Document Report Card

Basic Information

ID: ALA4619805

Journal: J Med Chem

Title: Structural Analysis of VDR Complex with ZK168281 Antagonist.

Authors: Belorusova AY, Chalhoub S, Rovito D, Rochel N.

Abstract: Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1α,25-dihydroxyvitamin D3. Here, we report the crystal structure of the zebrafish VDR ligand-binding domain in complex with the ZK168281 antagonist, revealing that the ligand prevents optimal folding of the C-terminal region of VDR. This interference was confirmed by hydrogen-deuterium exchange mass spectrometry (HDX-MS) in solution.

CiteXplore: 32787090

DOI: 10.1021/acs.jmedchem.0c00656