Structural Analysis of VDR Complex with ZK168281 Antagonist

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.