title: Mechanism based representation of the active site of 5 alpha-reductase (5AR).
abstract: In the present study, we have attempted to determine a detailed representation of the 5 alpha-Reductase (5AR) active site involving the elucidation of the transition state for the steroid delta 4 reduction reaction (the 'NADPH-substrate' complex), onto which steroidal and non-steroidal inhibitors were superimposed. We conclude that: (i) there is a requirement for groups to mimic the steroid substrate A-ring; (ii) the area about C(3), C(4), C(5) and C(6) of T appears to be sterically hindered, and; (iii) the area of the active site about the C(17) of the steroid substrate does not possess hydrogen bonding groups and is not restricted.
authors.affiliation: School of Applied Chemistry, Kingston University, Kingston upon Thames, Surrey, UK. CH_S534@KINGSTON.AC.UK
authors.forename: S
authors.initials: S
authors.lastname: Ahmed
authors.forename: S
authors.initials: S
authors.lastname: Denison
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D018120:Finasteride / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D008956:Models, Chemical; D008958:Models, Molecular; D009249:NADP / Q000378:metabolism; D011278:Pregnanes / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000378:metabolism
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D004791:Enzyme Inhibitors; D011278:Pregnanes; D013196:Dihydrotestosterone; D013739:Testosterone; D009249:NADP; D018120:Finasteride; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; C037399:4-methyl-4-aza-3-oxopregnane-20-carboxylate; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C084634:turosteride