Human and murine steroid 5β-reductases (AKR1D1 and AKR1D4): insights into the role of the catalytic glutamic acid.

ABSTRACT: Mammalian steroid 5β-reductases belong to the Aldo-Keto Reductase 1D sub-family and are essential for the formation of A-ring 5β-reduced steroids. Steroid 5β-reduction is required for the biosynthesis of bile-acids and the metabolism of all steroid hormones that contain a Δ⁴-3-ketosteroid functionally to yield the 5β-reduced metabolites. In mammalian AKR1D enzymes the conserved catalytic tetrad found in all AKRs (Y55, H117, K84 and D50) has changed in that the conserved H117 is replaced with a glutamic acid (E120). E120 may act as a "superacid" to facilitate enolization of the Δ⁴-ketosteroid. In addition, the absence of the bulky imidazole side chain of histidine in E120 permits the steroid to penetrate deeper into the active site so that hydride transfer can occur to

SUBMITTER: Chen M 

PROVIDER: S-EPMC6500757 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature