Abstract
Cytochrome P450 17A1 (CYP17A1) catalyzes the synthesis of androgens from the steroid precursors pregnenolone and progesterone in a two-step reaction process: allylic hydroxylation and carbo-carbon bond scission. Cytochrome b5 (Cyt-b5) is a stimulator of the second lyase reaction, but the chemical mechanism is unclear. We have shown previously that this stimulatory effect requires redox active Cyt-b5. To investigate the origin of the lyase reaction enhancement by electron transfer from Cyt-b5, we measured the reduction rates of oxy-ferrous substrate-bound CYP17A1 by Cyt-b5 and by cytochrome P450 reductase (CPR) coincorporated in Nanodiscs using stopped flow spectroscopy. We observed that Cyt-b5 reduces oxy-ferrous CYP17A1 10-fold faster than CPR, with the rate similar to that observed in a ternary complex of all three proteins.
Original language | English (US) |
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Pages (from-to) | 2282-2288 |
Number of pages | 7 |
Journal | FEBS Letters |
Volume | 592 |
Issue number | 13 |
DOIs | |
State | Published - Jul 2018 |
Keywords
- Nanodisc
- androgen biosynthesis
- cytochrome P450
- cytochrome b5
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology