Redox partner adrenodoxin alters cytochrome P450 11B1 ligand binding and inhibition.

ABSTRACT: Human cytochrome P450 11B1 (CYP11B1) generation of the major glucocorticoid cortisol requires two electrons delivered sequentially by the iron‑sulfur protein adrenodoxin. While the expected adrenodoxin binding site is on the opposite side of the heme and 15-20 Å away, evidence is provided that adrenodoxin allosterically impacts CYP11B1 ligand binding and catalysis. The presence of adrenodoxin both decreases the dissociation constant (K_d) for substrate binding and increases the proportion of substrate that is bound at saturation. Adrenodoxin additionally decreases the Michaelis-Menten constant for the native substrate. Similar studies with several inhibitors also demonstrate the ability of adrenodoxin to modulate inhibition (IC₅₀ values). Somewhat similar allosterism h

SUBMITTER: Loomis CL 

PROVIDER: S-EPMC9907956 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature