title: Molecular dimensions of the substrate binding site of cytochrome P-448.
abstract: The molecular geometries of specific substrates, inhibitors and inducers of cytochrome P-448 activity were determined using computer-graphic techniques for use in defining the molecular dimensions of the substrate binding site of this enzyme. Specific substrates of cytochrome P-448 are essentially planar molecules characterised by a small depth and a large area/depth ratio. In contrast, compounds that do not serve as substrates of cytochrome P-448 are bulky, non-planar molecules characterised by small area/depth ratios and greater flexibility in molecular conformation. Specific inhibitors of cytochrome P-448 whose effect is mediated through interaction with the haem still meet the dimensional criteria for substrates indicating that they must also interact with the substrate binding-site, which is probably located in proximity to the haem. Inducers of cytochrome P-448 activity exhibit similar molecular geometries to the substrates from which it may be inferred that the cytosolic receptor associated with the induction of cytochrome P-448 activity is structurally related to the active site of the cytochrome.
mesh_terms: D000818:Animals; D001665:Binding Sites; D003201:Computers; D019388:Cytochrome P-450 CYP1A2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003580:Cytochromes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004611:Ellipticines / Q000494:pharmacology; D004790:Enzyme Induction; D006900:Hydroxylation; D008797:Metyrapone / Q000494:pharmacology; D008958:Models, Molecular; D011335:Proadifen / Q000494:pharmacology; D011487:Protein Conformation; D011796:Quinacrine / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D003580:Cytochromes; D004611:Ellipticines; C008009:9-hydroxyellipticine; D011335:Proadifen; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D011796:Quinacrine; D008797:Metyrapone