9gyj
From Proteopedia
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(New page: '''Unreleased structure''' The entry 9gyj is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Vitamin D receptor in complex with Sila-c== | |
| + | <StructureSection load='9gyj' size='340' side='right'caption='[[9gyj]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9gyj]] 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=9GYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9GYJ 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]] 1.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IQN:(1~{R},3~{S},5~{Z})-5-[(2~{E})-2-[(1~{R},3~{a}~{S},7~{a}~{R})-7~{a}-methyl-1-[(2~{R})-5-trimethylsilylpent-4-yn-2-yl]-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol'>A1IQN</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=9gyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9gyj OCA], [https://pdbe.org/9gyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9gyj RCSB], [https://www.ebi.ac.uk/pdbsum/9gyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9gyj 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 == | ||
| + | The incorporation of silicon bioisosteres into pharmacological structures has been used as a strategy to improve the therapeutic potential of drugs. However, no secosteroidal silicon-containing VDR ligands have been developed. Here we report the design, synthesis, and biological activity of six analogues of the natural hormone 1,25-dihydroxyvitamin D3 (1,25D(3)), which incorporate a silicon atom as a side chain-C25 isostere. The analogues were synthesized by the Wittig-Horner approach starting from Inhoffen-Lythgoe diol. The crystal structures of the complexes formed by the sila-analogues with the ligand binding domain of VDR revealed additional interactions of the sila-containing side chains that stabilize the VDR active conformation. These sila-analogues show similar VDR binding and transcriptional activity in comparison with the natural hormone 1,25D(3), but with significantly less hypercalcemic activity. The new analogues, when combined with chemotherapy, significantly decrease cell proliferation. | ||
| - | + | First Sila-Vitamin D Analogues: Design, Synthesis, Structural Analysis and Biological Activity.,Loureiro J, Seoane S, Sampaio-Dias IE, Peluso-Iltis C, Guiberteau T, Brito B, Gregorio C, Perez-Fernandez R, Rochel N, Mourino A, Rodriguez-Borges JE J Med Chem. 2024 Nov 29. doi: 10.1021/acs.jmedchem.4c02404. PMID:39610329<ref>PMID:39610329</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9gyj" 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 in complex with Sila-c
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