Molecular biology of rat steroid 11 beta-hydroxylase [P450(11 beta)] and aldosterone synthase [P450(11 beta, aldo)].
The molecular features of rat steroid 11 beta-hydroxylase [P450(11 beta)] and aldosterone synthase [P450(11 beta, aldo)] are discussed. P450(11 beta) is biosynthesized as a precursor form composed of 499 amino acids, having a 24-amino acid extension peptide. Two species of P450(11 beta, aldo) were identified; a precursor form of P450(11 beta, aldo)-1 is 510 amino acids long and has a 34-amino acid extension peptide, while that of P450(11 beta, aldo)-2 is 500 amino acids long and has a 24-amino acid extension peptide. The 286th amino acid of P450(11 beta, aldo)-1 is Glu, while that of P450(11 beta, aldo)-2 is Lys. The cDNA-expression studies showed that P450(11 beta, aldo)-1 had the aldosterone producing activity whereas P450(11 beta, aldo)-2 had no activity, suggesting that Glu286 of P450(11 beta, aldo) plays an important role in the catalysis. The amino acid sequence of a region in P450(11 beta) from Leu337 through Pro352 is highly conserved among the steroidogenic P450s. Functional expression studies on the cDNAs for two P450(11 beta)s showed that P450(11 beta) catalyzes the 11 beta-, 18- and 19-hydroxylations of 11-deoxycorticosterone, but not the aldosterone synthesis. P450(11 beta, aldo), on the other hand, catalyzes the conversion of 11-deoxycorticosterone to corticosterone, 18-hydroxycorticosterone and aldosterone. The two P450(11 beta)s were also shown to catalyze the conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol and cortisone.
Okamoto
M
M
Department of Molecular Physiological Chemistry, Osaka University Medical School, Japan.
Nonaka
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D003001:Cloning, Molecular; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase