Optical annealing of peroxo-ferric intermediates in CYP17A1 and product formation.

ABSTRACT: Human cytochrome P450 CYP17A1 catalyzes the hydroxylation of pregnenolone and progesterone at the C17 position, with subsequent C17-C20 bond scission, to form dehydroepiandrosterone and androstenedione respectively. The first hydroxylation reaction is faster in H₂O than in D₂O, while the second carbon‑carbon bond scission event demonstrates an inverse solvent isotope effect, which is more pronounced for 17-hydroxy pregnenolone. In order to better understand the cause of this difference, we compared the optical absorption spectra of oxygenated CYP17A1 with the four substrates (pregnenolone, progesterone, 17-hydroxy pregnenolone and 17-hydroxy progesterone) in both H₂O and D₂O. We also studied the temperature-dependent decay of the peroxo-ferric an

SUBMITTER: Denisov IG 

PROVIDER: S-EPMC11758937 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature