HSD11B1 Protein, Human (His-SUMO)

HSD11B1 protein governs the reversible conversion of biologically active glucocorticoids, such as cortisone to cortisol, and 11-dehydrocorticosterone to corticosterone, in the presence of NADP(H). This enzymatic activity is crucial for the corticosteroid receptor-mediated anti-inflammatory response, as well as metabolic and homeostatic processes. Additionally, HSD11B1 plays a role in the secretion of aqueous humor in the eye, contributing to the maintenance of a normotensive, intraocular environment. While displaying bidirectional capabilities in vitro, it predominantly functions as a reductase in vivo, thereby increasing the concentration of active glucocorticoids. The enzyme exhibits broad substrate specificity, accepting various steroid and sterol substrates. Notably, it interconverts 7-oxo- and 7-hydroxy-neurosteroids, such as 7-oxopregnenolone and 7beta-hydroxypregnenolone, 7-oxodehydroepiandrosterone and 7beta-hydroxydehydroepiandrosterone, among others. Furthermore, HSD11B1 catalyzes the stereo-specific conversion of the major dietary oxysterol, 7-ketocholesterol, into the more polar 7-beta-hydroxycholesterol metabolite, a process with implications in apoptosis, atherosclerotic lesions, lipid peroxidation, and foam cell formation. Moreover, it mediates the 7-oxo reduction of 7-oxolithocholate, providing a link between glucocorticoid activation and bile acid metabolism, ultimately influencing immune cell migration through the synthesis of 7-beta-25-dihydroxycholesterol, a ligand for the G-protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2).