Fast Motions in 5 Alpha Reductase and Its Impact on Enzyme Kinetics
May 2026
in “
ACS Catalysis
”
The study investigates the catalytic mechanism of steroid 5α-reductase type 2 (SRD5A2), focusing on the dynamic interactions among residues that affect enzyme kinetics. Using QM/MM simulations, it was found that residues Tyr33 and L224 compress the donor, altering free energy barriers and supporting the preorganization theory. Additionally, six other residues (Trp53, Arg94, Cys119, Glu197, Phe223, and Arg227) form a network that stabilizes transition states through electrostatic and structural interactions. The L224P mutant analysis shows that losing L224 compression increases energy barriers by 3.3-3.4 kcal/mol, highlighting the importance of dynamic and electrostatic coordination for efficient catalysis.