A Structural and Dynamic Perspective on Xenobiotic Metabolism by Cytochrome P450
Year: 2026
Type: review
Abstract: Xenobiotic detoxification is the biotransformation of exogenous compounds entering the human body through enzymatic catalysis in order to assist their eventual elimination. In the past, static active-site models that mainly focus on substrate binding and oxidation chemistry have been employed to understand the xenobiotic functionality of CYP450s. However, modern computational approaches in the field of enzymology have changed this perspective, which show that the P450 machinery utilizes significant structural flexibility and electrostatic control to achieve its function. This review aims to unify these developments into an integrated mechanistic framework that encompasses substrate orientation, conformational gating, catalytic-site organization, transient water-channel assembly, and modulation of the electronic-structure landscape via classical electrostatic and steric confinement. Special focus has been given on how flexible loops/helices, gating residues, transient access channels, along with second-shell residues, dictate xenobiotic accommodation, regio-, stereo-, and chemoselectivity across various members of the CYP450 superfamily.
Source: ACS Bio & Med Chem Au
Authors: Vaibhav Bhatt, Kshatresh Dutta Dubey
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funder: Shiv Nadar Foundation
OpenAlex ID: W7172392386