Structure-guided approach to modulate small molecule binding to a promiscuous ligand-activated protein.

ABSTRACT: Ligand-binding promiscuity in detoxification systems protects the body from toxicological harm but is a roadblock to drug development due to the difficulty in optimizing small molecules to both retain target potency and avoid metabolic events. Immense effort is invested in evaluating metabolism of molecules to develop safer, more effective treatments, but engineering specificity into or out of promiscuous proteins and their ligands is a challenging task. To better understand the promiscuous nature of detoxification networks, we have used X-ray crystallography to characterize a structural feature of pregnane X receptor (PXR), a nuclear receptor that is activated by diverse molecules (with different structures and sizes) to up-regulate transcription of drug metabolism genes. We found that la

SUBMITTER: Lin W 

PROVIDER: S-EPMC10013835 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature