Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations
| dc.contributor.author | Guengerich, F. Peter | |
| dc.contributor.author | Tateishi, Yasuhiro | |
| dc.contributor.author | McCarty, Kevin D. | |
| dc.contributor.author | Yoshimoto, Francis K. | |
| dc.date.accessioned | 2024-08-28T14:00:14Z | |
| dc.date.available | 2024-08-28T14:00:14Z | |
| dc.date.issued | 2024-08-20 | |
| dc.date.updated | 2024-08-28T14:00:14Z | |
| dc.description.abstract | Cytochrome P450 (P450) enzymes dominate steroid metabolism. In general, the simple C-hydroxylation reactions are mechanistically straightforward and are generally agreed to involve a perferryl oxygen species (formally FeO<sup>3+</sup>). Several of the steroid transformations are more complex and involve C-C bond scission. We initiated mechanistic studies with several of these (i.e., 11A1, 17A1, 19A1, and 51A1) and have now established that the dominant modes of catalysis for P450s 19A1 and 51A1 involve a ferric peroxide anion (i.e., Fe<sup>3+</sup>O<sub>2</sub>¯) instead of a perferryl ion complex (FeO<sup>3+</sup>), as demonstrated with <sup>18</sup>O incorporation studies. P450 17A1 is less clear. The indicated P450 reactions all involve sequential oxidations, and we have explored the processivity of these multi-step reactions. P450 19A1 is distributive, i.e., intermediate products dissociate and reassociate, but P450s 11A1 and 51A1 are highly processive. P450 17A1 shows intermediate processivity, as expected from the release of 17-hydroxysteroids for the biosynthesis of key molecules, and P450 19A1 is very distributive. P450 11B2 catalyzes a processive multi-step oxidation process with the complexity of a chemical closure of an intermediate to a locked lactol form. | |
| dc.identifier | doi: 10.3390/ijms25169020 | |
| dc.identifier.citation | International Journal of Molecular Sciences 25 (16): 9020 (2024) | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12588/6614 | |
| dc.title | Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations |