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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Belorusova AY,Chalhoub S,Rovito D,Rochel Ndoi
10.1021/acs.jmedchem.0c00656subject
Has Abstractpub_date
2020-09-10 00:00:00pages
9457-9463issue
17eissn
0022-2623issn
1520-4804journal_volume
63pub_type
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