of the predicted ligand-binding sites and the experimental data on the location of water and inhibitor binding sites in the known structures of corresponding alcohol dehydrogenase complexes indicated a coincidence of the complex formation sites, which confirms the validity of the method and provides the requirements for a highly effective inhibitor (the pharmacophore model).
Kutsenko
A S
AS
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. ku@imb.imb.ac.ru
Kuznetsov
D A
DA
Poroĭkov
V V
VV
Tumanian
V G
VG
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001665:Binding Sites; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular
D004791:Enzyme Inhibitors; D008024:Ligands; D000426:Alcohol Dehydrogenase