The human steroid hydroxylases CYP1B1 and CYP11B2.
Major advances have been made during the last decade in our understanding of adrenal steroid hormone biosynthesis. Two key players in these pathways are the human mitochondrial cytochrome P450 enzymes CYP11B1 and CYP11B2, which catalyze the final steps in the biosynthesis of cortisol and aldosterone. Using data from mutations found in patients suffering from steroid hormone-related diseases, from mutagenesis studies and from the construction of three-dimensional models of these enzymes, structural information could be deduced that provide a clue to the stereo- and regiospecific steroid hydroxylation reactions carried out by these enzymes. In this review, we summarize the current knowledge on the physiological function and the biochemistry of these enzymes. Furthermore, the pharmacological and toxicological importance of these steroid hydroxylases, the means for the identification of their potential inhibitors and possible biotechnological applications are discussed.
Bureik
Matthias
M
Universität des Saarlandes, FR 8.8 Biochemie, Postfach 151150, D-66041 Saarbrücken, Germany.
Lisurek
Michael
M
Bernhardt
Rita
R
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase