6T2M

VDR-ZK168281 complex

Summary for 6T2M

• Entry DOI: 10.2210/pdb6t2m/pdb
• Descriptor: Vitamin D3 receptor A, Nuclear receptor coactivator 1, ethyl (~{Z})-3-[1-[(~{E},1~{R},4~{R})-4-[(1~{R},3~{a}~{S},4~{E},7~{a}~{R})-7~{a}-methyl-4-[(2~{Z})-2-[(3~{S},5~{R})-2-methylidene-3,5-bis(oxidanyl)cyclohexylidene]ethylidene]-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-1-yl]-1-oxidanyl-pent-2-enyl]cyclopropyl]prop-2-enoate, ... (4 entities in total)
• Functional Keywords: nuclear receptor, complex, transcription
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 2
• Total formula weight: 36347.45

Authors

Rochel, N.,Belorusova, A.Y. (deposition date: 2019-10-09, release date: 2020-08-26, Last modification date: 2024-01-24)

Primary citation

Belorusova, A.Y.,Chalhoub, S.,Rovito, D.,Rochel, N.
Structural Analysis of VDR Complex with ZK168281 Antagonist.
J.Med.Chem., 63:9457-9463, 2020

PubMed 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.

PubMed: 32787090
DOI: 10.1021/acs.jmedchem.0c00656

Experimental method

X-RAY DIFFRACTION (3 Å)