Afficher la couverture 'Structural Analysis of VDR Complex with ZK168281 Antagonist | Belorusova, Anna, y' en grand format
/5

0 avis

Structural Analysis of VDR Complex with ZK168281 Antagonist

Archive ouverte

Belorusova, Anna, y | Chalhoub, Sandra | Rovito, Daniela | Rochel, Natacha

Edité par CCSD ; American Chemical Society -

International audience. 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.

Suggestions

Du même auteur

Cytosolic sequestration of the vitamin D receptor as a therapeutic option for vitamin D-induced hypercalcemia

Archive ouverte | Rovito, Daniela | CCSD

International audience. The bioactive vitamin D3, 1α,25(OH)2D3, plays a central role in calcium homeostasis by controlling the activity of the vitamin D receptor (VDR) in various tissues. Hypercalcemia secondary to ...

Molecular determinants of MED1 interaction with the DNA bound VDR–RXR heterodimer

Archive ouverte | Belorusova Anna, Y | CCSD

International audience. The MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of cla...

A vitamin D‐based strategy overcomes chemoresistance in prostate cancer

Archive ouverte | Len‐tayon, Kateryna | CCSD

International audience. Background and purpose Castration‐resistant prostate cancer (CRPC) is a common male malignancy that requires new therapeutic strategies due to acquired resistance to its first‐line treatment,...

Chargement des enrichissements...