A Structural and Dynamic Perspective on Xenobiotic Metabolism by Cytochrome P450.
- 1Department of Chemistry, School of Natural Sciences, Shiv Nadar Institution of Eminence, Greater Noida, Uttar Pradesh 201314, India.
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.
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BibTeX
@article{bhatt2026structural,
title = {{A Structural and Dynamic Perspective on Xenobiotic Metabolism by Cytochrome P450.}},
author = {Vaibhav Bhatt and Kshatresh Dutta Dubey},
journal = {ACS bio \& med chem Au},
year = {2026},
month = jul,
doi = {10.1021/acsbiomedchemau.6c00119},
url = {https://europepmc.org/article/MED/42921044},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A Structural and Dynamic Perspective on Xenobiotic Metabolism by Cytochrome P450.
AU - Vaibhav Bhatt
AU - Kshatresh Dutta Dubey
PY - 2026
DA - 2026/07/27
JO - ACS bio & med chem Au
DO - 10.1021/acsbiomedchemau.6c00119
UR - https://europepmc.org/article/MED/42921044
AB - 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.
SN - 2694-2437
ER -