| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| It was found that the formation of androsta 5 , 16 dien 3 beta ol ( 5 , 16 diene ) and androst 5 ene 3 beta , 17 alpha diol ( 17 alpha hydroxyandrogen ) from pregnenolone was catalyzed by both the isoforms and that the two conversions were dependent on the presence of cytochrome b 5 ( cyt b 5 ) . 3 beta Hydroxyandrost 5 ene 17 beta carbaldehyde ( aldehyde ) , an analogue of the physiological substrate pregnenolone , was handled as a substrate by both isoforms of CYP 17 . ^^^ The aldehyde underwent cleavage to produce the 5 , 16 diene plus the 17 alpha hydroxyandrogen , at rates approximately 8 and 3 fold higher than any physiological reaction catalyzed , in the absence of cytochrome b 5 , by the pig and human CYP 17 isoforms , respectively . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Cytochrome b 5 ( cyt b 5 ) can also participate in the regulation of adrenal microsomal steroid hydroxylase activities by changing the rates of the P450c21 and P450c17 reactions or by affecting the 17 alpha hydroxylation : 17 , 20 lyase ratio of progesterone , by P450c17 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| The role of cytochrome b 5 in the biosynthesis of androgens by human P450c17 . ^^^ Human cytochrome b 5 has a profound effect on the 17 , 20 lyase activities catalyzed by purified , human cytochrome P450c17 . ^^^ Other activities catalyzed by P450c17 include 17 alpha hydroxylation of progesterone and pregnenolone and are much less influenced by cytochrome b 5 . ^^^ These studies using purified systems suggest that cytochrome b 5 plays a role in regulating the activities of P450c17 to optimize the balance between sex hormone synthesis and glucocorticoid synthesis . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Cytochrome P450c17 from porcine and bovine adrenal catalyses the formation of 5 , 16 androstadien 3 beta ol from pregnenolone in the presence of cytochrome b 5 . ^^^ Cytochrome P450c17 purified from adult porcine testis and adrenal glands and bovine adrenal glands had only C 17 hydroxylase / lyase activity in the absence of cytochrome b 5 . ^^^ However , when cytochrome b 5 isolated from porcine testis was added , andien beta synthase activity was detected in all three preparations of cytochrome P450c17 , with the highest activity found in the porcine preparations . ^^^ Levels of mRNA for cytochrome b 5 relative to cytochrome P450c17 mRNA were five times higher in porcine testis than in porcine adrenal . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Modulation of the activity of human 17 alpha hydroxylase 17 , 20 lyase ( CYP 17 ) by cytochrome b 5 : endocrinological and mechanistic implications . ^^^ Like the pig CYP 17 , the human CYP 17 also catalysed the cytochrome b 5 dependent direct cleavage of pregnenolone into the delta 5 , 16 steroid , but unlike it the human enzyme did not cleave progesterone at all . 17 alpha Hydroxypregnenolone was , however , cleaved into the corresponding androgen but only in the presence of cytochrome b 5 . 17 alpha Hydroxyprogesterone was a poor substrate for the human CYP 17 ; although it was converted into androstenedione in the presence of cytochrome b 5 its K ( m ) was 5 times higher and Vmax . 2 . 6 times lower than those for the hydroxylation of progesterone . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Interaction of human CYP 17 ( P 450 ( 17alpha ) , 17alpha hydroxylase 17 , 20 lyase ) with cytochrome b 5 : importance of the orientation of the hydrophobic domain of cytochrome b 5 . ^^^ Human CYP 17 ( P 450 ( 17alpha ) , 17alpha hydroxylase 17 , 20 lyase ) catalysed side chain cleavage of 17alpha hydroxyprogestogens into androgens is greatly dependent on the presence of cytochrome b 5 . ^^^ In the present study the abilities of five different forms of cytochrome b 5 to support the side chain cleavage activity of CYP 17 were compared . ^^^ The results highlight that productive interaction between cytochrome b 5 and CYP 17 is governed not only by the presence of a membrane insertable hydrophobic region on the cytochrome b 5 but also by its defined spatial orientation at the C terminal . . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| CYP 17 is partly denatured to P 420 during hCG action , but other heme proteins ( cytochrome b 5 ) remain unchanged . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Cytochrome b 5 augments the 17 , 20 lyase activity of human P450c17 without direct electron transfer . ^^^ Cytochrome b 5 augments the 17 , 20 lyase activity of cytochrome P450c17 in vitro , but this has not been demonstrated in membranes , and the mechanism of this action is unknown . ^^^ We expressed human P450c17 , human P 450 oxidoreductase ( OR ) , and / or human cytochrome b 5 in Saccharomyces cerevisiae and analyzed the 17alpha hydroxylase and 17 , 20 lyase activities of the resulting yeast microsomes . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Cytochrome b 5 , a component of the electron transfer system increases the relative activity of 17 , 20 lyase to 17alpha hydroxylase of P450c17 in vitro . ^^^ All of the adenomas were composed mainly of compact cells , which exhibited immunoreactive staining for cytochrome b 5 as well as for P450c17 and 3beta hydroxysteroid dehydrogenase ( 3beta HSD ) . ^^^ These results immunohistochemically support the functional association of b 5 with androgen production through interaction with P450c17 and the previous finding that higher concentrations of cytochrome b 5 are associated with greater production of adrenal androgens in adrenocortical adenomas from patients with Cushing ' s syndrome . . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| The studies of enzymatic regulation of P450c17 suggest that cytochrome b 5 ( b 5 ) , a heme protein , may switch the reaction of P450c17 by enhancing the 17 , 20 lyase activity to increase the level of plasma C 19 steroids . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| This site , through which P450c17 interacts with P 450 oxidoreductase to receive the electrons needed for catalysis , can be allosterically influenced by cytochrome b 5 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| P450c17 mutations R347H and R358Q selectively disrupt 17 , 20 lyase activity by disrupting interactions with P 450 oxidoreductase and cytochrome b 5 . ^^^ We have recently shown that cytochrome b 5 facilitates 17 , 20 lyase activity by allosterically promoting the interaction of P450c17 with P 450 oxidoreductase ( OR ) and that the human P450c17 mutations , R347H and R358Q , selectively destroy 17 , 20 lyase activity while sparing 17alpha hydroxylase activity . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Cytochrome b 5 , a microsomal electron transfer protein , enhances lyase activities of rat and human P450c17 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Interestingly , cytochrome b 5 was found to dramatically inhibit both P 450 reductase and Fpr Fld supported P450c17 progesterone 17alpha hydroxylase activity while in contrast 17alpha OH pregnenolone lyase activity was stimulated by b 5 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Control of androgen biosynthesis in the human through the interaction of Arg 347 and Arg 358 of CYP 17 with cytochrome b 5 . ^^^ The lyase activity of human CYP 17 ( 17alpha hydroxylase 17 , 20 lyase also P 450c17 or P 45017alpha ) is greatly dependent on the presence of cytochrome b 5 , and this effect has been ascribed an important regulatory role [ Lee Robichaud , Wright , Akhtar and Akhtar ( 1995 ) Biochem . ^^^ These residues are invoked to mediate protein protein interaction between cytochrome b 5 and CYP 17 , which ' awakens ' the lyase activity of the enzyme required for androgen formation . . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Role of cytochrome b 5 in the 17 , 20 lyase activity of P450c17 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Immunohistochemistry for P 450 side chain cleavage ( P450scc ) , 17alpha hydroxylase ( P450c17 ) , dehydroepiandrosterone sulfotransferase ( DHEA ST ) , P 450 oxidoreductase , cytochrome b 5 , and 3beta hydroxysteroid dehydrogenase ( 3betaHSD ) was per formed in these specimens , and the immuno intensity was evaluated using CAS 200 computed image analysis system . ^^^ Immunoreactivity of P 450 oxidoreductase and cytochrome b 5 , components of the electron transfer system hypothesized to regulate the 17 20 lyase activity of P450c17 , was weak in all three zones of adrenal cortex from 7 months to 5 years , and became more marked in the zona reticularis after age 5 years . 3betaHSD immunoreactivity was marked in all three zones of the adrenal cortex from 7 months to 8 years but thereafter decreased in the zona reticularis . ^^^ The increased level of P450c17 , DHEA ST , P 450 oxidoreductase , and cytochrome b 5 , and the decreased level of 3betaHSD in the reticularis is likely to contribute to increased C 19 steroid production during adrenarche . . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| This system has been shown in vitro to involve both cytochrome P450c17 and cytochrome b 5 . ^^^ Western blots were used to determine the amounts of cytochrome b 5 and cytochrome P450c17 protein in testis , and two immunoreactive cytochrome b 5 proteins of approximately 12 and 16 kDa were found . ^^^ Levels of cytochrome P450c17 or the high molecular weight cytochrome b 5 in testis were not significantly correlated to levels of 16 androstene steroids in fat . ^^^ These results indicate that increased levels of a low molecular weight immunoreactive cytochrome b 5 protein , and not of cytochrome P450c17 , are related to increased testicular 16 androstene steroid production and accumulation in fat . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Lysine mutagenesis identifies cationic charges of human CYP 17 that interact with cytochrome b 5 to promote male sex hormone biosynthesis . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| The primate adrenal zona reticularis is defined by expression of cytochrome b 5 , 17alpha hydroxylase / 17 , 20 lyase cytochrome P 450 ( P450c17 ) and NADPH cytochrome P 450 reductase ( reductase ) but not 3beta hydroxysteroid dehydrogenase / delta5 4 isomerase ( 3beta HSD ) . ^^^ Biochemical studies suggest that 17 , 20 lyase activity , and thus efficient synthesis of androgens by human P450c17 , requires both reductase and the accessory protein cytochrome b 5 . ^^^ These data provide essential evidence in support of a functional role for cytochrome b 5 in the regional control of 17alpha hydroxylase and 17 , 20 lyase activities of P450c17 and thereby adrenal C 19 steroid secretion by the primate adrenal gland . . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| P450c17 appears to catalyze 17 , 20 lyase activity only if P450c17 has undergone serine phosphorylation and has access to cytochrome b 5 as an allosteric cofactor . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| In this study , we examined the immunolocalization of steroidogenic enzymes and their local regulation , including adrenal 4 binding protein ( Ad4BP or NR5A1 ) , steroidogenic acute regulatory protein ( StAR ) , P 450 cholesterol side chain cleavage ( P450scc or CYP11A1 ) , P 450 17alpha hydroxylase / 17 , 20 lyase ( P450c17 or CYP 17 ) , 3beta hydroxysteroid dehydrogenase / isomerase ( 3beta HSD ) , P 450 21 hydroxylase ( P450c21 or CYP 21 ) , dehydroepiandrosterone sulfotransferase ( DHEA ST ) , P 450 oxidoreductase and cytochrome b 5 , in the human fetal adrenal gland ( n=31 ) obtained from fetuses ranging in ages from 14 to 40 weeks of gestation . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Assessment of the ability of type 2 cytochrome b 5 to modulate 17 , 20 lyase activity of human P450c17 . ^^^ It has been previously shown that cytochrome b 5 ( cyt b 5 ) could facilitate the 17 , 20 lyase activity of human P450c17 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| The developmental expressions of cytochrome b 5 ( b 5 ) , 17 alpha hydroxylase / 17 , 20 lyase cytochrome P 450 ( P450c17 ) , and 3 beta hydroxysteroid dehydrogenase were examined in primate fetal adrenals by immunocytochemistry from 50 160 d gestation . ^^^ However , the lack of cytochrome b 5 and P450c17 expression in the FZ of the developing macaque adrenal cortex for much of the second and third trimesters distinguishes it from the mature zona reticularis seen in adult animals . . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Recent detailed studies of the biochemical properties of the mutant CYP 17 enzymes from patients with isolated 17 , 20 lyase deficiency demonstrate that alterations in the interaction of CYP 17 with its redox partner proteins P 450 oxidoreductase and cytochrome b 5 form the biochemical basis for these selective enzyme defects . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| We transfected human embryonic kidney ( HEK 293 ) cells with various amounts of vectors expressing P450c17 , NADPH cytochrome P 450 reductase , and cytochrome b 5 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Expression of proteins responsible for these activities , aromatase ( P450arom ) and 17 alpha hydroxylase / 17 , 20 lyase ( P450c17 ) cytochromes P 450 , reductase , and for the first time in ovarian tissues cytochrome b 5 , were examined by Western immunoblot and immunocytochemistry . ^^^ Reductase expression did not change with stage of follicular development , but cytochrome b 5 , P450c17 , and P450arom were markedly lower in post LH tissues . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Colocalization of P450c17 and cytochrome b 5 in androgen synthesizing tissues of the human . ^^^ Androgen synthesis by these steroidogenic tissues requires the bifunctional enzyme cytochrome P450c17 , which catalyzes both 17 hydroxylase and 17 , 20 lyase activities . 17 , 20 lyase activity is relevant to the regulation of androgen production , and is allosterically modulated through the action of an accessory protein , cytochrome b 5 ( CytB 5 ) . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| The cationic charges on Arg 347 , Arg 358 and Arg 449 of human cytochrome P450c17 ( CYP 17 ) are essential for the enzyme ' s cytochrome b 5 dependent acyl carbon cleavage activities . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| These conversions require pairs of electron transfer proteins or redox partners , which are adrenodoxin and adrenodoxin reductase for CYP11A1 and cytochrome P 450 oxidoreductase and cytochrome b 5 for CYP 17 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Xenopus laevis CYP 17 regulates androgen biosynthesis independent of the cofactor cytochrome b 5 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Ontogeny of cytochrome B 5 and cytochrome P 450 C17 in the human fetal adrenal gland during normal development . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Regulation of 17 , 20 lyase activity by cytochrome b 5 and by serine phosphorylation of P450c17 . ^^^ We have shown that serine phosphorylation of P450c17 and the allosteric action of cytochrome b 5 increase 17 , 20 lyase activity , but it has not been apparent whether these two post translational mechanisms interact . ^^^ Using purified enzyme systems , we now show that the actions of cytochrome b 5 are independent of the state of P450c17 phosphorylation . ^^^ When expressed in bacteria , human P450c17 required either cytochrome b 5 or phosphorylation for 17 , 20 lyase activity . ^^^ Cytochrome b 5 and phosphorylation enhance 17 , 20 lyase activity independently of each other , probably by increasing the interaction between P450c17 and NADPH cytochrome P 450 oxidoreductase . . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Sex steroid synthesis requires the 17 , 20 lyase activity of P450c17 , which is enhanced by cytochrome b 5 , acting as an allosteric factor to promote association of P450c17 with its electron donor , P 450 oxidoreductase . ^^^ Transcription of cytochrome b 5 shares many features with the regulation of P450c17 , whose activity it enhances . . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| This ratio is regulated posttranslationally by at least three factors : the abundance of the electron donating protein P 450 oxidoreductase ( POR ) , the presence of cytochrome b 5 and the serine phosphorylation of P450c17 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Real time RT PCR was performed for LH / HCG receptor ( LHCGR ) , steroidogenic acute regulatory ( StAR ) , cholesterol side chain cleavage ( CYP11A ) , 3beta hydroxysteroid dehydrogenase type 1 ( HSD3B1 ) and type 2 ( HSD3B2 , 3betaHSD ) , 17a hydroxylase ( CYP 17 ) , cytochrome b 5 ( CytB 5 ) , and aromatase ( CYP 19 ) . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| Human cytochrome b 5 requires residues E 48 and E 49 to stimulate the 17 , 20 lyase activity of cytochrome P450c17 . ^^^ |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00167 and P05093 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Cytochrome b 5 ( cyt b 5 ) can also participate in the regulation of adrenal microsomal steroid hydroxylase activities by changing the rates of the P450c21 and P450c17 reactions or by affecting the 17 alpha hydroxylation : 17 , 20 lyase ratio of progesterone , by P450c17 . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| The role of cytochrome b 5 in the biosynthesis of androgens by human P450c17 . ^^^ Human cytochrome b 5 has a profound effect on the 17 , 20 lyase activities catalyzed by purified , human cytochrome P450c17 . ^^^ Other activities catalyzed by P450c17 include 17 alpha hydroxylation of progesterone and pregnenolone and are much less influenced by cytochrome b 5 . ^^^ These studies using purified systems suggest that cytochrome b 5 plays a role in regulating the activities of P450c17 to optimize the balance between sex hormone synthesis and glucocorticoid synthesis . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Interestingly , cytochrome b 5 was found to dramatically inhibit both P 450 reductase and Fpr Fld supported P450c17 progesterone 17alpha hydroxylase activity while in contrast 17alpha OH pregnenolone lyase activity was stimulated by b 5 . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Cytochrome b 5 , a component of the electron transfer system increases the relative activity of 17 , 20 lyase to 17alpha hydroxylase of P450c17 in vitro . ^^^ All of the adenomas were composed mainly of compact cells , which exhibited immunoreactive staining for cytochrome b 5 as well as for P450c17 and 3beta hydroxysteroid dehydrogenase ( 3beta HSD ) . ^^^ These results immunohistochemically support the functional association of b 5 with androgen production through interaction with P450c17 and the previous finding that higher concentrations of cytochrome b 5 are associated with greater production of adrenal androgens in adrenocortical adenomas from patients with Cushing ' s syndrome . . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| The studies of enzymatic regulation of P450c17 suggest that cytochrome b 5 ( b 5 ) , a heme protein , may switch the reaction of P450c17 by enhancing the 17 , 20 lyase activity to increase the level of plasma C 19 steroids . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| This site , through which P450c17 interacts with P 450 oxidoreductase to receive the electrons needed for catalysis , can be allosterically influenced by cytochrome b 5 . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| P450c17 mutations R347H and R358Q selectively disrupt 17 , 20 lyase activity by disrupting interactions with P 450 oxidoreductase and cytochrome b 5 . ^^^ We have recently shown that cytochrome b 5 facilitates 17 , 20 lyase activity by allosterically promoting the interaction of P450c17 with P 450 oxidoreductase ( OR ) and that the human P450c17 mutations , R347H and R358Q , selectively destroy 17 , 20 lyase activity while sparing 17alpha hydroxylase activity . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Cytochrome P450c17 from porcine and bovine adrenal catalyses the formation of 5 , 16 androstadien 3 beta ol from pregnenolone in the presence of cytochrome b 5 . ^^^ Cytochrome P450c17 purified from adult porcine testis and adrenal glands and bovine adrenal glands had only C 17 hydroxylase / lyase activity in the absence of cytochrome b 5 . ^^^ However , when cytochrome b 5 isolated from porcine testis was added , andien beta synthase activity was detected in all three preparations of cytochrome P450c17 , with the highest activity found in the porcine preparations . ^^^ Levels of mRNA for cytochrome b 5 relative to cytochrome P450c17 mRNA were five times higher in porcine testis than in porcine adrenal . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Cytochrome b 5 augments the 17 , 20 lyase activity of human P450c17 without direct electron transfer . ^^^ Cytochrome b 5 augments the 17 , 20 lyase activity of cytochrome P450c17 in vitro , but this has not been demonstrated in membranes , and the mechanism of this action is unknown . ^^^ We expressed human P450c17 , human P 450 oxidoreductase ( OR ) , and / or human cytochrome b 5 in Saccharomyces cerevisiae and analyzed the 17alpha hydroxylase and 17 , 20 lyase activities of the resulting yeast microsomes . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| This system has been shown in vitro to involve both cytochrome P450c17 and cytochrome b 5 . ^^^ Western blots were used to determine the amounts of cytochrome b 5 and cytochrome P450c17 protein in testis , and two immunoreactive cytochrome b 5 proteins of approximately 12 and 16 kDa were found . ^^^ Levels of cytochrome P450c17 or the high molecular weight cytochrome b 5 in testis were not significantly correlated to levels of 16 androstene steroids in fat . ^^^ These results indicate that increased levels of a low molecular weight immunoreactive cytochrome b 5 protein , and not of cytochrome P450c17 , are related to increased testicular 16 androstene steroid production and accumulation in fat . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| The primate adrenal zona reticularis is defined by expression of cytochrome b 5 , 17alpha hydroxylase / 17 , 20 lyase cytochrome P 450 ( P450c17 ) and NADPH cytochrome P 450 reductase ( reductase ) but not 3beta hydroxysteroid dehydrogenase / delta5 4 isomerase ( 3beta HSD ) . ^^^ Biochemical studies suggest that 17 , 20 lyase activity , and thus efficient synthesis of androgens by human P450c17 , requires both reductase and the accessory protein cytochrome b 5 . ^^^ These data provide essential evidence in support of a functional role for cytochrome b 5 in the regional control of 17alpha hydroxylase and 17 , 20 lyase activities of P450c17 and thereby adrenal C 19 steroid secretion by the primate adrenal gland . . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| P450c17 appears to catalyze 17 , 20 lyase activity only if P450c17 has undergone serine phosphorylation and has access to cytochrome b 5 as an allosteric cofactor . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Role of cytochrome b 5 in the 17 , 20 lyase activity of P450c17 . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Immunohistochemistry for P 450 side chain cleavage ( P450scc ) , 17alpha hydroxylase ( P450c17 ) , dehydroepiandrosterone sulfotransferase ( DHEA ST ) , P 450 oxidoreductase , cytochrome b 5 , and 3beta hydroxysteroid dehydrogenase ( 3betaHSD ) was per formed in these specimens , and the immuno intensity was evaluated using CAS 200 computed image analysis system . ^^^ Immunoreactivity of P 450 oxidoreductase and cytochrome b 5 , components of the electron transfer system hypothesized to regulate the 17 20 lyase activity of P450c17 , was weak in all three zones of adrenal cortex from 7 months to 5 years , and became more marked in the zona reticularis after age 5 years . 3betaHSD immunoreactivity was marked in all three zones of the adrenal cortex from 7 months to 8 years but thereafter decreased in the zona reticularis . ^^^ The increased level of P450c17 , DHEA ST , P 450 oxidoreductase , and cytochrome b 5 , and the decreased level of 3betaHSD in the reticularis is likely to contribute to increased C 19 steroid production during adrenarche . . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Cytochrome b 5 , a microsomal electron transfer protein , enhances lyase activities of rat and human P450c17 . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| In this study , we examined the immunolocalization of steroidogenic enzymes and their local regulation , including adrenal 4 binding protein ( Ad4BP or NR5A1 ) , steroidogenic acute regulatory protein ( StAR ) , P 450 cholesterol side chain cleavage ( P450scc or CYP11A1 ) , P 450 17alpha hydroxylase / 17 , 20 lyase ( P450c17 or CYP 17 ) , 3beta hydroxysteroid dehydrogenase / isomerase ( 3beta HSD ) , P 450 21 hydroxylase ( P450c21 or CYP 21 ) , dehydroepiandrosterone sulfotransferase ( DHEA ST ) , P 450 oxidoreductase and cytochrome b 5 , in the human fetal adrenal gland ( n=31 ) obtained from fetuses ranging in ages from 14 to 40 weeks of gestation . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Assessment of the ability of type 2 cytochrome b 5 to modulate 17 , 20 lyase activity of human P450c17 . ^^^ It has been previously shown that cytochrome b 5 ( cyt b 5 ) could facilitate the 17 , 20 lyase activity of human P450c17 . ^^^ |
|
| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| The developmental expressions of cytochrome b 5 ( b 5 ) , 17 alpha hydroxylase / 17 , 20 lyase cytochrome P 450 ( P450c17 ) , and 3 beta hydroxysteroid dehydrogenase were examined in primate fetal adrenals by immunocytochemistry from 50 160 d gestation . ^^^ However , the lack of cytochrome b 5 and P450c17 expression in the FZ of the developing macaque adrenal cortex for much of the second and third trimesters distinguishes it from the mature zona reticularis seen in adult animals . . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| We transfected human embryonic kidney ( HEK 293 ) cells with various amounts of vectors expressing P450c17 , NADPH cytochrome P 450 reductase , and cytochrome b 5 . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Expression of proteins responsible for these activities , aromatase ( P450arom ) and 17 alpha hydroxylase / 17 , 20 lyase ( P450c17 ) cytochromes P 450 , reductase , and for the first time in ovarian tissues cytochrome b 5 , were examined by Western immunoblot and immunocytochemistry . ^^^ Reductase expression did not change with stage of follicular development , but cytochrome b 5 , P450c17 , and P450arom were markedly lower in post LH tissues . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Colocalization of P450c17 and cytochrome b 5 in androgen synthesizing tissues of the human . ^^^ Androgen synthesis by these steroidogenic tissues requires the bifunctional enzyme cytochrome P450c17 , which catalyzes both 17 hydroxylase and 17 , 20 lyase activities . 17 , 20 lyase activity is relevant to the regulation of androgen production , and is allosterically modulated through the action of an accessory protein , cytochrome b 5 ( CytB 5 ) . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| The cationic charges on Arg 347 , Arg 358 and Arg 449 of human cytochrome P450c17 ( CYP 17 ) are essential for the enzyme ' s cytochrome b 5 dependent acyl carbon cleavage activities . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Ontogeny of cytochrome B 5 and cytochrome P 450 C17 in the human fetal adrenal gland during normal development . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Regulation of 17 , 20 lyase activity by cytochrome b 5 and by serine phosphorylation of P450c17 . ^^^ We have shown that serine phosphorylation of P450c17 and the allosteric action of cytochrome b 5 increase 17 , 20 lyase activity , but it has not been apparent whether these two post translational mechanisms interact . ^^^ Using purified enzyme systems , we now show that the actions of cytochrome b 5 are independent of the state of P450c17 phosphorylation . ^^^ When expressed in bacteria , human P450c17 required either cytochrome b 5 or phosphorylation for 17 , 20 lyase activity . ^^^ Cytochrome b 5 and phosphorylation enhance 17 , 20 lyase activity independently of each other , probably by increasing the interaction between P450c17 and NADPH cytochrome P 450 oxidoreductase . . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Sex steroid synthesis requires the 17 , 20 lyase activity of P450c17 , which is enhanced by cytochrome b 5 , acting as an allosteric factor to promote association of P450c17 with its electron donor , P 450 oxidoreductase . ^^^ Transcription of cytochrome b 5 shares many features with the regulation of P450c17 , whose activity it enhances . . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| This ratio is regulated posttranslationally by at least three factors : the abundance of the electron donating protein P 450 oxidoreductase ( POR ) , the presence of cytochrome b 5 and the serine phosphorylation of P450c17 . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Human cytochrome b 5 requires residues E 48 and E 49 to stimulate the 17 , 20 lyase activity of cytochrome P450c17 . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| It was found that the formation of androsta 5 , 16 dien 3 beta ol ( 5 , 16 diene ) and androst 5 ene 3 beta , 17 alpha diol ( 17 alpha hydroxyandrogen ) from pregnenolone was catalyzed by both the isoforms and that the two conversions were dependent on the presence of cytochrome b 5 ( cyt b 5 ) . 3 beta Hydroxyandrost 5 ene 17 beta carbaldehyde ( aldehyde ) , an analogue of the physiological substrate pregnenolone , was handled as a substrate by both isoforms of CYP 17 . ^^^ The aldehyde underwent cleavage to produce the 5 , 16 diene plus the 17 alpha hydroxyandrogen , at rates approximately 8 and 3 fold higher than any physiological reaction catalyzed , in the absence of cytochrome b 5 , by the pig and human CYP 17 isoforms , respectively . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Modulation of the activity of human 17 alpha hydroxylase 17 , 20 lyase ( CYP 17 ) by cytochrome b 5 : endocrinological and mechanistic implications . ^^^ Like the pig CYP 17 , the human CYP 17 also catalysed the cytochrome b 5 dependent direct cleavage of pregnenolone into the delta 5 , 16 steroid , but unlike it the human enzyme did not cleave progesterone at all . 17 alpha Hydroxypregnenolone was , however , cleaved into the corresponding androgen but only in the presence of cytochrome b 5 . 17 alpha Hydroxyprogesterone was a poor substrate for the human CYP 17 ; although it was converted into androstenedione in the presence of cytochrome b 5 its K ( m ) was 5 times higher and Vmax . 2 . 6 times lower than those for the hydroxylation of progesterone . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Real time RT PCR was performed for LH / HCG receptor ( LHCGR ) , steroidogenic acute regulatory ( StAR ) , cholesterol side chain cleavage ( CYP11A ) , 3beta hydroxysteroid dehydrogenase type 1 ( HSD3B1 ) and type 2 ( HSD3B2 , 3betaHSD ) , 17a hydroxylase ( CYP 17 ) , cytochrome b 5 ( CytB 5 ) , and aromatase ( CYP 19 ) . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Interaction of human CYP 17 ( P 450 ( 17alpha ) , 17alpha hydroxylase 17 , 20 lyase ) with cytochrome b 5 : importance of the orientation of the hydrophobic domain of cytochrome b 5 . ^^^ Human CYP 17 ( P 450 ( 17alpha ) , 17alpha hydroxylase 17 , 20 lyase ) catalysed side chain cleavage of 17alpha hydroxyprogestogens into androgens is greatly dependent on the presence of cytochrome b 5 . ^^^ In the present study the abilities of five different forms of cytochrome b 5 to support the side chain cleavage activity of CYP 17 were compared . ^^^ The results highlight that productive interaction between cytochrome b 5 and CYP 17 is governed not only by the presence of a membrane insertable hydrophobic region on the cytochrome b 5 but also by its defined spatial orientation at the C terminal . . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| CYP 17 is partly denatured to P 420 during hCG action , but other heme proteins ( cytochrome b 5 ) remain unchanged . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Control of androgen biosynthesis in the human through the interaction of Arg 347 and Arg 358 of CYP 17 with cytochrome b 5 . ^^^ The lyase activity of human CYP 17 ( 17alpha hydroxylase 17 , 20 lyase also P 450c17 or P 45017alpha ) is greatly dependent on the presence of cytochrome b 5 , and this effect has been ascribed an important regulatory role [ Lee Robichaud , Wright , Akhtar and Akhtar ( 1995 ) Biochem . ^^^ These residues are invoked to mediate protein protein interaction between cytochrome b 5 and CYP 17 , which ' awakens ' the lyase activity of the enzyme required for androgen formation . . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Lysine mutagenesis identifies cationic charges of human CYP 17 that interact with cytochrome b 5 to promote male sex hormone biosynthesis . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Recent detailed studies of the biochemical properties of the mutant CYP 17 enzymes from patients with isolated 17 , 20 lyase deficiency demonstrate that alterations in the interaction of CYP 17 with its redox partner proteins P 450 oxidoreductase and cytochrome b 5 form the biochemical basis for these selective enzyme defects . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| These conversions require pairs of electron transfer proteins or redox partners , which are adrenodoxin and adrenodoxin reductase for CYP11A1 and cytochrome P 450 oxidoreductase and cytochrome b 5 for CYP 17 . ^^^ |
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| Interacting proteins: P05093 and P00167 |
Pubmed |
SVM Score :0.0 |
| Xenopus laevis CYP 17 regulates androgen biosynthesis independent of the cofactor cytochrome b 5 . ^^^ |
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