Advanced search
Publication Cover
Expert Opinion on Drug Metabolism & Toxicology Volume 2, 2006 - Issue 4
Submit an article Journal homepage
155
Views
40
CrossRef citations to date
0
Altmetric
Review

Current views on the fundamental mechanisms of cytochrome P450 allosterism

William M Atkins Professor of Medicinal Chemistry, University of Washington, Department of Medicinal Chemistry, Box 357610, Seattle, WA 98195-7610, USA. [email protected]
Pages 573-579 | Published online: 21 Jul 2006

Bibliography

  • TRACY TS, HUTZLER JM, HAININGRL, RETTIE AE, HUMMELMA, DICKMANN LJ: Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: effect on atypical kinetic metabolism profiles. Drug Metab. Dispos. (2002) 30(4):385-390.
  • TRACY TS: Atypical enzyme kinetics: their effect on invitroinvivo pharmacokinetic predictions and drug interactions. Curr. Drug Metab. (2003) 4(5):341-346.
  • ATKINS WM: Non-MichaelisMenten kinetics in cytochrome P450-catalyzed reactions. Ann. Rev. Pharmacol. Toxicol. (2005) 45:291-310.
  • HOUSTON JB, GALETIN A: Modelling atypical CYP3A4 kinetics: principles and pragmatism. Arch. Biochem. Biophys. (2005) 433(2):351-360.
  • TRACY TS, HUMMEL MA: Modeling kinetic data from invitro drug metabolism enzyme experiments. Drug Metab. Rev. (2004) 36(2):231-242.
  • ATKINS WM, WANG RW, LU AY: Allosteric behavior in cytochrome P450-dependent invitro drugdrug interactions: a prospective based on conformational dynamics. Chem. Res. Toxicol. (2001) 14(4):338-347.
  • HLAVICA P, LEWIS DF: Allosteric phenomena in cytochrome P450-catalyzed monooxygenations. Eur. J. Biochem. (2001) 268(18):4817-4832.
  • TANG W, STEARNS RA: Heterotropic cooperativity of cytochrome P450 3A4 and potential drugdrug interactions. Curr. Drug Metab. (2001) 2(2):185-198.
  • EGNELL AC, HOUSTON JB, BOYERCS: Predictive models of CYP3A4 Heteroactivation: invitroinvivo scaling and pharmacophore modeling. J. Pharmacol. Exp. Ther. (2005) 312(3):926-937.
  • TANG W, STEARNS RA, KWEI GY: Interaction of diclofenac and quinidine in monkeys: stimulation of diclofenac metabolism. J. Pharmacol. Exp. Ther. (1999) 291(3):1068-1074.
  • EGNELL AC, HOUSTON B, BOYER S: Invivo CYP3A4 heteroactivation is a possible mechanism for the drug interaction between felbamate and carbamazepine. J. Pharmacol. Exp. Ther. (2003) 305(3):1251-1262.
  • HUTZLER JM, FRYE RF, KORZEKWAKR, BRANCH RA, HUANG SM, TRACY TS: Minimal invivo activation of CYP2C9-mediated flurbiprofen metabolism by dapsone. Eur. J. Pharm. Sci. (2001) 14(1):47-52.
  • GALETIN A, CLARKE SE, HOUSTONJB: Multisite kinetic analysis of interactions between prototypical CYP3A4 subgroup substrates: midazolam, testosterone, and nifedipine. Drug Metab. Dispos. (2003) 31(9):1108-1116.
  • SHOU M: Kinetic analysis for multiple substrate interaction at the active site of cytochrome P450. Methods Enzymol. (2002) 357:261-276.
  • JUSHCHYSHYN MI, HUTZLER JM, SCHRAG ML, WIENKERS LC: Catalytic turnover of pyrene by CYP3A4: evidence that cytochrome b(5) directly induces positive cooperativity. Arch. Biochem. Biophys. (2005) 438:21-28.
  • KUMAR S, DAVYDOV DR, HALPERTJR: Role of cytochrome b(5) in modulating peroxide-supported CYP3A4 activity: evidence for a conformational transition and cytochrome P450 heterogeneity. Drug Metab. Disp. (2005) 33(8):1131-1136.
  • HOSEA NA, MILLER GP, GUENGERICH FP: Elucidation of distinct ligand binding sites for cytochrome P450 3A4. Biochemistry (2000) 39(20):5929-5939.
  • FERNANDO H, HALPERT JR, DAVYDOV DR: Resolution of multiple substrate binding sites in cytochrome P450 3A4: the stoichiometry of the enzymesubstrate complexes probed by FRET and Jobs titration. Biochemistry (2006) 45(13):4199-4209.
  • DAVYDOV DR, BOTCHKAREVA AE, DAVYDOVA NE, HALPERT JR: Resolution of two substrate-binding sites in an engineered cytochrome P450eryF bearing a fluorescent probe. Biophys. J. (2005) 89(1):418-432.
  • LAMPE J, ATKINS WM: Time-resolved fluorescence studies of heterotropic ligand binding to cytochrome P450 3A4 (manuscript in preparation).
  • ISIN EM, GUENGERICH FP: Kinetics and thermodynamics of ligand binding by cytochrome P450 3A4. J. Biol. Chem. (2006) 281(14):9127-9136.
  • KORZEKWA KR, KRISHNAMACHARYN, SHOU M etal.: Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry (1998) 37(12):4137-4147.
  • WILLIAMS PA, COSME J, VINKOVICDM etal.: Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science (2004) 305(5684):683-686.
  • YANO JK, WESTER MR, SCHOCH GA, GRIFFIN KJ, STOUT CD, JOHNSONEF: The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution. J. Biol. Chem. (2004) 279(37):38091-38094.
  • WILLIAMS PA, COSME J, WARD A, ANGOVE HC, MATAK VINKOVIC D, JHOTI H: Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature (2003) 424(6947):464-468.
  • CAMERON MD, WEN B, ALLEN KE etal.: Cooperative binding of midazolam with testosterone and -naphthoflavone within the CYP3A4 active site: a NMR T1 paramagnetic relaxation study. Biochemistry (2005) 44(43):14143-14151.
  • HUMMEL MA, GANNETT PM, AGUILAR JS, TRACY TS: Effector-mediated alteration of substrate orientation in cytochrome P450 2C9. Biochemistry (2004) 43(22):7207-7214.
  • ROBERTS AG, DIAZ MD, LAMPE JN etal.: NMR studies of ligand binding to P450(eryF) provides insight into the mechanism of cooperativity. Biochemistry (2006) 45(6):1673-1684.
  • PEARSON JT, HILL JJ, SWANK J, ISOHERRANEN N, KUNZE KL, ATKINS WM: Surface plasmon resonance analysis of antifungal azoles binding to CYP3A4 with kinetic resolution of multiple binding orientations. Biochemistry (2006) 45(20):6341-6353.
  • ZHAO Y, WHITE MA, MURALIDHARABK, SUN L, HALPERTJR, STOUT CD: Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction. J. Biol. Chem. (2006) 281(9):5973-5981.
  • ROBERTS AG, CAMPBELL AP, ATKINSWM: The thermodynamic landscape of testosterone binding to cytochrome P450 3A4: ligand binding and spin state equilibria. Biochemistry (2005) 44(4):1353-1366.
  • YOON MY, CAMPBELL AP, ATKINSWM: Allosterism in the elementary steps of the cytochrome P450 reaction cycle. Drug Metab. Rev. (2004) 36(2):219-230.
  • DAVYDOV DR, KUMAR S, HALPERTJR: Allosteric mechanisms in P450eryF probed with 1-pyrenebutanol, a novel fluorescent substrate. Biochem. Biophys. Res. Commun. (2002) 294(4):806-812.
  • DAVYDOV DR, HALPERT JR, RENAUD J-P, HUI BON HOA G: Conformational heterogeneity of cytochrome P450 3A4 revealed by high pressure spectroscopy. Biochem. Biophys. Res. Commun. (2003) 312:121-130.
  • KOLEY AP, BUTERS JT, ROBINSONRC, MARKOWITZ A, FRIEDMAN FK: CO binding kinetics of human cytochrome P450 3A4. Specific interaction of substrates with kinetically distinguishable conformers. J. Biol. Chem. (1995) 270(10):5014-5018.
  • KOLEY AP, ROBINSON RC, MARKOWITZ A, FRIEDMAN FK: Drugdrug interactions: effect of quinidine on nifedipine binding to human cytochrome P450 3A4. Biochem. Pharmacol. (1997) 53:455-460.
  • SCOTT EE, WHITE MA, HE YA, JOHNSON EF, STOUT CD, HALPERTJR: Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9-A resolution: insight into the range of P450 conformations and the coordination of redox partner binding. J. Biol. Chem. (2004) 279(26):27294-27301.
  • JOVANOVIC T, MCDERMOTT AE: Observation of ligand binding to cytochrome P450 BM-3 by means of solid-state NMR spectroscopy. J. Am. Chem. Soc. (2005) 127(40):13816-13821.
  • BAAS BJ, DENISOV IG, SLIGAR SG: Homotropic cooperativity of monomeric cytochrome P450 3A4 in a nanoscale native bilayer environment. Arch. Biochem. Biophys. (2004) 430(2):218-228.
  • DAVYDOV DR, FERNANDO H, BAASBJ, SLIGAR SG, HALPERT JR: Kinetics of dithionite-dependent reduction of cytochrome P450 3A4: heterogeneity of the enzyme caused by its oligomerization. Biochemistry (2005) 44(42):13902-13913.
  • DENISOV IG, GRINKOVA YV, LAZARIDES AA, SLIGAR SG: Directed self-assembly of monodisperse phospholipid bilayer nanodiscs with controlled size. J. Am. Chem. Soc. (2004) 126(11):3477-3487.
  • BAYBURT TH, SLIGAR SG: Single-molecule height measurements on microsomal cytochrome P450 in nanometer-scale phospholipid bilayer disks. Proc. Natl. Acad. Sci. USA (2002) 99(10):6725-6730.
  • LOCUSON CW, GANNETT PM, TRACY TS: Heteroactivator effects on the coupling and spin state equilibrium of CYP2C9. Arch. Biochem. Biophys. (2006) 449(1-2):115-129.
  • HUTZLER JM, WIENKERS LC, WAHLSTROM JL, CARLSON TJ, TRACY TS: Activation of cytochrome P450 2C9-mediated metabolism: mechanistic evidence in support of kinetic observations. Arch. Biochem. Biophys. (2003) 410(1):16-24.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.