Phenylalanine Residues in the Active Site of CYP2E1 Participate in Determining the Binding Orientation and Metabolism-Dependent Genotoxicity of Aromatic Compounds.

ABSTRACT: The composition of amino acids forming the active site of a CYP enzyme is impactful in its substrate selectivity. For CYP2E1, the role of PHE residues in the formation of effective binding orientations for its aromatic substrates remains unclear. In this study, molecular docking and molecular dynamics analysis were performed to reflect the interactions between PHEs in the active site of human CYP2E1 and various aromatic compounds known as its substrates. The results indicated that the orientation of 1-methylpyrene (1-MP) in the active site was highly determined by the presence of PHEs, PHE478 contributing to the binding free energy most significantly. Moreover, by building a random forest model the relationship between each of 19 molecular descriptors of polychlorinated biphenyl (PCB) comp

SUBMITTER: Hu K 

PROVIDER: S-EPMC10302094 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature