Structure of Human Steroid 5α-Reductase 2 with Anti-Androgen Drug Finasteride

July 2020 in “ Research Square (Research Square) ”

Qingpin Xiao, Lei Wang, Shreyas Supekar, Tao Shen, Heng Liu, Fei Ye, Junzhou Huang, Hao Fan, Zhiyi Wei, Cheng Zhang

finasteride steroid 5α-reductase 2 testosterone 5α-reduction NADPH E57 Y91 integral membrane steroid reductases Propecia

TLDR The research helps understand how finasteride works and aids drug development.

The study reported the crystal structure of human steroid 5α-reductase 2 (SRD5α2) at 2.8 Å, revealing a unique 7-transmembrane structural topology and an intermediate adduct of finasteride and NADPH in a binding cavity. This provided insights into the molecular mechanisms of testosterone 5α-reduction and finasteride inhibition, involving key residues E57 and Y91. The research also mapped disease-causing mutations to the structure, suggesting mechanisms for their effects, and highlighted the enzyme's conformational dynamics. These findings offered critical insights into the function of integral membrane steroid reductases and aimed to facilitate drug development.

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