High impact information on CYP11B1

• Accumulation of adrenodoxin mRNA occurs in cultured bovine adrenocortical cells after treatment with ACTH or dibutyryl-cAMP, similar to that observed for the mitochondrial steroid hydroxylases that it services--namely, the cholesterol side-chain-cleavage cytochrome P-450 and the steroid 11 beta-hydroxylase cytochrome P-450 [1].
• The rate constants observed differ by a factor of up to 10 among the respective adrenodoxin mutants for CYP11A1 but not for CYP11B1 [2].
• The Ad4 site also exists in the promoter regions of other steroidogenic P-450 genes as well as in CYP11B1 [3].
• Especially in the case of CYP11B1 (steroid 11beta-hydroxylase), selectivity is a crucial issue, since sequence homology between this enzyme and the target enzyme is very high (93%) [4].
• The expression of CYP11B1 gene was regulated by cyclic AMP (cAMP)-dependent signaling, whereas that of CYP11B2 gene by calcium ion-signaling as well as cAMP-signaling [5].

Biological context of CYP11B1

• Joint analysis of the influence of CYP11B1 and DGAT1 genetic variation on milk production, somatic cell score, conformation, reproduction, and productive lifespan in German Holstein cattle [6].
• The kinetics of protein-protein interaction and heme reduction between adrenodoxin wild type as well as eight mutants and the cytochromes P450 CYP11A1 and CYP11B1 was studied in detail [2].
• Here, the influence of the electron transport efficiency from adrenodoxin (Adx) to CYP11B1 on the activities of bovine CYP11B1 has been investigated using a liposomal reconstitution system with truncated mutants of Adx [7].
• A full length ovine steroid 11 beta-hydroxylase (cytochrome P-450(11 beta)) cDNA clone from a sheep adrenal cortex cDNA library was isolated [8].

Anatomical context of CYP11B1

• Immunochemical characterization of steroid hydroxylases of adrenocortical mitochondria. 1. Antibodies as inhibitors of cytochrome P450scc (CYP11A1) and P450(11 beta) (CYP11B1) activities [9].
• Interaction of CYP11B1 (cytochrome P-45011 beta) with CYP11A1 (cytochrome P-450scc) in COS-1 cells [10].
• 3. In contrast, the gene encoding CYP11B1 (i.e. the major (non-aldosterone-producing) type of the enzyme) is expressed mainly in the zona fasciculata and its expression depends on physiological concentrations of ACTH [11].

Associations of CYP11B1 with chemical compounds

• The results suggest that the C-terminal peptide of adrenodoxin, especially proline 108, affects the structural integrity of the iron-sulfur cluster and that electron donation from adrenodoxin to CYP11A1 and CYP11B1 is determined at least in part by different features of the cytochromes [12].
• It is able to transfer electrons to horse heart cytochrome c and to bovine cytochromes P450(scc) (CYP11A1) and P450(11 beta) (CYP11B1), thereby receiving electrons from bovine NADPH-dependent Adx reductase [13].
• However, the coexpression of bovine CYP11B1 and CYP11A1 in the presence of adrenodoxin resulted in a stimulation of 11beta-hydroxylation activity of CYP11B1 and in a decrease of the 18-hydroxycorticosterone and aldosterone formation [10].
• Steroid 11 beta-hydroxylase activity was inhibited by phenytoin [14].

Other interactions of CYP11B1

• To elucidate these QTL effects, animals from a German Holstein granddaughter design (18 families, 1,291 sons) were genotyped for CYP11B1 (V30A) and DGAT1 (K232A) polymorphisms [6].
• While the reduction of cytochrome c, reflecting the interaction between adrenodoxin and its reductase, and the interaction with CYP11B1 have not been significantly affected by the presence of the presequence, the binding affinity of preadrenodoxin to CYP11A1 is 5.5-fold lower than that of the mature form [15].

Analytical, diagnostic and therapeutic context of CYP11B1

• The interaction of bovine adrenodoxin with CYP11A1 (cytochrome P450scc) and CYP11B1 (cytochrome P45011beta ). Acceleration of reduction and substrate conversion by site-directed mutagenesis of adrenodoxin [2].
• The induction of steroid 11 beta-hydroxylase and 17 alpha-hydroxylase was studied in bovine adrenocortical cell cultures in serum-free medium [16].

References