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Review

Allosteric P450 mechanisms: multiple binding sites, multiple conformers or both?

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Pages 1523-1535 | Published online: 28 Nov 2008

Bibliography

  • Ingelman-Sundberg M, Johansson I, Hansson A. Catalytic properties of the liver microsomal hydroxylase system in reconstituted phospholipid vesicles. Acta Biol Med Ger 1979;38:379-88
  • Brueggemeier RW. Kinetics of rat liver microsomal estrogen 2-hydroxylase. Evidence for sex differences at initial velocity conditions. J Biol Chem 1981;256:10239-42
  • Johnson EF, Schwab GE, Dieter HH. Allosteric regulation of the 16α-hydroxylation of progesterone as catalyzed by rabbit microsomal cytochrome P-450 3b. J Biol Chem 1983;258:2785-8
  • Johnson EF, Schwab GE. Constitutive forms of rabbit-liver microsomal cytochrome P-450: enzymatic diversity, polymorphism and allosteric regulation. Xenobiotica 1984;14:3-18
  • Schwab GE, Raucy JL, Johnson EF. Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by α-naphthoflavone. Mol Pharmacol 1988;33:493-9
  • Johnson EF, Schwab GE, Vickery LE. Positive effectors of the binding of an active site-directed amino steroid to rabbit cytochrome P-450 3c. J Biol Chem 1988;263:17672-7
  • Raney KD, Shimada T, Kim DH, et al. Oxidation of aflatoxins and sterigmatocystin by human liver microsomes: significance of aflatoxin Q1 as a detoxication product of aflatoxin B1. Chem Res Toxicol 1992;5:202-10
  • Ueng YF, Shimada T, Yamazaki H, Guengerich FP. Oxidation of aflatoxin B1 by bacterial recombinant human cytochrome P450 enzymes. Chem Res Toxicol 1995;8:218-25
  • Wang RW, Newton DJ, Liu N, et al. Human cytochrome P-450 3A4: In vitro. drug-drug interaction patterns are substrate-dependent. Drug Metab Disp 2000;28:360-6
  • Shou M, Dai R, Cui D, et al. A kinetic model for the metabolic interaction of two substrates at the active site of cytochrome P450 3A4. J Biol Chem 2001;276:2256-62
  • Guengerich FP. Cytochrome P450 and chemical toxicology. Chem Res Toxicol 2008;21:70-83
  • Lasker JM, Huang MT, Conney AH. In vivo activation of zoxazolamine metabolism by flavone. Science 1982;216:1419-21
  • Lasker JM, Huang MT, Conney AH. In vitro and in vivo activation of oxidative drug-metabolism by flavonoids. J Pharmacol Exp Ther 1984;229:162-70
  • Maenpaa J, Hall SD, Ring BJ, et al. Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism: the effect of assay conditions and regioselective stimulation by alpha-naphthoflavone, terfenadine and testosterone. Pharmacogenet 1998;8:137-55
  • Witherow LE, Houston JB. Sigmoidal kinetics of CYP3A substrates: An approach for scaling dextromethorphan metabolism in hepatic microsomes and isolated hepatocytes to predict in vivo clearance in rat. J Pharmacol Exp Ther 1999;290:58-65
  • Tang W, Stearns RA, Bandiera SM, et al. Studies on cytochrome P-450-mediated bioactivation of diclofenac in rats and. Drug Metab Disp 1999;27:365-72
  • Hutzler JM, Hauer MJ, Tracy TS. Dapsone activation of CYP2C9-mediated metabolism: Evidence for activation of multiple substrates and a two-site model. Drug Metab Disp 2001;29:1029-34
  • Tang W, Stearns RA. Heterotropic cooperativity of cytochrome P450 3A4 and potential drug-drug interactions. Curr Drug Metab 2001;2:185-98
  • Henshall J, Galetin A, Harrison A, et al. Comparative analysis of CYP3A heteroactivation by steroid hormones and flavonoids in different in vitro systems and potential in vivo implications. Drug Metab Disp 2008;36:1332-40
  • Kiselev PA, Garda G, Finch SA, et al. Regulation of the catalytic activity of the monooxygenase enzyme system depending of the substrate structure and phospholipid composition of the model membrane. Biochemistry (Moscow) 1990;55:1535-44
  • Ekins S, Stresser DM, Williams JA. In vitro and pharmacophore insights into CYP3A enzymes. Trends Pharm Sci 2003;24:161-6
  • Lampe JN, Fernandez C, Nath A, et al. Nile red is a fluorescent allosteric substrate of cytochrome P450 3A4. Biochem47:509-16
  • Lin Y, Lu P, Tang C, et al. Substrate inhibition kinetics for cytochrome P450-catalyzed reactions. Drug Metab Disp 2001;29:368-74
  • Sohl CD, Isin EM, Eoff RL, et al. Cooperativity in oxidation reactions catalyzed by cytochrome P450 1A2 - Highly cooperative pyrene hydroxylation and multiphasic kinetics of ligand binding. J Biol Chem 2008;283:7293-308
  • Harrelson JP, Atkins WM, Nelson SD. Multiple-ligand binding in CYP2A6: Probing mechanisms of cytochrome P450 cooperativity by assessing substrate dynarnics. Biochem 2008;47:2978-88
  • Shou M, Grogan J, Mancewicz JA, et al. Activation of CYP3A4 - evidence for the simultaneous binding of 2 substrates. Biochem 1994;33:6450-5
  • Korzekwa KR, Krishnamachary N, Shou M, et al. Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochem 1998;37:4137-47
  • Ueng YF, Kuwabara T, Chun YJ, et al. Cooperativity in oxidations catalyzed by cytochrome P450 3A4. Biochem 1997;36:370-81
  • Domanski TL, He YA, Khan KK, et al. Phenylalanine and tryptophan scanning mutagenesis of CYP3A4 substrate recognition site residues and effect on substrate oxidation and cooperativity. Biochem 2001;40:10150-60
  • Yoon MY, Campbell AP, Atkins WM. “Allosterism” in the elementary steps of the cytochrome P450 reaction cycle. Drug Metab Rev 2004;36:219-30
  • He YA, Roussel F, Halpert JR. Analysis of homotropic and heterotropic cooperativity of diazepam oxidation. Arch Biochem Biophys 2003;409:92-101
  • Hosea NA, Miller GP, Guengerich FP. Elucidation of distinct ligand binding sites for cytochrome P450 3A4. Biochem 2000;39:5929-39
  • Ngui JS, Chen Q, Shou MG, et al. In vitro stimulation of warfarin metabolism by quinidine: Increases in the formation of 4 ‘ - and 10-hydroxywarfarin. Drug Metab Disp 2001;29:877-86
  • Harlow GR, Halpert JR. Analysis of human cytochrome P450 3A4 cooperativity: construction and characterization of a site-directed mutant that displays hyperbolic steroid hydroxylation kinetics. Proc Natl Acad Sci USA 1998;95:6636-41
  • Cupp-Vickery J, Anderson R, Hatziris Z. Crystal structures of ligand complexes of P450eryF showing homotropic cooperativity. Proc Natl Acad Sci USA 2000;97:3050-5
  • Fernando H, Halpert JR, Davydov DR. Resolution of multiple substrate binding sites in cytochrome P450 3A4: the stoichiometry of the enzyme–substrate complexes probed by FRET and Job's titration. Biochem 2006;45:4199-209
  • Dabrowski MJ, Schrag ML, Wienkers L, et al. Pyrene-pyrene complexes at the active site of cytochrome P450 3A4: evidence for a multiple substrate binding site. J Am Chem Soc 2002;124:11866-7
  • Cameron MD, Wen B, Roberts AG, et al. Cooperative binding of acetaminophen and caffeine within the P450 3A4 active site. Chem Res Toxicol 2007;20:1434-41
  • Roberts AG, Campbell AP, Atkins WM. The thermodynamic landscape of testosterone binding to cytochrome P450 3A4: ligand binding and spin state equilibria. Biochem 2005;44:1353-66
  • Baas BJ, Denisov IG, Sligar SG. Homotropic cooperativity of monomeric cytochrome P450 3A4 in a nanoscale native bilayer environment. Arch Biochem Biophys 2004;430:218-28
  • Denisov IG, Baas BJ, Grinkova YV, et al. Cooperativity in cytochrome P450 3A4 - Linkages in substrate binding, spin state, uncoupling, and product formation. J Biol Chem 2007;282:7066-76
  • Ekroos M, Sjogren T. Structural basis for ligand promiscuity in cytochrome P450 3A4. Proc Natl Acad Sci USA 2006;103:13682-7
  • Galetin A, Clarke SE, Houston JB. Quinidine and haloperidol as modifiers of CYP3A4 activity: Multisite kinetic model approach. Drug Metab Disp 2002;30:1512-22
  • Galetin A, Clarke SE, Houston JB. Multisite kinetic analysis of interactions between prototypical CYP3A4 subgroup substrates: Midazolam, testosterone, and nifedipine. Drug Metab Disp 2003;31:1108-16
  • Funahashi T, Tanaka Y, Yamaori S, et al. Stimulatory Effects of Testosterone and Progesterone on the NADH- and NADPH-dependent Oxidation of 7delta-Hydroxy-beta8-tetrahydrocannabinol to 7-Oxo-beta8-tetrahydrocannabinol in Monkey Liver Microsomes. Drug Metab Pharmacokinetics 2005;20:358-67
  • Lu P, Lin Y, Rodrigues AD, et al. Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin bind to different domains within the active site of cytochrome P450 3A4. Drug Metab Disp 2001;29:1473-9
  • Ngui JS, Tang W, Stearns RA, et al. Cytochrome P450 3A4-mediated interaction of diclofenac and quinidine. Drug Metab Disp 2000;28:1043-50
  • Houston B, Galetin A. Progress Towards Prediction of Human Pharmacokinetic Parameters from In Vitro Technologies. Drug Metab Rev 2003;35:393-415
  • Houston JB, Galetin A. Modelling atypical CYP3A4 kinetics: principles and pragmatism. Arch Biochem Biophys 2005;433:351-60
  • Schrag ML, Wienkers LC. Covalent alteration of the CYP3A4 active site: Evidence for multiple substrate binding domains. Arch Biochem Biophys 2001;391:49-55
  • Egnell AC, Houston JB, Boyer CS. Predictive models of CYP3A4 heteroactivation: in vitro-in vivo scaling and pharmacophore modelling. J Pharmacol Exp Ther 2005;312:926-37
  • Kenworthy KE, Clarke SE, Andrews J, et al. Multisite kinetic models for CYP3A4: simultaneous activation and inhibition of diazepam and testosterone metabolism. Drug Metab Disp 2001;29:1644-51
  • Kenworthy KE, Bloomer JC, Clarke SE, et al. CYP3A4 drug interactions: correlation of 10 in vitro probe substrates. Brit J Clin Pharmacol 1999;48:716-27
  • He YA, Gajiwala KS, Wu M, et al. The crystal structure of human CYP3A4 in complex with testosterone. In Abstracts, 16th International Symposium on Microsomes and Drug Oxidations (MDO 2006), August 10-14 2006, Budapest, Hungary;2006:114
  • Tsalkova TN, Davydova NY, Halpert JR, et al. Mechanism of interactions of alpha-naphthoflavone with cytochrome P450 3A4 explored with an engineered enzyme bearing a fluorescent probe. Biochem 2007;46:106-19
  • Isin EM, Guengerich FP. Kinetics and thermodynamics of ligand binding by cytochrome P450 3A4. J Biol Chem 2006;281:9127-36
  • Nath A, Fernandez C, Lampe JN, et al. Spectral resolution of a second binding site for Nile Red on cytochrome P4503A4. Arch Biochem Biophys 2008;474:198-204
  • Atkins WM, Wang RW, Lu AYH. Allosteric behavior in cytochrome P450-dependent in vitro drug-drug interactions: A prospective based on conformational dynamics. Chem Res Toxicol 2001;14:338-47
  • Atkins WM. Implications of the allosteric kinetics of cytochrome P450s. Drug Discovery Today 2004;9:478-84
  • Davydov DR, Botchkareva AE, Davydova NY, et al. Resolution of two substrate-binding sites in an engineered cytochrome P450eryF bearing a fluorescent probe. Biophys J 2005;89:418-32
  • Atkins WM. Current views on the fundamental mechanisms of cytochrome P450 allosterism. Expert Opinion Drug Metab Toxicol 2006;2:573-9
  • Lampe JN, Atkins WM. Time-resolved fluorescence studies of heterotropic ligand binding to cytochrome P450 3A4. Biochem 2006;45:12204-15
  • Davydov DR, Botchkareva AE, Kumar S, et al. An electrostatically driven conformational transition is involved in the mechanisms of substrate binding and cooperativity in cytochrome P450eryF. Biochem 2004;43:6475-85
  • Davydov DR, Fernando H, Baas BJ, et al. Kinetics of dithionite-dependent reduction of cytochrome P450 3A4: heterogeneity of the enzyme caused by its oligomerization. Biochem 2005;44:13902-13
  • Fernando H, Halpert JR, Davydov DR. Kinetics of electron transfer in the complex of cytochrome P450 3A4 with the flavin domain of cytochrome P450BM-3 as evidence of functional heterogeneity of the heme protein. Arch Biochem Biophys 2008;471:20-31
  • Zhao YH, Halpert JR. Structure-function analysis of cytochrornes P4502B. Biochim Biophys Acta 2007;1770:402-412
  • Williams PA, Cosme J, Ward A, et al. Crystal structure of human cytochrome P4502C9 with bound warfarin. Nature 2003;424:464-8
  • Wester MR, Yano JK, Schoch GA, et al. The structure of human cytochrome P4502C9 complexed with flurbiprofen at 2.0-angstrom resolution. J Biol Chem 2004;279:35630-37
  • Schrag ML, Wienkers LC. Topological alteration of the CYP3A4 active site by the divalent cation Mg2+. Drug Metab Disp 2000;28:1198-201
  • Davydov DR, Baas BJ, Sligar SG, et al. Allosteric mechanisms in cytochrome P450 3A4 studied by high-pressure spectroscopy: pivotal role of substrate-induced changes in the accessibility and degree of hydration of the heme pocket. Biochem 2007;46:7852-64
  • Davydov DR, Davydova NY, Halpert JR. Allosteric transitions in cytochrome P450eryF explored with pressure-perturbation spectroscopy, lifetime FRET, and a novel fluorescent substrate, Fluorol-7GA. Biochem 2008;47:11348-59
  • Denisov IG, Grinkova YV, Baas BJ, et al. The ferrous-dioxygen intermediate in human cytochrome P450 3A4. Substrate dependence of formation and decay kinetics. J Biol Chem 2006;281:23313-8
  • Davydov DR, Halpert JR. Cytochrome P450eryF as an allosteric enzyme: substrate-induced transitions revealed by time-resolved FRET and pressure perturbation studies with Fluorol-7GA, a novel fluorescent substrate. In: 9th International Symposium on Cytochrome P450 Biodiversity and Biotechnology. June 8-12, 2008, Nice, France. Program and Abstracts, P-05
  • Davydov DR, Fernando H, Halpert JR. Alteration of cooperativity in cytochrome P450 3A4 mutants F213W, L211F/D214E and F304W studied with a novel fluorescent allosteric ligand, Fluorol-7GA. Manuscript in preparation
  • Koley AP, Buters JTM, Robinson RC, et al. Cytochrome P450 conformation and substrate interactions as probed by CO binding kinetics. Biochimie 1996;78:706-13
  • Koley AP, Buters JTM, Robinson RC, et al. Differential mechanisms of cytochrome P450 inhibition and activation by α-naphthoflavone: J Biol Chem 1997;272:3149-52
  • Koley AP, Robinson RC, Markowitz A, et al. Drug-drug interactions: effect of quinidine on nifedipine binding to human cytochrome P450 3A4. Biochem Pharm 1997;53:455-60
  • Davydov DR, Karyakin AV, Binas B, et al. Kinetic studies on reduction of cytochromes P-450 and b5 by dithionite. Eur J Biochem 1985;150:155-9
  • Ledenev AN, Tverdokhlebov EN, Davydov RM. Reduction of Ferricytochrome P-450 with Eosin Photoradical. Biofizika 1984;29:730-732
  • Davydov RM, Khanina OY, Iagofarov S, et al. Effect of lipids and substrates on the kinetics of interactions of ferrocytochrome P-450 with CO. Biokhimiia 1986;51:125-9
  • Koley AP, Buters JT, Robinson RC, et al. CO binding kinetics of human cytochrome P450 3A4. Specific interaction of substrates with kinetically distinguishable conformers. J Biol Chem 1995;270:5014-8
  • Tsong TY, Yang CS. Rapid conformational changes of cytochrome P-450: effect of dimyristoyl lecithin. Proc Nat Acad Sci USA 1978;75:5955-9
  • Fisher MT, Sligar SG. Temperature jump relaxation kinetics of the P-450cam spin equilibrium. Biochem 1987;26:4797-803
  • Brenner S, Hay S, Girvan HM, et al. Conformational dynamics of the cytochrome P450BM3/N-palmitoylglycine complex: The proposed “proximal-distal” transition probed by temperature-jump spectroscopy. J Phys Chem B 2007;111:7879-86
  • Backes WL, Tamburini PP, Jansson I, et al. Kinetics of cytochrome P-450 reduction: evidence for faster reduction of the high-spin ferric state. Biochem 1985;24:5130-6
  • Hildebrandt P, Heibel G, Anzenbacher P, et al. Conformational analysis of mitochondrial and microsomal cytochrome P-450 by resonance Raman spectroscopy. Biochem 1994;33:12920-9
  • Davydov DR, Knyushko TV, Hui Bon Hoa G. High pressure induced inactivation of ferrous cytochrome P-450 LM2 (2B4) CO complex: evidence for the presence of two conformers in the oligomer. Biochem Biophys Res Commun 1992;188:216-21
  • Davydov DR, Deprez E, Hui Bon Hoa G, et al. High-pressure-induced transitions in microsomal cytochrome P450 2B4 in solution - evidence for conformational inhomogeneity in the oligomers. Arch Biochem Biophys 1995;320:330-44
  • Davydov DR, Halpert JR, Renaud JP, et al. Conformational heterogeneity of cytochrome P450 3A4 revealed by high pressure spectroscopy. Biochem Biophys Res Commun 2003;312:121-30
  • Bancel F, Bec N, Ebel C, Lange R. A central role for water in the control of the spin state of cytochrome P-450(scc). Eur J Biochem 1997;250:276-85
  • Anzenbacherova E, Hudecek J, Murgida D, et al. Active sites of two orthologous cytochromes P450 2E1: Differences revealed by spectroscopic methods. Biochem Biophys Res Commun 2005;338:477-82
  • Kumar S, Davydov DR, Halpert JR. Role of cytochrome b5 in modulating peroxide-supported CYP3A4 activity: Evidence for a conformational transition and cytochrome P450 heterogeneity. Drug Metab Disp 2005;33:1131-6
  • Hui Bon Hoa G, Davydov DR, Ponomarev GV. Application of high pressure fluorescence spectroscopy to study protein-protein interactions of cytochrome P450. In: Proceedings of the XXXII EHPRG meeting; Leuven, Belgium: Catholic University of Leuven 1997:107-10
  • Richter C, Winterhalter KH, Cherry RJ. Rotational diffusion of cytochrome P-450 in rat liver microsomes. FEBS Lett 1979;102:151-4
  • Mcintosh PR, Kawato S, Freedman RB, et al. Evidence from cross-linking and rotational diffusion studies that cytochrome P450 can from molecular aggregates in rabbit-liver microsomal membranes. FEBS Lett 1980;122:54-8
  • Gut J, Richter C, Cherry RJ, et al. Rotation of cytochrome P-450. Complex formation of cytochrome P-450 with NADPH-cytochrome P-450 reductase in liposomes demonstrated by combining protein rotation with antibody-induced cross-linking. J Biol Chem 1983;258:8588-94
  • Gut J, Kawato S, Cherry RJ, et al. Lipid peroxidation decreases the rotational mobility of cytochrome P-450 in rat liver microsomes. Biochim Biophys Acta 1985;817:217-28
  • Hildebrandt P, Garda H, Stier A, et al. Protein-protein interactions in microsomal cytochrome P-450 isozyme LM2 and their effect on substrate binding. Eur J Biochem 1989;186:383-8
  • Kawato S, Ashikawa I, Iwase T, et al. Drug-induction decreases the mobility of cytochrome P-450 in rat liver microsomes: protein rotation study. J Biochem 1991;109:587-93
  • Schwarz D, Pirrwitz J, Ruckpaul K. Rotational diffusion of cytochrome P-450 in the microsomal membrane-evidence for a clusterlike organization from saturation transfer electron paramagnetic resonance spectroscopy. Arch Biochem Biophys 1982;216:322-8
  • Schwarz D, Pirrwitz J, Meyer HW, et al. Membrane topology of microsomal cytochrome P-450: Saturation transfer EPR and freeze-fracture electron microscopy studies. Biochem Biophys Res Commun 1990;171:175-81
  • Greinert R, Finch SA, Stier A. Cytochrome P-450 rotamers control mixed-function oxygenation in reconstituted membranes. Rotational diffusion studied by delayed fluorescence depolarization. Xenobiotica 1982;12:717-26
  • Szczesna-Skorupa E, Mallah B, Kemper B. Fluorescence resonance energy transfer analysis of cytochromes P450 2C2 and 2E1 molecular interactions in living cells. J Biol Chem 2003;278:31269-76
  • Alston K, Robinson RC, Park SS, et al. Interactions among cytochromes P-450 in the endoplasmic reticulum. Detection of chemically cross-linked complexes with monoclonal antibodies. J Biol Chem 1991;266:735-9
  • Davydov DR, Petushkova NA, Bobrovnikova EV, et al. Association of cytochromes P450 1A2 and 2B4: Are the interactions between different P450 species involved in the control of the monooxygenase activity and coupling? Adv Exp Med Biol 2001;500:335-8
  • Schwarz D, Chernogolov L, Kisselev P. Complex formation in vesicle-reconstituted mitochondrial cytochrome P450 systems (CYP11A1 and CYP11B1) as evidenced by rotational diffusion experiments using EPR and ST-EPR. Biochem 1999;38:9456-64
  • Iwase T, Sakaki T, Yabusaki Y et al. Rotation and interactions of genetically expressed cytochrome P-450IA1 and NADPH-cytochrome P-450 reductase in yeast microsomes. Biochem 1991;30:8347-51
  • Yamada M, Ohta Y, Bachmanova GI, et al. Dynamic interactions of rabbit liver cytochromes P450IA2 and P450IIB4 with cytochrome b5 and NADPH-cytochrome P450 reductase in proteoliposomes. Biochem 1995;34:10113-9
  • Greinert R, Finch SA, Stier A. Conformation and rotational diffusion of cytochrome P-450 changed by substrate binding. Biosci Reports 1982;2:991-4
  • Richter C. Biophysical consequences of lipid peroxidation in membranes. Chem Phys Lipids 1987;44:175-89
  • Jansson I, Curti M, Epstein PM, et al. Relationship between phosphorylation and cytochrome P450 destruction. Arch Biochem Biophys 1990;283:285-92
  • Davydov DR, Halpert JR. Allosteric mechanisms in cytochrome P450: conformational transition in CYP3A4 caused by the binding of alpha-naphthoflavone. FASEB J 2004;18:C178
  • Fernando H, Davydov DR, Chin CC, Halpert JR. Role of subunit interactions in P450 oligomers in the loss of homotropic cooperativity in the cytochrome P450 3A4 mutant L211F/D214E/F304W. Arch Biochem Biophys 2007;460:129-40
  • Reed JR, Hollenberg PF. Comparison of substrate metabolism by cytochromes P4502B1, 2B4, and 2B6: relationship of heme spin state, catalysis, and the effects of cytochrome b5. J Inorg Biochem 2003;93:152-60
  • Hlavica P, Lewis DFV. Allosteric phenomena in cytochrome P450-catalyzed monooxygenations. Eur J Biochem 2001;268:4817-32
  • Jansson I, Schenkman JB. Substrate influence on interaction between cytochrome P450 and cytochrome b5. Arch Biochem Biophys 1996;325:265-9
  • Backes WL, Eyer CS. Cytochrome P-450 LM2 reduction. Substrate effects on the rate of reductase-LM2 association. J Biol Chem 1989;264:6252-9
  • Tamburini PP, Gibson GG. Thermodynamic studies of the protein-protein interactions between cytochrome P-450 and cytochrome b5. Evidence for a central role of the cytochrome P-450 spin state in the coupling of substrate and cytochrome b5 binding to the terminal hemoprotein. J Biol Chem 1983;258:13444-52
  • Schlichting I, Berendzen J, Chu K, et al. The catalytic pathway of cytochrome P450cam at atomic resolution. Science 2000;287:1615-22
  • Loida PJ, Sligar SG. Molecular recognition in cytochrome P-450: mechanism for the control of uncoupling reactions. Biochem 1993;32:11530-8
  • Wade RC, Gabdoulline RR, Ludemann SK, et al. Electrostatic Steering and Ionic Tethering in Enzyme-Ligand Binding-Insights from Simulations. Proc Natl Acad Sci USA 1998;95:5942-9
  • Lounnas V, Ludemann SK, Wade RC. Towards molecular dynamics simulation of large proteins with a hydration shell at constant pressure. Biophys Chem 1999;78:157-82
  • Davydov DR, Kumar S, Halpert JR. Allosteric mechanisms in P450eryF probed with 1-pyrenebutanol, a novel fluorescent substrate. Biochem Biophys Res Commun 2002;294:806-12
  • Williams PA, Cosme J, Vinkovic DM, et al. Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science 2004;305:683-6
  • Schoch GA, Yano JK, Wester MR, et al. Structure of human microsomal cytochrome P4502C8 - Evidence for a peripheral fatty acid binding site. J Biol Chem 2004;279:9497-503
  • Davydov DR, Davydova NY, Tsalkova TN, et al. Effect of glutathione on homo- and heterotropic cooperativity in cytochrome P450 3A4. Arch Biochem Biophys 2008;471:134-45
  • Backes WL, Kelley RW. Organization of multiple cytochrome P450s with NADPH-cytochrome P450 reductase in membranes. Pharm Ther 2003;98:221-33
  • Kaminsky LS, Guengerich FP. Cytochrome P-450 isozyme/isozyme functional interactions and NADPH-cytochrome P-450 reductase concentrations as factors in microsomal metabolism of warfarin. Eur J Biochem 1985;149:479-89
  • Yamazaki H, Gillam EM, Dong MS, et al. Reconstitution of recombinant cytochrome P450 2C10(2C9) and comparison with cytochrome P450 3A4 and other forms: effects of cytochrome P450- P450 and cytochrome P450-b5 interactions. Arch Biochem Biophys 1997;342:329-37
  • Backes WL, Batie CJ, Cawley GF. Interactions among P450 Enzymes When Combined in Reconstituted Systems: formation of a 2B4-1A2 Complex with a High Affinity for NADPH- Cytochrome P450 Reductase. Biochem 1998;37:12852-9
  • Cawley GF, Zhang SX, Kelley RW, et al. Evidence supporting the interaction of CYP2B4 and CYP1A2 in microsomal preparations. Drug Metab Disp 2001;29:1529-34
  • Davydov DR, Petushkova NA, Archakov AI, et al. Stabilization of P450 2B4 by its association with P450 1A2 revealed by high-pressure spectroscopy. Biochem Biophys Res Commun 2000;276:1005-12
  • Kelley WK, Reed JR, Backes WL. Effect of ionic strength on the functional interactions between CYP2B4 and CYP1A2. Biochem 2005;44:2632-41

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