Modelling Human Cytochrome P450-Substrate Interactions
The cytochromes P450 (CYP) are extremely important and ubiquitous enzymes, being present in virtually all species studied to date and across the five biological kingdoms where they are associated with the phase I oxidative metabolism of a large number of structurally diverse chemicals, both exogenous and endogenous (Ortiz de Montellano 1995; Ioannides 1996; Lewis 1996, 2001; Rendic and DiCarlo 1997). Of the 1,200 or more P450s sequenced thus far, it has been established that a relatively small number (~10) of the human hepatic enzymes metabolize over 90% of the known drugs in current clinical use, with the CYP2C, CYP2D and CYP3A subfamilies constituting the major catalysts of drug metabolism in man (Rendic and DiCarlo 1997).
KeywordsLauric Acid Haem Iron Putative Active Site Active Site Amino Acid Residue Nicotinamide Adenine Dinu
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- loannides C (1996) Cytochromes P450: Metabolic and Toxicological Aspects, CRC Press, Boca Raton, FloridaGoogle Scholar
- Lewis DFV (1996) Cytochromes P450: Structure, function and mechanism. Taylor and Francis, LondonGoogle Scholar
- Lewis DFV, Lake BG, Dickins M, Eddershaw PJ, Tarbit MH, Goldfarb PS (1999c) Molecular modelling of CYP2B6, the human CYP2B isoform, by homology with the substrate-bound CYP102 crystal structure: evaluation of CYP2B6 substrate characteristics, the cytochrome b5 binding site and comparisons with CYP2B 1 and CYP2B4. Xenobiotica 29: 361–393PubMedCrossRefGoogle Scholar
- Lewis DFV, Bird MG, Dickins M, Lake BG, Eddershaw PJ, Tarbit MH, Goldfarb PS (2000) Molecular modelling of human CYP2E1 by homology with the CYP102 haemoprotein domain: investigation of the interactions of substrates and inhibitors within the putative active site of the human CYP2E1 isoform. Xenobiotica 30: 1–25PubMedCrossRefGoogle Scholar