Conformational Characterization of the Co-Activator Binding Site Revealed the Mechanism to Achieve the Bioactive State of FXR.

ABSTRACT: FXR bioactive states are responsible for the regulation of metabolic pathways, which are modulated by agonists and co-activators. The synergy between agonist binding and 'co-activator' recruitment is highly conformationally driven. The characterization of conformational dynamics is essential for mechanistic and therapeutic understanding. To shed light on the conformational ensembles, dynamics, and structural determinants that govern the activation process of FXR, molecular dynamic (MD) simulation is employed. Atomic insights into the ligand binding domain (LBD) of FXR revealed significant differences in inter/intra molecular bonding patterns, leading to structural anomalies in different systems of FXR. The sole presence of an agonist or 'co-activator' fails to achieve the essential bioacti

SUBMITTER: Kumari A 

PROVIDER: S-EPMC8439381 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature