Mechanistic enzymology of oxygen activation by the cytochromes P450

Drug Metabolism Reviews

Volumn 34, Issue 4, 2002, Pages 691-708

  Makris, Thomas M ^a   Davydov, Roman ^c   Denisov, Ilia G ^b   Hoffman, Brian M ^c   Sligar, Stephen G ^a,b  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^b UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^c NORTHWESTERN UNIVERSITY   (United States)

Author keywords

CYP101; ENDOR spectra; EPR spectra; Monooxygenase; P450; Peroxo ferric intermediate; Radiolytic reduction; UV Vis spectra; X ray crystallography

Indexed keywords

5 HYDROXYCAMPHOR; ALANINE; CAMPHOR; CYTOCHROME; CYTOCHROME P450; HYDROGEN PEROXIDE; PYRIDINE NUCLEOTIDE; THREONINE; UNCLASSIFIED DRUG; OXYGEN;

AMINO ACID COMPOSITION; AMINO ACID SEQUENCE; CATALYSIS; CHEMICAL MUTAGENESIS; CHEMICAL REACTION; CRYOBIOLOGY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; ELECTRON TRANSPORT; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME ISOLATION; ENZYME MECHANISM; HYDROGEN BOND; HYDROXYLATION; MASS SPECTROMETRY; MODEL; MOLECULAR DYNAMICS; MUTATION; OXYGEN AFFINITY; PH; PROTON TRANSPORT; RADIOLYSIS; REVIEW; SPECTROSCOPY; STRUCTURE ANALYSIS; TITRIMETRY; WILD TYPE; ANIMAL; CHEMISTRY; HUMAN; METABOLISM; OXIDATION REDUCTION REACTION;

ANIMALS; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; OXIDATION-REDUCTION; OXYGEN;

EID: 1842842895     PISSN: 03602532     EISSN: None     Source Type: Journal    
DOI: 10.1081/DMR-120015691     Document Type: Review

References (68)

1. Sligar, S.G. Nature's universal oxygenases: The cytochromes P450. Essays Biochem. 1999, 34, 71-83.
2. Guengerich, F.P. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 2001, 14, 611-650.
3. Brewer, C.B.; Peterson, J.A. Single turnover kinetics of the reaction between oxycytochrome P-450cam and reduced putidaredoxin. J. Biol. Chem. 1988, 263, 791-798.
4. Tsai, R.; Yu, C.-A.; Gunsalus, I.C.; Peisach, J.; Blumberg, W.E.;Orme-Johnson, W.H.; Beinert, H. Spin-state changes in cytochrome P-450cam on binding of specific substrates. Proc. Natl. Acad. Sci. USA 1970, 66, 1157-1163.
5. Sligar, S.G. Coupling of spin, substrate, and redox equilibria in cytochrome P450. Biochemistry 1976, 15, 5399-5406.
6. Fisher, M.T.; Sligar, S.G. Control of heme protein redox potential and reduction rates: Linear free energy relationships between potential and ferric spin state equilibrium. J. Am. Chem. Soc. 1985, 107, 5018-5019.
7. Sibbeson, O.; Zhang, Z.; Ortiz de Montellano, P.R. Cytochrome P450cam substrate specificity: Relationship between structure and catalytic oxidation of alkylbenzenes. Arch. Biochem. Biophys. 1998, 353, 285-296.
8. Gould, P.; Gelb, M.H.; Sligar, S.G. Interaction of 5-bromocamphor with cytochrome P-450cam. J. Biol. Chem. 1981, 256, 6686-6691.
9. Sharrock, M.; Debrunner, P.G.; Schulz, C.; Lipscomb, J.D.; Marshall, V.; Gunsalus, I.C. Cytochrome P450cam and its complexes. Mossbauer parameters of the heme iron. Biochim. Biophys. Acta 1976, 420, 8-26.
10. Champion, P.M.; Gunsalus, I.C.; Wagner, G.C. Resonance Raman investigations of cytochrome P450cam from Pseudomonas putida. J. Am. Chem. Soc. 1978, 100, 3743-3751.
11. Macdonald, I.D.G.; Sligar, S.G.; Christian, J.F.; Unno, M.; Champion, P.M. Identification of the Fe - O - O bending mode in oxycytochrome P450cam by resonance Raman spectroscopy. J. Am. Chem. Soc. 1999, 121, 376-380.
12. Katagiri, M.; Ganguli, B.N.; Gunsalus, I.C. A Soluble cytochrome P-450 functional in methylene hydroxylation. J. Biol. Chem. 1968, 243, 3543-3546.
13. Schulz, C.E.; Rutter, R.; Sage, J.T.; Debrunner, P.G.; Hager, L.P. Mossbauer and electron paramagnetic resonance studies of horseradish peroxidase and its catalytic intermediates. Biochemistry 1984, 23, 4743-4754.
14. Poulos, T.L.; Kraut, J. The stereochemistry of peroxidase catalysis. J. Biol. Chem. 1980, 255, 8199-8205.
15. Harris, D.L.; Loew, G.H. Investigation of the proton-assisted pathway to formation of the catalytically active, ferryl species of P450s by molecular dynamics studies of P450eryF. J. Am. Chem. Soc. 1996, 118 (27), 6377-6387.
16. Groves, J.T.; McClusky, G.A. Aliphatic hydroxylation via oxygen rebound. Oxygen transfer catalyzed by iron. J. Am. Chem. Soc. 1976, 98, 859-861.
17. Dolphin, D.; James, B.R.; Welborn, H.C. Proton activities for three states of cytochrome P-450cam. Biochem. Biophys. Res. Commun. 1979, 88, 415-421.
18. Finzel, B.C.; Poulos, T.L.; Kraut, J. Crystal structure of yeast cytochrome c peroxidase refined at 1.7-angstrom resolution. J. Biol. Chem. 1984, 259, 13027-13036.
19. Poulos, T.L.; Edwards, S.L.; Wariishi, H.; Gold, M.G. Crystallographic refinement of lignin peroxidase at 2A. J. Biol. Chem. 1993, 268, 4429-4440.
20. Poulos, T.L.; Finzel, B.C.; Gunsalus, I.C.; Wagner, G.C.; Kraut, J. The 2.6angstrom crystal structure of Pseudomonas putida cytochrome P-450. J. Biol. Chem. 1985, 260, 16122-16130.
21. Okamoto, N.; Imai, Y.; Shoun, H.; Shiro, Y. Site-directed mutagenesis of the conserved threonine (Thr243) at distal helix of fungal cytochrome P450nor. Biochemistry 1998, 37, 8839-8847.
22. Yeom, H.; Sligar, S.G.; Poulos, T.; Fulco, A. The role of Thr268 in the oxygen activation of cytochrome BM-3. Biochemistry 1995, 34, 14733-14740.
23. Yanagita, K.; Sagami, I.; Daff, S.; Shimizu, T. Marked enhancement in the reductive dehalogenation of hexachloroethane by a Thr319Ala mutation of cytochrome P450 1A2. Biochem. Biophys. Res. Commun. 1998, 249, 678-682.
24. Nitahara, Y.; Kishimoto, K.; Yabusaki, Y.; Gotoh, O.; Yoshida, Y.; Horiuchi, Y.; Aoyama, Y. The amino acid residues affecting the activity and azole susceptibility of rat cyp51. J. Biochem. 2001, 129, 761-768.
25. Kao, Y.C.; Korzekwa, K.R.; Laughton, C.A.; Chen, S. Evaluation of the mechanism of aromatase cytP450. Eur. J. Biochem. 2001, 268, 243-251.
26. Roussel, F.; Khan, K.K.; Halpert, J.R. The importance of srs-1 residues in catalytic specificity of cytochrome P450 3A4. Arch. Biochem. Biophys. 2000, 374, 269-278.
27. Coon, M.J.; Vaz, A.D.N.; McGinnity, D.F.; Peng, H.M. Multiple oxygen species in P450 catalysis. Drug Metab. Dispos. 1998, 26, 1190-1193.
28. Imai, Y.; Nakamura, M. Point mutations at threonine-301 modify substrate specificity of rabbit liver microsomal cytochromes P-450 (laurate (omega-1)hydroxylase and testosterone 16 alpha-hydroxylase). Biochem. Biophys. Res. Commun. 1989, 158, 717-722.
29. Imai, M.; Shimada, H.; Watanabe, Y.; Matsushima-Hibiya, Y.; Makino, R.; Koga, H.; Horiuchi, T.; Ishimura, Y. Uncoupling of the cytochrome P-450cam monooxygenase reaction by a single mutation, threonine-252 to alanine or valine: A possible role of the hydroxy amino acid in oxygen activation. Proc. Natl. Acad. Sci. USA 1989, 86, 7823-7827.
30. Martinis, S.A.; Atkins, W.M.; Stayton, P.S.; Sligar, S.G. A conserved residue of cytochrome P-450 is involved in heme-oxygen stability and activation. J. Am. Chem. Soc. 1989, 111, 9252-9253.
31. Raag, R.; Martinis, S.A.; Sligar, S.G.; Poulos, T.L. Crystal structure of the cytochrome P-450cam active site mutant Thr252Ala. Biochemistry 1991, 30, 11420-11429.
32. Shimada, H.; Watanabe, Y.; Imai, M.; Makino, R.; Koga, H.; Horiuchi, T.; Ishimura, Y. The role of threonine 252 in oxygen activation by cytochrome P-450cam: Mechanistic studies by site-directed mutagenesis. In Dioxygen Activation and Homogeneous Catalytic Oxidation; Simandi, L.I., Ed.; Elsevier Science Publishers: Amsterdam, 1991; 313-319.
33. Shimada, H.; Makino, R.; Unno, M.; Horiuchi, T.; Ishimura, Y. Proton and electron transfer mechanism in dioxygen activation by cytochrome P450cam. 8th Cytochrome P450 Int. Conf., Paris, France, 1993; Lechner, M.C., Eds.; Libbey: Montrouge, 1994; 299-306.
34. Kimata, Y.; Shimada, H.; Hirose, T.; Ishimura, Y. Role of Thr-252 in cytochrome P450cam: A study with unnatural amino acids. Biochem. Biophys. Res. Commun. 1995, 208, 96-102.
35. Shafiee, A.; Hutchinson, C.R. Macrolide antibiotic biosynthesis: Isolation and properties of two forms of 6-deoxyerythronolide B hydroxylase from Saccharopolyspora erythraea (Streptomyces erythreus). Biochemistry 1987, 26, 6204-6210.
36. Shafiee, A.; Hutchinson, C.R. Purification and reconstitution of the electron transport components for 6-deoxyerythronolide B hydroxylase, a cytochrome P450 enzyme of macrolide antibiotic (erythromycin) biosynthesis. J. Bacteriol. 1988, 170, 1548-1553.
37. Cupp-Vickery, J.R.; Poulos, T.L. Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Nat. Struct. Biol. 1995, 2, 144-153.
38. Cupp-Vickery, J.R.; Han, O.; Hutchinson, C.R.; Poulos, T.L. Substrate-assisted catalysis in cytochrome P450eryF. Nat. Struct. Biol. 1996, 3, 632-637.
39. Andersen, J.F.; Tatsuta, K.; Gunji, H.; Ishiyama, T.; Hutchinson, C.R. Substrate specificity of 6-deoxyerythronolide B hydroxylase, a bacteria cytochrome P450 of erythromycin A biosynthesis. Biochemistry 1993, 32, 1905-1913.
40. Xiang, H.; Tschirret-Guth, R.A.; de Montellano, P.R.O. An A245T Mutation Conveys the P450eryf to Oxidize Alternative Substrates. 2000, 275, 35999-36006.
41. Ishigooka, M.; Shimizu, T.; Hiroya, K.; Hatano, M. Role of Glu318 at the putative distal site in the catalytic function of cytochrome P450d. Biochemistry 1992, 31, 1528-1531.
42. Amarneh, B.; Corbin, C.J.; Peterson, J.A.; Simpson, E.R.; Graham-Lorence, S. Functional domains of human aromatase cytochrome P450 characterized by linear alignment and site-directed mutagenesis. Mol. Endocrinol. 1993, 7, 1617-1624.
43. Gerber, N.C.; Sligar, S.G. Catalytic mechanism of cytochrome P-450: Evidence for a distal charge relay. J. Am. Chem. Soc. 1992, 114, 8742-8743.
44. Benson, D.E.; Suslick, K.S.; Sligar, S.G. Reduced oxy intermediate observed in D251N cytochrome P450cam. Biochemistry 1997, 36, 5104-5107.
45. Vidakovic, M.; Sligar, S.G.; Li, H.; Poulos, T.L. Understanding the role of the essential Asp251 in cytochrome P450cam using site-directed mutagenesis, crystallography, and kinetic solvent isotope effect. Biochemistry 1998, 37, 9211-9219.
46. Gerber, N.C.; Sligar, S.G. A role for Asp-251 in cytochrome P-450cam oxygen activation. J. Biol. Chem. 1994, 269, 4260-4266.
47. Aikens, J.; Sligar, S.G. Kinetic solvent isotope effects during oxygen activation by cytochrome P-450cam. J. Am. Chem. Soc. 1994, 116, 1143-1144.
48. Schowen, R.L. Solvent isotope effects on enzymic reactions. In Isotope Effects on Enzyme-Catalyzed Reactions; Cleland, W.W., O'Leary, M.H., Northrop, D.B., Eds.; University Park Press: Baltimore, 1977; 64-99.
49. Turner, J.J.; Pimentel, G.C. Krypton fluoride: Preparation by the matrix isolation technique. Science 1963, 140, 974-975.
50. Symons, M.C.R.; Petersen, R.L. Electron capture by oxyhemoglobin: An ESR study. Proc. R. Soc. London B 1978, 201, 285-300.
51. Davydov, R.M. Optical and ESR spectroscopic studies of electron adducts of oxymyoglobin and oxyhemoglobin. Biofizika 1980, 25, 203-207.
52. 2] -[ferrite] center from irradiated oxyhemo- and oxymyoglobin. Biochim. Biophys. Acta 1985, 827, 327-343.
53. Davydov, R.; Kuprin, S.; Graslund, A.; Ehrenberg, A. Electron paramagnetic resonance study of the mixed-valent diiron center in escherichia coli ribonucleotide reductase produced by reduction of radical-free protein R2 at 77K. J. Am. Chem. Soc. 1994, 116, 11120-11128.
54. Davydov, R.; Kappl, R.; Hutterman, R.; Peterson, J.A. EPR-spectroscopy of reduced oxyferrous-P450cam. FEBS Lett. 1991, 295, 113-115.
55. Davydov, R.; Macdonald, I.D.G.; Makris, T.M.; Sligar, S.G.; Hoffman, B.M. EPR and ENDOR of catalytic intermediates in cryoreduced native and mutant oxycytochromes P450cam: Mutation-induced changes in the proton delivery system. J. Am. Chem. Soc. 1999, 121, 10654-10655.
56. Burstyn, J.N.; Roe, J.A.; Miksztal, A.R.; Shaevitz, B.A.; Lang, G.; Valentine, J.S. Magnetic and spectroscopic characterization of an iron porphyrin peroxide complex. Peroxoferrioctaethylporphyrin(1-). J. Am. Chem. Soc. 1988, 110, 1382-1388.
57. Hoffman, B.M.; Diemente, D.L.; Basolo, F. Electron paramagnetic resonance studies of some cobalt(II) schiff base compounds and their monomeric oxygen adducts. J. Am. Chem. Soc. 1970, 92, 61-65.
58. Davydov, R.; Makris, T.M.; Kofman, V.; Werst, D.E.; Sligar, S.G.; Hoffman, B.M. Hydroxylation of camphor by reduced oxy-cytochrome P450cam: Mechanistic implications of EPR and ENDOR studies of catalytic intermediates in native and mutant enzymes. J. Am. Chem. Soc. 2001, 123, 1403-1415.
59. Lipscomb, J.D. Electron paramagnetic resonance detectable states of cytochrome P-450cam. Biochemistry 1980, 19, 3590-3599.
60. White, R.E.; McCarthy, M.B.; Egeberg, K.D.; Sligar, S.G. Regioselectivity in the cytochromes P-450: Control by protein constraints and by chemical reactivities. Arch. Biochem. Biophys. 1984, 228, 493-502.
61. Newcomb, M.; Shen, R.; Choi, S.Y.; Toy, P.H.; Hollenberg, P.F.; Vaz, A.D.N.; Coon, M.J. Cytochrome P450-catalyzed hydroxylation of mechanistic probes that distinguish between radicals and cations. Evidence for cationic but not for radical intermediates. J. Am. Chem. Soc. 2000, 122, 2677-2686.
62. 3+ complex. J. Chem. Soc., Chem. Commun. 1995, 22, 2297-2298.
63. Denisov, I.G.; Makris, T.M.; Sligar, S.G. Methods in Enzymology. In press.
64. Denisov, I.G.; Makris, T.M.; Sligar, S.G. Cryotrapped reaction intermediates of cytochrome P450 studied by radiolytic reduction with phosphorus-32. J. Biol. Chem. 2001, 276, 11648-11652.
65. Harris, D.; Loew, G.; Waskell, L. Structure and spectra of ferrous dioxygen and reduced ferrous dioxygen model cytochrome P450. J. Am. Chem. Soc. 1998, 120, 4308-4318.
66. Kobayashi, K.; Amano, M.; Kanbara, Y.; Hayashi, K. One-electron reduction of the oxyform of 2,4-diacetyldeuterocytochrome P-450cam. J. Biol. Chem. 1987, 262, 5445-5447.
67. Schlichting, I.; Berendzen, J.; Chu, K.; Stock, A.M.; Maves, S.A.; Benson, D.E.; Sweet, R.M.; Ringe, D.; Petsko, G.A.; Sligar, S.G. The catalytic pathway of cytochrome P450cam at atomic resolution. Science 2000, 287, 1615-1622.
68. Yeom, H.; Sligar, S.G. Oxygen activation by cytochrome P450BM-3: Effects of mutating an active site acidic residue. Arch. Biochem. Biophys. 1997, 337, 209-216.