9FBF

VDR complex with UG-481

This is a non-PDB format compatible entry.

Summary for 9FBF

• Entry DOI: 10.2210/pdb9fbf/pdb
• Descriptor: Vitamin D3 receptor A, Nuclear receptor coactivator 1, (1~{R},3~{S},5~{Z})-5-[(2~{E})-2-[(1~{R},3~{a}~{S},7~{a}~{R})-7~{a}-methyl-1-[(1~{S})-5-methyl-1-[(1~{R},2~{R})-2-(3-methyl-3-oxidanyl-butyl)cyclopropyl]-5-oxidanyl-hexyl]-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol, ... (4 entities in total)
• Functional Keywords: vitamin d receptor, agonist, transcription
• Biological source: Danio rerio (zebrafish); More
• Total number of polymer chains: 2
• Total formula weight: 36365.55

Authors

Rochel, N. (deposition date: 2024-05-13, release date: 2024-06-19, Last modification date: 2024-07-10)

Primary citation

Gomez-Bouzo, U.,Peluso-Iltis, C.,Santalla, H.,Quevedo, M.A.,Verlinden, L.,Verstuyf, A.,Fall, Y.,Gomez, G.,Rochel, N.
Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain.
J.Med.Chem., 67:10386-10400, 2024

PubMed Abstract: We synthesized two new gemini analogues, and , that incorporate a modified longer side chain containing a cyclopropane group. The evaluation of the bioactivities of the two gemini analogues indicated that the 17,20 threo (20) compound, , is the most active one and is as active as 1,25(OH)D. Docking and molecular dynamics (MD) data showed that the compounds bind efficiently to vitamin D receptor (VDR) with to form an energetically more favorable interaction with His397. Structural analysis indicated that whereas the compound efficiently stabilizes the active VDR conformation, it induces conformational changes in the H6-H7 VDR region that are greater than those induced by the parental Gemini and that this is due to the occupancy of the secondary channel by its modified side chain.

PubMed: 38858308
DOI: 10.1021/acs.jmedchem.4c00854

Experimental method

X-RAY DIFFRACTION (3.01 Å)