Cytochrome P450 substrate specificities, substrate structural templates and enzyme active site geometries.
The structural characteristics of human cytochrome P450 substrates are outlined in the light of extensive studies on P450 substrate specificity. Templates of superimposed substrates for individual P450 isozymes are shown to fit the corresponding enzyme active sites, where contacts with specific amino acid residues appear to be involved in the interaction with each structural template. Procedures leading to the evaluation of likely P450 specificity, binding affinity and rate of metabolism are described in the context of key examples in which molecular modelling appears to rationalize experimentally observed findings.
Lewis
D F
DF
School of Biological Sciences, University of Surrey, Guildford, UK.
Dickins
M
M
Eddershaw
P J
PJ
Tarbit
M H
MH
Goldfarb
P S
PS
D000818:Animals; D001665:Binding Sites; D019388:Cytochrome P-450 CYP1A2 / Q000737:chemistry / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000737:chemistry / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011817:Rabbits; D051381:Rats; D013379:Substrate Specificity
D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6