ライフサイエンスコーパス: 17,20-lyase

1 ha-hydroxylase, 8.4 +/- 0.6 microm; K(I) for 17,20-lyase, 5.3 +/- 0.7 microm).

2 ms have high 17alpha-hydroxylase relative to 17,20-lyase activities and preferentially mediate one of

3 questioned because 17 alpha-hydroxylase and 17,20-lyase activities are catalyzed by a single enzyme,

4 (3betaHSDII) and the 17alpha-hydroxylase and 17,20-lyase activities of cytochrome P450c17.

5 iae and analyzed the 17alpha-hydroxylase and 17,20-lyase activities of the resulting yeast microsomes

6 We found that the 17,20-lyase activities of Xenopus CYP17 exceeded the 17a

7 y P450c17 have 17alpha-hydroxylase and trace 17,20-lyase activities toward both Delta4 and Delta5 ste

8 ly inhibited CYP17A1 17alpha-hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar

9 hich catalyzes both 17 alpha-hydroxylase and 17,20-lyase activities.

10 synthesis, has both 17 alpha-hydroxylase and 17,20-lyase activities.

11 ajor glucocorticoid in many animals, and the 17, 20-lyase activity required for the production of and

12 ily with the P450c17.OR complex to stimulate 17, 20-lyase activity.

13 on 17alpha-hydroxylase activity but reduced 17,20 lyase activity by 30%.

14 Inhibition of 17,20 lyase activity by PP2A was concentration-dependent

15 PP2A but not PP4 inhibited 17,20 lyase activity in microsomes from cultured cells,

16 pha, but not knockdown of p38beta, inhibited 17,20 lyase activity in NCI-H295A cells.

17 Cytochrome b5 and phosphorylation enhance 17,20 lyase activity independently of each other, probab

18 Whether or not P450c17 catalyzes 17,20 lyase activity is determined by three post-transla

19 nthesis, which may or may not be followed by 17,20 lyase activity needed for sex steroid synthesis.

20 roxylation needed for cortisol synthesis and 17,20 lyase activity needed to produce sex steroids.

21 17alpha-hydroxylase activity of P450c17, and 17,20 lyase activity of P450c17.

22 ed that p38alpha, but not p38beta, conferred 17,20 lyase activity on P450c17.

23 equired for glucocorticoid synthesis and the 17,20 lyase activity required for sex steroid synthesis.

24 allosteric action of cytochrome b5 increase 17,20 lyase activity, but it has not been apparent wheth

25 horylation of P450c17 specifically increases 17,20 lyase activity, but the physiological factors regu

26 P450c17 in a fashion that confers increased 17,20 lyase activity, implying that the production of ad

27 acid, fostriecin, and cantharidin increased 17,20 lyase activity, suggesting involvement of protein

28 t a non-canonical site, conferring increased 17,20 lyase activity.

29 either cytochrome b5 or phosphorylation for 17,20 lyase activity.

30 ls inhibited PP2A, but not PP4, and fostered 17,20 lyase activity.

31 n of PP2A by small interfering RNA increased 17,20 lyase activity.

32 vity between E6 and E7 and the presence of C(17,20)-lyase activity at E7.

33 en these two proteins, which is critical for 17,20-lyase activity and androgen biosynthesis.

34 re missense mutations cause isolated loss of 17,20-lyase activity by disrupting interactions of redox

35 on E48G + E49G did not impair stimulation of 17,20-lyase activity by wild-type b5, suggesting that th

36 lude that mutation E305G selectively impairs 17,20-lyase activity for DHEA synthesis despite an incre

37 However, mutation E305G lacks 17,20-lyase activity for the conversion of 17alpha-hydro

38 es E48 and E49 are required to stimulate the 17,20-lyase activity of CYP17A1, but these same residues

39 n retained the full ability to stimulate the 17,20-lyase activity of CYP17A1.

40 me b5 (b5) are essential for stimulating the 17,20-lyase activity of cytochrome P450c17 (CYP17A1).

41 Cytochrome b5 augments the 17,20-lyase activity of cytochrome P450c17 in vitro, but

42 id not alter the capacity of b5 to stimulate 17,20-lyase activity or appeared to modestly alter the a

43 dies with apo-b5 suggest that stimulation of 17,20-lyase activity results from an allosteric action o

44 -hydroxylation of 21-carbon steroids and the 17,20-lyase activity that cleaves the C17-C20 bond to pr

45 rosterone and androstenedione, respectively (17,20-lyase activity).

46 G lost over 95% of the capacity to stimulate 17,20-lyase activity, yet this mutation retained normal

47 residues abrogated all capacity to stimulate 17,20-lyase activity.

48 tions and assayed their ability to stimulate 17,20-lyase activity.

49 nd possibly R52, mediates the stimulation of 17,20-lyase activity.

50 9, or R52 reduced the maximal stimulation of 17,20-lyase activity.

51 dentify b5 residues critical for stimulating 17,20-lyase activity.

52 eported ability of b5 to selectively enhance 17,20-lyase activity.

53 both necessary and sufficient for microsomal 17,20-lyase activity.

54 sterone, whose biosynthesis requires steroid 17,20-lyase activity.

55 7 alpha-hydroxylase activity but had minimal 17,20-lyase activity.

56 genase, and less often, 17 alpha-hydroxylase/17, 20-lyase and cholesterol desmolase.

57 ydroxylases CYP17A1 (P450c17, 17-hydroxylase/17,20-lyase) and CYP21A2 (P450c21, 21-hydroxylase) catal

58 dazole drugs SB202190 and SB203580 inhibited 17,20 lyase but not 17alpha-hydroxylase activity in huma

59 beta-hydroxylase) and CYP17 (17alpha-hydroxy/17,20-lyase), compound 22 was found to be the best and m

60 amined the expression of 17alpha-hydroxylase/17,20 lyase (CYP17), the enzyme that synthesizes the and

61 d specific inhibitors of 17alpha-hydroxylase/17,20-lyase (CYP17), the key enzyme which catalyzes the

62 of human cytochrome P450 17alpha-hydroxylase-17,20-lyase (CYP17).

63 Abiraterone, a steroidal 17alpha-hydroxylase/17,20-lyase (CYP17A1) inhibitor, blocks this synthetic p

64 Microsomal 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17) catalyzes both the

65 because the index case of apparent isolated 17,20-lyase deficiency had combined deficiencies of both

66 Patients with putative isolated 17,20-lyase deficiency have been reported.

67 These are the first proven cases of isolated 17,20-lyase deficiency, and they demonstrate a novel mec

68 in CYP17 cause combined 17alpha-hydroxylase/17,20-lyase deficiency, but rare missense mutations caus

69 The existence of true isolated 17,20-lyase deficiency, however, has been questioned bec

70 linical and biochemical features of isolated 17,20-lyase deficiency, including micropenis, hypospadia

71 and hormonal findings suggestive of isolated 17,20-lyase deficiency.

72 eactions involving 17alpha-hydroxylase and C(17,20)-lyase in the androgen biosynthesis pathway.

73 tional, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a valida

74 , and reported survival advantage for a CYP (17,20) lyase inhibitor in castration-resistant prostate

75 ational, nonsteroidal, reversible, selective 17,20-lyase inhibitor.

76 terone acetate, a CYP17 (17alpha-hydroxylase/17, 20 lyase) inhibitor, received US FDA approval for us

77 lectron donors to bovine 17alpha-hydroxylase/17,20-lyase P450 (P450c17).

78 h bovine cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450c17) and donates electrons to this enzy

79 city, but not the Michaelis constant, of the 17,20 lyase reaction.

80 ytochrome b5 (b5) stimulates the rate of the 17,20-lyase reaction 10-fold with little influence on 17

81 ding site, so that electron transfer for the 17,20-lyase reaction is selectively lost or diverted to

82 ird, substrate specificity of the subsequent 17,20-lyase reaction may be explained by variation in su

83 regnenolone C17 hydroxylation, followed by a 17,20-lyase reaction to produce dehydroepiandrosterone,

84 17 and OR, further increases the Vmax of the 17,20-lyase reaction without altering 17alpha-hydroxylas

85 rely on the cofactor cytochrome b(5) for the 17,20-lyase reaction, suggesting that the high lyase act

86 estosterone and horse CYP17A to catalyze the 17,20-lyase reaction.

87 the Vmax of both the 17alpha-hydroxylase and 17,20-lyase reactions 5-fold; coexpression of human b5 w

88 with P450c17 also increases the Vmax of the 17,20-lyase reactions but not of the 17alpha-hydroxylase

89 ) catalyzes both the 17alpha-hydroxylase and 17,20-lyase reactions in human steroid biosynthesis.

90 Xenopus CYP17 mediated both 17,20-lyase reactions in the absence of b(5), confirming

91 es and preferentially mediate one of the two 17,20-lyase reactions.

92 vely, via sequential 17alpha-hydroxylase and 17,20-lyase reactions.

93 17alpha-hydroxylase activity, and support of 17,20 lyase using human P450c17.