9rcg
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Vitamin D receptor complex with a vitamin D receptor agonist/histone deacetylase inhibitor hybrid molecule== | |
| + | <StructureSection load='9rcg' size='340' side='right'caption='[[9rcg]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9rcg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9RCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RCG FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JD5:4-[4-[3-[5-[(3~{S})-4,4-dimethyl-3-oxidanyl-pentyl]-4-methyl-1,3-thiazol-2-yl]pentan-3-yl]phenoxy]-~{N}-oxidanyl-butanamide'>A1JD5</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9rcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rcg OCA], [https://pdbe.org/9rcg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rcg RCSB], [https://www.ebi.ac.uk/pdbsum/9rcg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rcg ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/VDRA_DANRE VDRA_DANRE] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Plays a central role in calcium homeostasis.<ref>PMID:17218092</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 1,25-Dihydroxyvitamin D (1,25D) analogs engage the vitamin D receptor (VDR) and can exert anticancer and immunomodulatory effects. Although tumors often resist 1,25D monotherapy, combining VDR agonism with histone deacetylase inhibitors (HDACi) restores anticancer efficacy. Here, we present AC-340, a novel bifunctional molecule that incorporates HDACi into a VDR agonist backbone. Besides its robust bifunctionality in vitro in multiple melanoma models, RNaseq analysis of B16-F10 mouse melanoma cells revealed that AC-340 superinduces the expression of a broad array of VDR target genes. Comparative structural studies and ChIP-qPCR revealed that AC-340 forms more interactions than 1,25D with residues in the VDR coactivator binding domain, leading to more efficacious recruitment of coactivator CBP. This, likely coupled with AC-340 HDACi activity, leads to elevated H3K27 acetylation of VDR target genes, a mark of active transcription. Thus, AC-340 functions as a VDR hyperagonist and should be efficacious in mono- or combination therapies against multiple cancer models. | ||
| - | + | Hyperagonism of a Vitamin D Receptor Agonist/Histone Deacetylase Inhibitor Hybrid Molecule.,Sarmadi F, Caza A, Gao Z, Rochel N, Gleason JL, White JH J Med Chem. 2025 Sep 18. doi: 10.1021/acs.jmedchem.5c01932. PMID:40968099<ref>PMID:40968099</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9rcg" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Danio rerio]] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rochel N]] | ||
Current revision
Vitamin D receptor complex with a vitamin D receptor agonist/histone deacetylase inhibitor hybrid molecule
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