CYP2C9-CYP3A4 protein-protein interactions: Role of the hydrophobic N terminus

Drug Metabolism and Disposition

Volumn 38, Issue 6, 2010, Pages 1003-1009

  Subramanian, Murali ^a   Tam, Harrison ^a   Zheng, Helen ^a   Tracy, Timothy S ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; FLURBIPROFEN; NAPROXEN; TESTOSTERONE;

AMINO TERMINAL SEQUENCE; ARTICLE; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SUBSTRATE COMPLEX; HUMAN; HYDROPHOBICITY; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION;

AMINO ACID SEQUENCE; ANIMALS; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP3A; HUMANS; HYDROPHOBICITY; MALE; REPRESSOR PROTEINS;

EID: 77952304154     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.109.030155     Document Type: Article

References (47)

1. Alston K, Robinson RC, Park SS, Gelboin HV, and Friedman FK (1991) Interactions among cytochromes P-450 in the endoplasmic reticulum. Detection of chemically cross-linked complexes with monoclonal antibodies. J Biol Chem 266:735-739. (Pubitemid 21907176)
2. Backes WL, Batie CJ, and Cawley GF (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. Biochemistry 37:12852-12859.
3. Backes WL and Cawley GF (1999) Interactions among NADPH-cytochrome P450 reductase, P450 1A1, and P450 2B4. FASEB J 13:A811.
4. Backes WL and Kelley RW (2003) Organization of multiple cytochrome P450s with NADPH-cytochrome P450 reductase in membranes. Pharmacol Ther 98:221-233.
5. Barnes HJ, Arlotto MP, and Waterman MR (1991) Expression and enzymatic activity of recombinant cytochrome P450 17 alpha-hydroxylase in Escherichia coli. Proc Natl Acad Sci USA 88:5597-5601. (Pubitemid 21914792)
6. Black SD, French JS, Williams CH Jr, and Coon MJ (1979) Role of a hydrophobic polypeptide in the N-terminal region of NADPH-cytochrome P-450 reductase in complex formation with P-450LM. Biochem Biophys Res Commun 91:1528-1535.
7. Black SD and Martin ST (1994) Evidence for conformational dynamics and molecular aggregation in cytochrome P450 102 (BM-3). Biochemistry 33:12056-12062.
8. Bridges A, Gruenke L, Chang YT, Vakser IA, Loew G, and Waskell L (1998) Identification of the binding site on cytochrome P450 2B4 for cytochrome b5 and cytochrome P450 reductase. J Biol Chem 273:17036-17049. (Pubitemid 28311737)
9. Cawley GF, Batie CJ, and Backes WL (1995) Substrate-dependent competition of different P450 isozymes for limiting NADPH-cytochrome P450 reductase. Biochemistry 34:1244-1247.
10. Cawley GF, Zhang S, Kelley RW, and Backes WL (2001) Evidence supporting the interaction of CYP2B4 and CYP1A2 in microsomal preparations. Drug Metab Dispos 29:1529-1534. (Pubitemid 33111584)
11. Chudaev MV, Gilep AA, and Usanov SA (2001) Site-directed mutagenesis of cytochrome b5 for studies of its interaction with cytochrome P450. Biochemistry-Moscow 66:667-681. (Pubitemid 32699928)
12. Davydov DR, Fernando H, Baas BJ, Sligar SG, and Halpert JR (2005) Kinetics of dithionite-dependent reduction of cytochrome P450 3A4: heterogeneity of the enzyme caused by its oligomerization. Biochemistry 44:13902-13913. (Pubitemid 41507470)
13. Fisher CD, Lickteig AJ, Augustine LM, Ranger-Moore J, Jackson JP, Ferguson SS, and Cherrington NJ (2009) Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab Dispos 37:2087-2094.
14. French JS, Guengerich FP, and Coon MJ (1980) Interactions of cytochrome P-450, NADPHcytochrome P-450 reductase, phospholipid, and substrate in the reconstituted liver microsomal enzyme system. J Biol Chem 255:4112-4119.
15. Gillam EM, Baba T, Kim BR, Ohmori S, and Guengerich FP (1993) Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. Arch Biochem Biophys 305:123-131. (Pubitemid 23242002)
16. Guengerich FP (2002) Rate-limiting steps in cytochrome P450 catalysis. Biol Chem 383:1553-1564.
17. Guengerich FP (2006) Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J 8:E101-E111.
18. Guengerich FP and Holladay LA (1979) Hydrodynamic characterization of highly purified and functionally active liver microsomal cytochrome P-450. Biochemistry 18:5442-5449.
19. Hazai E, Bikádi Z, Simonyi M, and Kupfer D (2005) Association of cytochrome P450 enzymes is a determining factor in their catalytic activity. J Comput Aided Mol Des 19:271-285. (Pubitemid 41386822)
20. Hazai E and Kupfer D (2005) Interactions between CYP2C9 and CYP2C19 in reconstituted binary systems influence their catalytic activity: possible rationale for the inability of CYP2C19 to catalyze methoxychlor demethylation in human liver microsomes. Drug Metab Dispos 33:157-164. (Pubitemid 40023527)
21. Jungermann K (1995) Zonation of metabolism and gene expression in liver. Histochem Cell Biol 103:81-91.
22. Kaminsky LS and Guengerich FP (1985) Cytochrome P-450 isozyme/isozyme functional interactions and NADPH-cytochrome P-450 reductase concentrations as factors in microsomal metabolism of warfarin. Eur J Biochem 149:479-489.
23. Kelley RW, Cheng D, and Backes WL (2006) Heteromeric complex formation between CYP2E1 and CYP1A2: evidence for the involvement of electrostatic interactions. Biochemistry 45: 15807-15816. (Pubitemid 46032501)
24. Kelley RW, Reed JR, and Backes WL (2005) Effects of ionic strength on the functional interactions between CYP2B4 and CYP1A2. Biochemistry 44:2632-2641.
25. Kempf AC, Zanger UM, and Meyer UA (1995) Truncated human P450 2D6: expression in Escherichia coli, Ni(2+)-chelate affinity purification, and characterization of solubility and aggregation. Arch Biochem Biophys 321:277-288.
26. Kimzey AL, Weitz KK, Guengerich FP, and Zangar RC (2003) Hydroperoxy-10,12-octadecadienoic acid stimulates cytochrome P450 3A protein aggregation by a mechanism that is inhibited by substrate. Biochemistry 42:12691-12699.
27. Lee-Robichaud P, Kaderbhai MA, Kaderbhai N, Wright JN, and Akhtar M (1997) Interaction of human CYP17 (P-450(17alpha), 17alpha-hydroxylase-17,20- lyase) with cytochrome b5: importance of the orientation of the hydrophobic domain of cytochrome b5. Biochem J 321: 857-863. (Pubitemid 27084898)
28. Li DN, Pritchard MP, Hanlon SP, Burchell B, Wolf CR, and Friedberg T (1999) Competition between cytochrome P-450 isozymes for NADPH-cytochrome P-450 oxidoreductase affects drug metabolism. J Pharmacol Exp Ther 289:661-667.
29. Locuson CW, Gannett PM, and Tracy TS (2006) Heteroactivator effects on the coupling and spin state equilibrium of CYP2C9. Arch Biochem Biophys 449:115-129.
30. Locuson CW, Wienkers LC, Jones JP, and Tracy TS (2007) CYP2C9 protein interactions with cytochrome b(5): effects on the coupling of catalysis. Drug Metab Dispos 35:1174-1181.
31. Matsuura S, Fujii-Kuriyama Y, and Tashiro Y (1978) Immunoelectron microscope localization of cytochrome P-450 on microsomes and other membrane structures of rat hepatocytes. J Cell Biol 78:503-519.
32. Mulrooney SB, Meinhardt DR, and Waskell L (2004) The alpha-helical membrane spanning domain of cytochrome b5 interacts with cytochrome P450 via nonspecific interactions. Biochim Biophys Acta 1674:319-326.
33. Myasoedova KN and Tsuprun VL (1993) Cytochrome P-450: hexameric structure of the purified LM4 form. Febs Lett 325:251-254.
34. Oinonen T and Lindros KO (1998) Zonation of hepatic cytochrome P-450 expression and regulation. Biochem J 329:17-35.
35. Omata Y, Sakamoto H, Robinson RC, Pincus MR, and Friedman FK (1994) Interaction between cytochrome P450 2B1 and cytochrome bs: inhibition by synthetic peptides indicates a role for P450 residues Lys-122 and Arg-125. Biochem Biophys Res Commun 201:1090-1095.
36. Ozalp C, Szczesna-Skorupa E, and Kemper B (2005) Bimolecular fluorescence complementation analysis of cytochrome P450 2C2, 2E1, and NADPH-cytochrome P450 reductase molecular interactions in living cells. Drug Metab Dispos 33:1382-1390.
37. Shen S and Strobel HW (1993) Role of lysine and arginine residues of cytochrome P450 in the interaction between cytochrome P4502B1 and NADPH-cytochrome P450 reductase. Arch Biochem Biophys 304:257-265.
38. Shimada T, Mernaugh RL, and Guengerich FP (2005) Interactions of mammalian cytochrome P450, NADPH-cytochrome P450 reductase, and cytochrome b(5) enzymes. Arch Biochem Biophys 435:207-216.
39. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423.
40. Shimizu T, Tateishi T, Hatano M, and Fujii-Kuriyama Y (1991) Probing the role of lysines and arginines in the catalytic function of cytochrome P450d by site-directed mutagenesis. Interaction with NADPH-cytochrome P450 reductase. J Biol Chem 266:3372-3375.
41. Subramanian M, Low M, Locuson CW, and Tracy TS (2009) CYP2D6-CYP2C9 protein-protein interactions and isoform-selective effects on substrate binding and catalysis. Drug Metab Dispos 37:1682-1689.
42. Szczesna-Skorupa E and Kemper B (2008) Influence of protein-protein interactions on the cellular localization of cytochrome P450. Expert Opin Drug Metab Toxicol 4:123-136.
43. Tan Y, Patten CJ, Smith T, and Yang CS (1997) Competitive interactions between cytochromes P450 2A6 and 2E1 for NADPH-cytochrome P450 oxidoreductase in the microsomal membranes produced by a baculovirus expression system. Arch Biochem Biophys 342:82-91.
44. Tracy TS, Hutzler JM, Haining RL, Rettie AE, Hummel MA, and Dickmann LJ (2002) Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: effect on atypical kinetic metabolism profiles. Drug Metab Dispos 30:385-390.
45. Tracy TS, Marra C, Wrighton SA, Gonzalez FJ, and Korzekwa KR (1997) Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur J Clin Pharmacol 52:293-298.
46. Tsuprun VL, Myasoedova KN, Berndt P, Sograf ON, Orlova EV, Chernyak VYa, Archakov AI, and Skulachev VP (1986) Quaternary structure of the liver microsomal cytochrome P-450. FEBS Lett 205:35-40.
47. Yamazaki H, Gillam EM, Dong MS, Johnson WW, Guengerich FP, and Shimada T (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. Arch Biochem Biophys 342:329-337.