Four-Amino Acid Segment in Steroid 5 Alpha-Reductase 1 Confers Sensitivity to Finasteride, a Competitive Inhibitor

    April 1992 in “ Journal of Biological Chemistry ”
    Anice E. Thigpen, David H. Russell
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    TLDR Four-amino acid part makes enzyme sensitive to finasteride.
    This study from 31 years ago found that a specific four-amino acid sequence in the steroid 5 alpha-reductase 1 enzyme is responsible for its sensitivity to finasteride, a competitive inhibitor. The sequence is composed of mostly hydrophobic amino acids and is located in the substrate-binding domain of the enzyme. The study also found that the rat and human type 1 enzymes are equally sensitive to 4-MA, a 4-azasteroid that differs from finasteride. The study suggests that the large phenylalanine side chain at position 3 of the human type 1 tetrapeptide sequence may represent the most likely single amino acid determinant of resistance.
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