2.A.90.3.6
The human steroid 5alpha-reductase 2 of 254 aas and 7 TMSs.  The x-ray structure has been determined to 2.8 Å with the anti-androgen drug finasteride bound (Xiao et al. 2020). It catalyzes the reduction of testosterone to dihydrotestosterone, and mutations in the SRD5A2 gene have been linked to 5alpha-reductase deficiency and prostate cancer. Finasteride and dutasteride, as SRD5A2 inhibitors, are widely used antiandrogen drugs for benign prostate hyperplasia. Xiao et al. 2020 showed a unique 7-TMS topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the transmembrane domain. Structural analysis together with computational and mutagenesis studies reveal the molecular mechanisms of the catalyzed reaction and of finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicated  conformational dynamics of the cytosolic region that regulate NADPH/NADP(+) exchange (Xiao et al. 2020).