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Mechanisms of electron transfer from cytochrome P450 reductase to cytochrome P450 3A4

By Yassar Farooq

Abstract

The study demonstrates that CPR and P450 3A4 can be prepared to highly pure state by the use of detergent CHAPS. Optimisation of published methods led to pure flavoprotein, ~90% full-length with a small amount of truncated CPR. The reconstitution of CPR and P450 3A4 into liposomes using CHAPS and Superose 6 column purification has achieved a homogenous highly functional proteoliposomes with good catalytic activity and almost completely reducible P450 3A4 in a simple controllable system. The spectroscopic data has shown that reduction of P450 3A4 in proteoliposomes was at least 10 fold higher than in the simple reconstituted system suggesting that isolation of proteoliposomes from unbound protein aggregates had marked effect on the catalytic activity of P450. Negative staining electron microscopy has revealed proteoliposomes of having mean diameter of 200 ±15 nm in size; the lipid:protein ratio indicated that they incorporated 350 proteins per liposome. Type 1 difference spectral changes were observed upon binding of testosterone and erythromycin. Measurements of the first electron transfer have shown that the reduction of P450 3A4 is highly dependent on the presence of substrate. P450 3A4 reduction in proteoliposomes in the presence of testosterone was rapid and biphasic, with 90% of the P450 reduced in the fast phase, whereas reduction in the presence of erythromycin was monophasic, but substantially slower. Changes in the CPR:P450 molar ratio did not alter the rate of reduction and thus the data strongly indicates that first electron transfer occurs through preformed CPR:P450 complexes in the proteoliposomes that have a lifetime of about order of hundreds of milliseconds. The origin of the slow phase of reduction of P450 is not conclusive from our experiments, but it may be due to P450 heterogeneity. NADPH oxidation and 6β-hydroxytestosterone formation results have revealed that P450 3A4 is highly uncoupled enzyme with rates limited by CPR to P450 3A4 ratio. Hyperbolic plots of rates of NADPH consumption and 6β hydroxytestosterone formation vs CPR concentration indicate apparent Ks of 0.4 μM. This suggests that CPR:P450 complex can dissociate and reform between first and second electron transfer, which in turn indicates that second electron transfer occurs by diffusion mechanism

Publisher: University of Leicester
Year: 2010
OAI identifier: oai:lra.le.ac.uk:2381/8597

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  1. (1997). 1H, 15N and 13C NMR resonance assignment, secondary structure and global fold of the FMN-binding domain of human cytochrome P450 reductase.
  2. (1997). A general strategy for the expression of recombinant human cytochrome P450s in Escherichia coli using bacterial signal peptides: expression of CYP3A4, CYP2A6, and CYP2E1.
  3. (1976). A thermodynamic model of regulation: modulation of redox equilibria in camphor monoxygenase.
  4. (1994). Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site.
  5. (1990). Activation of mitomycin C by NADPH:cytochrome P-450 reductase.
  6. (2005). Activation of molecular oxygen by cytochrome P450.
  7. (2001). Activities and kinetic mechanisms of native and soluble NADPH-cytochrome P450 reductase.
  8. (1997). Alanine-scanning mutagenesis of a putative substrate recognition site in human cytochrome P450 3A4. Role of residues 210 and 211 in flavonoid activation and substrate specificity.
  9. (2006). An evaluation of methods for the reconstitution of cytochromes P450 and NADPH P450 reductase into lipid vesicles.
  10. (2003). Analysis of homotropic and heterotropic cooperativity of diazepam oxidation by CYP3A4 using site-directed mutagenesis and kinetic modeling.
  11. (1998). Analysis of human cytochrome P450 3A4 cooperativity: construction and characterization of a site-directed mutant that displays hyperbolic steroid hydroxylation kinetics.
  12. (2000). Association of cytochromes P450 with their reductases: opposite sign of the electrostatic interactions in P450BM-3 as compared with the microsomal 2B4 system.
  13. (2002). Association of multiple developmental defects and embryonic lethality with loss of microsomal NADPHcytochrome P450 oxidoreductase.
  14. (1991). Atomic structure of ferredoxinNADP+ reductase: prototype for a structurally novel flavoenzyme family.
  15. (1971). Biochemical and genetic factors influencing drug metabolism. Influence of hepatic microsomal mixed function oxidation reactions on cellular metabolic control.
  16. (2005). Biodiversity of cytochrome P450 redox systems.
  17. (1972). Carbon monoxide binding by Pseudomonas putida cytochrome P-450.
  18. (1980). Catalytic properties of purified forms of rabbit liver microsomal cytochrome P-450 in reconstituted phospholipid vesicles.
  19. (1986). Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium.
  20. (1986). Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism.
  21. (2000). Cloning and characterization of a novel human dual flavin reductase.
  22. (1998). Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria.
  23. (1995). CO binding kinetics of human cytochrome P450 3A4. Specific interaction of substrates with kinetically distinguishable conformers.
  24. (1980). Colorimetric determination of phospholipids with ammonium ferrothiocyanate.
  25. (2005). Comparative analysis of amino acid distributions in integral membrane proteins from 107 genomes.
  26. (1995). Comparative analysis of cytochrome P4503A induction in primary cultures of rat, rabbit, and human hepatocytes.
  27. (2004). Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants.
  28. (2007). Conformational dynamics and the energetics of protein--ligand interactions: role of interdomain loop in human cytochrome P450 reductase.
  29. (2003). Conformational heterogeneity of cytochrome P450 3A4 revealed by high pressure spectroscopy.
  30. (2007). Cooperativity in cytochrome P450 3A4 - Linkages in substrate binding, spin state, uncoupling, and product formation.
  31. (1997). Cooperativity in oxidations catalyzed by cytochrome P450 3A4.
  32. (2007). Cooperativity in P450 CYP3A4: Linkages in substrate binding, spin state, uncoupling and product formation.
  33. (1993). Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's.
  34. (2004). Crystal structure of putidaredoxin reductase from Pseudomonas putida, the final structural component of the cytochrome P450cam monooxygenase.
  35. (2003). Crystal structure of putidaredoxin, the [2Fe-2S] component of the P450cam monooxygenase system from Pseudomonas putida.
  36. (2004). Crystal structure of the cytochrome p450cam mutant that exhibits the same spectral perturbations induced by putidaredoxin binding.
  37. (1999). Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution.
  38. (2004). Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone.
  39. (1996). Crystallization and preliminary X-ray diffraction studies of human cytochrome P450 reductase.
  40. (1981). Cytochrome b5 as electron donor for oxy-cytochrome P-450.
  41. (1979). Cytochrome b5 reduction by NADPHcytochrome P-450 reductase.
  42. (2007). Cytochrome b5 stimulates the rate of product formation by cytochrome P450 2B4 and competes with cytochrome P450 reductase for a binding site on cytochrome P450 2B4.
  43. (1995). Cytochrome b5, its functions, structure and membrane topology.
  44. (1999). Cytochrome P-450 3A4: regulation and role in drug metabolism.
  45. (1989). Cytochrome P-450 LM2 reduction. Substrate effects on the rate of reductase-LM2 association.
  46. (1989). Cytochrome P-450: cytochrome P450 reductase interactions.
  47. (2000). Cytochrome P450 3A4-mediated interaction of diclofenac and quinidine.
  48. (1996). Cytochrome P450 conformation and substrate interactions as probed by CO binding kinetics.
  49. (2007). Cytochrome P450--redox partner fusion enzymes.
  50. (2004). Cytochrome P450s in Plant, In:.
  51. (2001). Cytochromes P450 and metabolism of xenobiotics.
  52. (2006). Cytochromes P450 as versatile biocatalysts.
  53. (1995). Cytochromes P450 expression systems.
  54. (1996). Cytochromes P450: Structure, Function
  55. (1997). Detection of free radicals produced from the reaction of cytochrome P-450 with linoleic acid hydroperoxide.
  56. (1994). Determination of membrane-bound fragments of cytochrome P-450 2B4.
  57. (2001). Determination of the redox properties of human NADPH-cytochrome P450 reductase.
  58. (1994). Dissection of NADPH-cytochrome P450 oxidoreductase into distinct functional domains.
  59. (2009). Domain motion in cytochrome P450 reductase: conformational equilibria revealed by NMR and small-angle X-ray scattering.
  60. (1984). Effect of a zwitterionic detergent on the state of aggregation and catalytic activity of cytochrome P-450LM2 and NADPHcytochrome P-450 reductase.
  61. (1982). Effect of spin state on reduction of cytochrome P-450 (P-450C21) from bovine adrenocortical microsomes.
  62. (1998). Electron shuttle between membrane-bound cytochrome P450 3A4 and b5 rules uncoupling mechanisms.
  63. (2004). Electron transfer by diflavin reductases.
  64. (2005). Electron Transfer Partners of Cytochrome P450.
  65. (1988). Electrostatic interactions between cytochrome P-450 LM2 and NADPH-cytochrome P-450 reductase.
  66. (2000). Elucidation of distinct ligand binding sites for cytochrome P450 3A4.
  67. (2007). Energetics of heterotropic cooperativity between alpha-naphthoflavone and testosterone binding to CYP3A4.
  68. (1999). Enhancement of cytochrome P-450 3A4 catalytic activities by cytochrome b(5) in bacterial membranes.
  69. (1992). Enhancement of doxorubicin toxicity following activation by NADPH cytochrome P450 reductase.
  70. (2003). Examining the mechanism of stimulation of cytochrome P450 by cytochrome b5: the effect of cytochrome b5 on the interaction between cytochrome P450 2B4 and P450 reductase.
  71. (1993). Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme.
  72. (1998). Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms.
  73. (2006). Global effects of the energetics of coenzyme binding: NADPH controls the protein interaction properties of human cytochrome P450 reductase.
  74. (1996). Heme-Containing Oxygenases.
  75. (1996). High rates of substrate hydroxylation by human cytochrome P450 3A4 in reconstituted membranous vesicles: influence of membrane charge.
  76. (2004). Homotropic cooperativity of monomeric cytochrome P450 3A4 in a nanoscale native bilayer environment.
  77. (2004). Human cytochrome P450 enzymes. In:.
  78. (2004). Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms.
  79. (2010). Hydrocarbon hydroxylation by cytochrome P450 enzymes.
  80. (1982). Hydrodynamic properties of monomeric cytochromes P-450LM2 and P-450LM4 in n-octylglucoside solution.
  81. (1991). Identification and characterization of an NADPH-cytochrome P450 reductase derived peptide involved in binding to cytochrome P450.
  82. (1998). Identification of the binding site on cytochrome P450 2B4 for cytochrome b5 and cytochrome P450 reductase.
  83. (1990). Immobilized cytochrome P-450LM2. Dissociation and reassociation of oligomers.
  84. (1972). Immunochemical evidence for an association of heme oxygenase with the microsomal electron transport system.
  85. (1982). Immunochemical evidence for induction of a common form of hepatic cytochrome P-450 in rats treated with pregnenolone-16 alpha-carbonitrile or other steroidal or non-steroidal agents.
  86. (1998). In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol,
  87. (2001). In vitro stimulation of warfarin metabolism by quinidine: increases in the formation of 4'- and 10-hydroxywarfarin. Drug Metab Dispos,
  88. (2003). Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase.
  89. (2001). Induction of cytochromes P450.
  90. (1987). Influence of cytochrome b5 on the stoichiometry of the different oxidative reactions catalyzed by liver microsomal cytochrome P-450. Drug Metab Dispos,
  91. (2003). Infrared spectroscopic and mutational studies on putidaredoxin-induced conformational changes in ferrous CO-P450cam.
  92. (2004). Inhibition of cytochrome P450 enzymes.
  93. (2000). Inhibitory effect of natural furanocoumarins on human microsomal cytochrome P450 3A activity.
  94. (1979). Interaction between NADPHcytochrome P-450 reductase and cytochrome P-450 in the membrane of phosphatidylcholine vesicles.
  95. (1985). Interaction of cytochrome P-450 with a hydroperoxide derived from butylated hydroxytoluene. Mechanism of isomerization.
  96. (1991). Interactions among cytochromes P-450 in the endoplasmic reticulum. Detection of chemically cross-linked complexes with monoclonal antibodies.
  97. (1998). Interactions among P450 enzymes when combined in reconstituted systems: formation of a 2B4-1A2 complex with a high affinity for NADPH-cytochrome P450 reductase.
  98. (1980). Interactions of cytochrome P-450, NADPH-cytochrome P-450 reductase, phospholipid, and substrate in the reconstituted liver microsomal enzyme system.
  99. (1996). Interactions of cytochrome P450 2B4 with NADPH-cytochrome P450 reductase studied by fluorescent probe.
  100. (2003). Interflavin electron transfer in human cytochrome P450 reductase is enhanced by coenzyme binding - Relaxation kinetic studies with coenzyme analogues.
  101. (1994). Investigation of the Rate-Limiting Step for Electron-Transfer from Nadph -Cytochrome-P450 Reductase to Cytochrome-B(5) - a Laser Flash-Photolysis Study.
  102. (2005). Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6.
  103. (1994). Kinetic mechanism for the model reaction of NADPH-cytochrome P450 oxidoreductase with cytochrome c.
  104. (2005). Kinetics of Dithionite-Dependent Reduction of Cytochrome P450 3A4: Heterogeneity of the Enzyme Caused by Its Oligomerization.
  105. (1983). Kinetics of elementary steps in the cytochrome P-450 reaction sequence. V. Laser temperature-jump investigation of the spin relaxation kinetics of cytochrome P-450 LM2.
  106. (1983). Kinetics of elementary steps in the cytochrome P-450 reaction sequence. VI. Model treatment of the NADPH-dependent first electron transfer reaction between cytochrome P-450 reductase and cytochrome P450 LM2 in solution.
  107. (1997). Kinetics of ferric cytochrome P450 reduction by NADPH-cytochrome P450 reductase: rapid reduction in the absence of substrate and variations among cytochrome P450 systems.
  108. (1982). Kinetics of hepatic cytochrome P-450 reduction: correlation with spin state of the ferric heme.
  109. (1979). Kinetics of reduction of cytochrome P-450LM4 in a reconstituted liver microsomal enzyme system.
  110. (1996). Lack of electron transfer from cytochrome b5 in stimulation of catalytic activities of cytochrome P450 3A4. Characterization of a reconstituted cytochrome P450 3A4/NADPH-cytochrome P450 reductase system and studies with apo-cytochrome b5.
  111. (1997). Liposomes in gene delivery.
  112. (2000). Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity.
  113. (1971). Mechanism of cholestasis. 3. Interaction of synthetic detergents with the
  114. (1984). Mechanism of rate control of the NADPH-dependent reduction of cytochrome P-450 by lipids in reconstituted phospholipid vesicles.
  115. (2003). Membrane properties induced by anionic phospholipids and phosphatidylethanolamine are critical for the membrane binding and catalytic activity of human cytochrome P450 3A4.
  116. (2006). Mitochondrial P450s.
  117. (1988). Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by alpha-naphthoflavone.
  118. (1993). Molecular evolution of P450 superfamily and P450-containing monooxygenase systems.
  119. (1990). Molecular genetics of the P-450 superfamily.
  120. (2008). Multiple substrate binding by cytochrome P450 3A4: estimation of the number of bound substrate molecules. Drug Metab Dispos.
  121. (2003). Multisite kinetic analysis of interactions between prototypical CYP3A4 subgroup substrates: midazolam, testosterone, and nifedipine.
  122. (1995). N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors.
  123. (1979). NADPH reduction of cytochrome P-450 at different integrational levels of the enzyme system.
  124. (1999). Natural engineering principles of electron tunnelling in biological oxidation-reduction.
  125. (2003). New perspectives on the conformational equilibrium regulating multi-phasic reduction of cytochrome P450 2B4 by cytochrome P450 reductase.
  126. (1995). Nitric oxide synthases: properties and catalytic mechanism.
  127. (2005). Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed reactions.
  128. (1971). On the inhibitory action of mersalyl on microsomal drug oxidation: a rigid organization of the electron transport chain.
  129. (1984). On the mechanism of action of cytochrome P-450. Oxidation and reduction of the ferrous dioxygen complex of liver microsomal cytochrome P-450 by cytochrome b5.
  130. (2003). Organization of multiple cytochrome P450s with NADPH-cytochrome P450 reductase in membranes.
  131. (1998). Oxidation of nonionic detergents by cytochrome P450 enzymes.
  132. (1983). Oxidation-reduction properties of rat liver cytochromes P-450 and NADPH-cytochrome p-450 reductase related to catalysis in reconstituted systems.
  133. (1996). P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature.
  134. (2010). P450cam visits an open conformation in the absence of substrate.
  135. (2008). Physical incorporation of NADPH-cytochrome P450 reductase and cytochrome P450 into phospholipid vesicles using glycocholate and Bio-Beads. Drug Metab Dispos,
  136. (1958). Pigments of rat liver microsomes.
  137. (2002). Polymorphism of cytochrome P450 and xenobiotic toxicity.
  138. (2001). Predicting drug pharmacokinetics in humans from in vitro metabolism studies.
  139. (2003). Preparation and characterisation of P450 3A4,
  140. (1979). Properties of NADPH-cytochrome P-450 reductase purified from rabbit liver microsomes.
  141. (1987). Protein-protein and lipid-protein interactions in a reconstituted cytochrome P-450 dependent microsomal monooxygenase.
  142. (1978). Purified liver microsomal NADPH-cytochrome P-450 reductase. Spectral characterization of oxidation-reduction states.
  143. (2004). Radical rebound mechanism in cytochrome P450-catalyzed hydroxylation of the multifaceted radical clocks alpha- and beta-thujone.
  144. (2002). Rate-limiting steps in cytochrome P450 catalysis.
  145. (1996). Reaction of cytochrome P450 with cumene hydroperoxide: ESR spin-trapping evidence for the homolytic scission of the peroxide O-O bond by ferric cytochrome P450 1A2.
  146. (1974). Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds and endogenous substrates. VII. Stimulation of benzphetamine N-demethylation by lipid and detergent.
  147. (2003). Reconstitution of membrane proteins into liposomes.
  148. (1997). 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.
  149. (2007). Redox Potential Control by Drug Binding to Cytochrome P450 3A4.
  150. (1989). Regulation mechanisms of the activity of the hepatic endoplasmic cytochrome p450 In
  151. (1992). Relationship between the rate of reductasecytochrome P450 complex formation and the rate of first electron transfer.
  152. (2002). Relaxation kinetics of cytochrome P450 reductase: internal electron transfer is limited by conformational change and regulated by coenzyme binding.
  153. (1969). Resolution of the cytochrome P-450-containing omega-hydroxylation system of liver microsomes into three components.
  154. (1994). Resonance Raman spectroscopy of the catalytic intermediates and derivatives of chloroperoxidase from Caldariomyces fumago.
  155. (1995). Role of acidic residues in the interaction of NADPH-cytochrome P450 oxidoreductase with cytochrome P450 and cytochrome c.
  156. (2005). Role of cytochrome B5 in modulating peroxide-supported cyp3a4 activity: evidence for a conformational transition and cytochrome P450 heterogeneity.
  157. (2001). Role of LYS271 and LYS279 residues in the interaction of cytochrome P4501A1 with NADPH-cytochrome P450 reductase.
  158. (1992). Role of phospholipids in reconstituted cytochrome P450 3A form and mechanism of their activation of catalytic activity.
  159. (1984). Role of the electron transfer system in microsomal drug monooxygenase reaction catalyzed by cytochrome P-450.
  160. (1996). Roles of cytochrome b5 in the oxidation of testosterone and nifedipine by recombinant cytochrome P450 3A4 and by human liver microsomes.
  161. (1995). Roles of divalent metal ions in oxidations catalyzed by recombinant cytochrome P450 3A4 and replacement of NADPH--cytochrome P450 reductase with other flavoproteins, ferredoxin, and oxygen surrogates.
  162. (2002). Roles of NADPH-P450 reductase and apo- and holo-cytochrome b5 on xenobiotic oxidations catalyzed by 12 recombinant human cytochrome P450s expressed in membranes of Escherichia coli.
  163. (1982). Rotation of cytochrome P-450. I. Investigations of protein-protein interactions of cytochrome P-450 in phospholipid vesicles and liver microsomes.
  164. (1982). Rotation of cytochrome P-450. II. Specific interactions of cytochrome P-450 with NADPHcytochrome P-450 reductase in phospholipid vesicles.
  165. (1981). Separate roles for FMN and FAD in catalysis by liver microsomal NADPH-cytochrome P-450 reductase.
  166. (2006). Shriver and Atkins' inorganic chemistry Sligar,
  167. (1976). Some properties of a detergent-solubilized NADPH-cytochrome c(cytochrome P-450) reductase purified by biospecific affinity chromatography.
  168. (1973). Some properties of hepatic reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase.
  169. (1967). Spectral studies of drug interaction with hepatic microsomal cytochrome.
  170. (1992). Speculations on the substrate structure-activity relationship (SSAR) of cytochrome P450 enzymes.
  171. (1973). Spin labels as enzyme substrates. Heterogeneous lipid distribution in liver microsomal membranes.
  172. (1979). Spin state control of the hepatic cytochrome P450 redox potential.
  173. (1979). Spin transition of camphor-bound cytochrome P-450. 2. Kinetics following rapid changes of the local paH at sub-zero temperatures.
  174. (2001). Stimulation of cytochrome P450 reactions by apo-cytochrome b5: evidence against transfer of heme from cytochrome P450 3A4 to apo-cytochrome b5 or heme oxygenase.
  175. (2001). Stoppedflow kinetic studies of flavin reduction in human cytochrome P450 reductase and its component domains.
  176. (1989). Structural analysis of the FMN binding domain of NADPH-cytochrome P-450 oxidoreductase by site-directed mutagenesis.
  177. (2006). Structural basis for ligand promiscuity in cytochrome P450 3A4.
  178. (2005). Structure and chemistry of cytochrome P450.
  179. (2009). Structure and function of an NADPH-cytochrome P450 oxidoreductase in an open conformation capable of reducing cytochrome P450.
  180. (2005). Structures of cytochrome P450 enzymes.
  181. (1979). Studies on the association of cytochrome P-450 and NADPH-cytochrome c reductase during catalysis in a reconstituted hydroxylating system.
  182. (1981). Substrate interaction with cytochrome P-450.
  183. (1995). Substrate-dependent competition of different P450 isozymes for limiting NADPH-cytochrome P450 reductase.
  184. (2002). Summary of information on human CYP enzymes: human P450 metabolism data.
  185. (1976). Temperature dependence of cytochrome P-450 reduction. A model for NADPHcytochrome P-450 reductase:cytochrome P-450 interaction.
  186. (1985). The 2.6-A crystal structure of Pseudomonas putida cytochrome P-450.
  187. (1975). The association between cytochrome P-450 and NADPH-cytochrome P-450 reductase in microsomal membrane.
  188. (1984). The association of cytochrome P-450 and NADPHcytochrome P-450 reductase in phospholipid membranes.
  189. (1973). The binding of riboflavin-5'-phosphate in a flavoprotein: flavodoxin at 2.0-Angstrom resolution.
  190. (1964). The Carbon Monoxide-Binding Pigment of Liver Microsomes. I. Evidence for Its Hemoprotein Nature.
  191. (2000). The catalytic pathway of cytochrome p450cam at atomic resolution.
  192. (1992). The cytochrome P450 2B4-NADPH cytochrome P450 reductase electron transfer complex is not formed by charge-pairing.
  193. (1980). The effect of microsomal fatty acids and other lipids on the spin state of partially purified cytochrome P-450.
  194. (1988). The effect of NADPH concentration on the reduction of cytochrome P-450 LM2.
  195. (1995). The effects of cytochrome b5, NADPH-P450 reductase, and lipid on the rate of 6 betahydroxylation of testosterone as catalyzed by a human P450 3A4 fusion protein.
  196. (2006). The ferrous-dioxygen intermediate in human cytochrome P450 3A4. Substrate dependence of formation and decay kinetics.
  197. (1977). The low-spin/high-spin transition equilibrium of camphor-bound cytochrome P-450. Effects of medium and temperature on equilibrium data.
  198. (2003). The many roles of cytochrome b5.
  199. (1992). The role of cytochrome P450 and cytochrome P450 reductase in the reductive bioactivation of the novel benzotriazine diN-oxide hypoxic cytotoxin 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233, WIN 59075) by mouse liver.
  200. (1996). The role of cytochrome P450 monooxygenases in plant-insect interactions.
  201. (1995). The stoichiometry of the cytochrome P-450-catalyzed metabolism of methoxyflurane and benzphetamine in the presence and absence of cytochrome b5.
  202. (2004). The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution.
  203. (2004). The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-angstrom resolution.
  204. (2005). The thermodynamic landscape of testosterone binding to cytochrome P450 3A4: ligand binding and spin state equilibria.
  205. (1997). Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes.
  206. (1980). Visible and ultraviolet spectral transitions of camphor-bound cytochrome P-450. A comprehensive study.
  207. (2007). What common structural features and variations of mammalian P450s are known to date?
  208. (1987). Zwitterionic detergent mediated interaction of purified cytochrome P-450LM4 from 5,6-benzoflavone-treated rabbits with MADPH-cytochrome P-450 reductase.

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