title: The derivation of a potential transition state for the reduction reaction catalysed by 17beta-hydroxysteroid dehydrogenase--an approximate representation of its active site for use in drug design and discovery.
abstract: In an effort to aid the drug discovery process, the approximate representation of the active site of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) has been derived from the consideration of the proposed mechanism for the reduction reaction. Using the transition-state (TS), the mode of action of a number of inhibitors has been rationalised. The results of the study suggest that the area of the active site corresponding to the C(17) area of the steroidal backbone is relatively constrained, as such, groups which possess large groups that are flexible in nature may possess a decreased inhibitory activity. The model is therefore a good start point for the development of novel inhibitors of 17beta-HSD and is a rapid technique for drug design and development.
authors.affiliation: Department of Pharmacy, School of Chemical and Pharmaceutical Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK.
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Owen
authors.forename: Sabbir
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D013256:Steroids; D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase