title: Catalytic Activities of Tumor-Specific Human Cytochrome P450 CYP2W1 Toward Endogenous Substrates.
abstract: CYP2W1 is a recently discovered human cytochrome P450 enzyme with a distinctive tumor-specific expression pattern. We show here that CYP2W1 exhibits tight binding affinities for retinoids, which have low nanomolar binding constants, and much poorer binding constants in the micromolar range for four other ligands. CYP2W1 converts all-transretinoic acid (atRA) to 4-hydroxyatRA and all-transretinol to 4-OH all-transretinol, and it also oxidizes retinal. The enzyme much less efficiently oxidizes 17β-estradiol to 2-hydroxy-(17β)-estradiol and farnesol to a monohydroxylated product; arachidonic acid is, at best, a negligible substrate. These findings indicate that CYP2W1 probably plays an important role in localized retinoid metabolism that may be intimately linked to its involvement in tumor development.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.).
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.).
authors.forename: Debin
authors.initials: D
authors.lastname: Wan
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.).
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.).
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.) Ortiz@cgl.ucsf.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Ortiz de Montellano
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D002384:Catalysis; D000072467:Cytochrome P450 Family 2 / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D012176:Retinoids / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
chemical_list: D008024:Ligands; D012176:Retinoids; D016718:Arachidonic Acid; D004958:Estradiol; D014212:Tretinoin; C509336:CYP2W1 protein, human; D000072467:Cytochrome P450 Family 2