Structural basis for cooperative binding of azoles to CYP2E1 as interpreted through guided molecular dynamics simulations.

ABSTRACT: CYP2E1 metabolizes a wide array of small, hydrophobic molecules, resulting in their detoxification or activation into carcinogens through Michaelis-Menten as well as cooperative mechanisms. Nevertheless, the molecular determinants for CYP2E1 specificity and metabolic efficiency toward these compounds are still unknown. Herein, we employed computational docking studies coupled to molecular dynamics simulations to provide a critical perspective for understanding a structural basis for cooperativity observed for an array of azoles from our previous binding and catalytic studies (Hartman et al., 2014). The resulting 28 CYP2E1 complexes in this study revealed a common passageway for azoles that included a hydrophobic steric barrier causing a pause in movement toward the active site. The entranc

SUBMITTER: Levy JW 

PROVIDER: S-EPMC4314338 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature