P450c17 mutations R347H and R358Q selectively disrupt 17,20-lyase activity by disrupting interactions with P450 oxidoreductase and cytochrome b5

Molecular Endocrinology

Volumn 13, Issue 1, 1999, Pages 167-175

  Geller, David H ^a   Auchus, Richard J ^a,b   Miller, Walter L ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME B5; CYTOCHROME P450; LYASE;

ANIMAL CELL; ARTICLE; ELECTRON TRANSPORT; ENZYME ACTIVITY; ENZYME SUBSTRATE COMPLEX; MICHAELIS CONSTANT; NONHUMAN; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; STEROIDOGENESIS;

ANIMALIA;

EID: 0032893922     PISSN: 08888809     EISSN: None     Source Type: Journal    
DOI: 10.1210/mend.13.1.0219     Document Type: Article

References (36)

1. Miller WL, Tyrrell JB 1995 The adrenal cortex. In: Felig P, Baxter J, Frohman L (eds) Endocrinology and Metabolism. McGraw Hill, New York, pp 555-717
2. 17, 20 lyase). J Biol Chem 256:3871-3876
3. 17,20 lyase cytochrome P450. J Biol Chem 259:3971-3976
4. Miller WL, Auchus RJ, Geller DH 1997 The regulation of 17,20 lyase activity. Steroids 62:135-144
5. 19 steroids by homogeneous cytochrome P-450 C21 side-chain cleavage from pig testis. Biochem Biophys Res Commun 132:708-713
6. Swart P, Swart AC, Waterman MR, Estabrook RW, Mason JI 1993 Progesterone 16α-hydroxylase activity is catalyzed by human cytochrome P450 17α-hydroxylase. J Clin Endocrinol Metab 77:98-102
7. 106 and P450 reductase. Endocrinology 132:2498-2506
8. Picado-Leonard J, Miller WL 1987 Cloning and sequence of the human gene encoding P450c17 (steroid 17α-hydroxylase/17, 20 lyase): Similarity to the gene for P450c21. DNA 6:439-448
9. Chung B, Picado-Leonard J, Haniu M, Bienkowski M, Hall PF, Shivley JE, Miller WL 1987 Cytochrome P450c17 (steroid 17α-hydroxylase/17, 20 lyase): Cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proc Natl Acad Sci USA 84:407-411
10. Yanase T, Simpson ER, Waterman MR 1991 17α-hydroxylase/17,20 lyase deficiency: From clinical investigation to molecular definition. Endocr Rev 12:91-108
11. Yanase T 1995 17α-Hydroxylase/17,20 lyase defects. J Steroid Biochem Mol Biol 53:153-157
12. Zachmann M, Vollmin JA, Hamilton W, Prader A 1972 Steroid 17,20 desmolase deficiency: A new cause of male pseudohermaphroditism. Clin Endocrinol (Oxf) 1:369-385
13. Yanase T, Waterman MR, Zachmann M, Winter JSD, Simpson ER, Kagimoto M 1992 Molecular basis of apparent isolated 17,20-lyase deficiency: Compound heterozygous mutations in the C-terminal region (Arg(496)→Cys, Gln(461)→Stop) actually cause combined 17α-hydroxylase/17,20-lyase deficiency. Biochim Biophys Acta 1139:275-279
14. Zachmann M, Kenpken B, Manella B, Navarro E 1992 Conversion from pure 17,20 desmolase to combined 17,20-desmolase/17α-hydroxylase deficiency with age. Acta Endocrinol (Copenh) 127:97-99
15. Geller DH, Auchus RJ, Mendonça BB, Miller WL 1997 The genetic and functional basis of isolated 17,20 lyase deficiency. Nat Genet 17:201-205
16. Kitamura M, Buczko E, Dufau ML 1991 Dissociation of hydroxylase and lyase activities by site-directed mutagenesis of the rat P450-17α. Mol Endocrinol 5:1373-1380
17. Lin D, Zhang L, Chiao E, Miller WL 1994 Modeling and mutagenesis of the active site of human P450c17. Mol Endocrinol 8:392-402
18. Auchus RJ, Geller DH, Lee TC, Miller WL 1998 The regulation of human P450c17 activity: Relationship to premature adrenarche and the polycystic ovary syndrome. Trends Endocrinol Metab 9:47-50
19. 5 augments the 17,20 lyase activity of human P450c17 without direct electron transfer. J Biol Chem 273:3158-3165
20. Pompon D, Louerat B, Bronine A, Urban P 1996 Yeast expression of animal and plant P450s in optimized redox environments. Methods Enzymol 272:51-64
21. 21 side-chain cleavage). Biochem Biophys Res Commun 108:454-460
22. Kominami S, Ogawa N, Morimune R, Huang DY, Takemori S 1992 The role of cytochrome b5 in adrenal microsomal steroidogenesis. J Steroid Biochem Mol Biol 42:57-64
23. 5 in the biosynthesis of androgens by human P450c17. Arch Biochem Biophys 317:343-347
24. Fardella CE, Hum DW, Homoki J, Miller WL 1994 Point mutation Arg440 to His in cytochrome P450c17 causes severe 17α-hydroxylase deficiency. J Clin Endocrinol Metab 79:160-164
25. LaFlamme N, Leblanc J-F, Mailloux J, Faure N, Labrie F, Simard J 1996 Mutation R96W in cytochrome P450c17 gene causes combined 17α-hydroxylase/17,20 lyase deficiency in two French Canadian patients. J Clin Endocrinol Metab 81:264-268
26. Biason-Lauber A, Leiberman E, Zachmann M 1997 A single amino acid substitution in the putative redox partner-binding site of P450c17 as cause of isolated 17,20 lyase deficiency. J Clin Endocrinol Metab 82:3807-3812
27. Orentreich N, Brind JL, Rizer RL, Vogelman JH 1984 Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 59:551-555
28. Dunaif A 1995 Hyperandrogenic anovulation (PCOS): A unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am J Med 98 [Suppl 1A]:33S-39S
29. Zhang L, Rodriguez H, Ohno S, Miller WL 1995 Serine phosphorylation of human P450c17 increases 17,20 lyase activity: Implications for adrenarche and for the polycystic ovary syndrome. Proc Natl Acad Sci USA 92:10619-10623
30. Biason-Lauber A, Kempken B, Zachmann M Molecular basis of 17α-hydroxylase/17,20-lyase deficiency as a model to investigate enzyme activity regulation. Program of the 80th Annual Meeting of The Endocrine Society, New Orleans, LA, 1998, p 177 (Abstract)
31. Gietz D, St. Jean A, Woods RA, Schiestl RH 1992 Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res 20:1425
32. Omura T, Sato R 1964 The carbon monoxide-binding pigment of liver microsomes. J Biol Chem 239:2370-2378
33. Auchus RJ, Palmer JO, Carrell HL, Covey DF 1989 Preparation of 14,15 secoestra-1,3,5 (10)-trien-15-ynes, inhibitors of estradiol dehydrogenase. Steroids 53:77-96
34. 106→ Pro causes 17α-hydroxylase deficiency. J Biol Chem 266:15992-15998
35. Yoo M, Steggles AW 1988 The complete nucleotide sequence of human liver cytochrome b5 mRNA. Biochem Biophys Res Commun 156:576-580
36. 5 potentiation of cytochrome P-450 catalytic activity demonstrated by a vaccinia virus-mediated in situ reconstitution system. Proc Natl Acad Sci USA 87:5425-5429