CW EPR parameters reveal cytochrome P450 ligand binding modes.

ABSTRACT: Cytochrome P450 (CYP) monoxygenses utilize heme cofactors to catalyze oxidation reactions. They play a critical role in metabolism of many classes of drugs, are an attractive target for drug development, and mediate several prominent drug interactions. Many substrates and inhibitors alter the spin state of the ferric heme by displacing the heme's axial water ligand in the resting enzyme to yield a five-coordinate iron complex, or they replace the axial water to yield a nitrogen-ligated six-coordinate iron complex, which are traditionally assigned by UV-vis spectroscopy. However, crystal structures and recent pulsed electron paramagnetic resonance (EPR) studies find a few cases where molecules hydrogen bond to the axial water. The water-bridged drug-H₂O-heme has UV-vis spectra si

SUBMITTER: Lockart MM 

PROVIDER: S-EPMC5921899 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature