7b39: Difference between revisions
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==== | ==Allene-Based Design of a Noncalcemic Vitamin D Receptor Agonist== | ||
<StructureSection load='7b39' size='340' side='right'caption='[[7b39]]' scene=''> | <StructureSection load='7b39' size='340' side='right'caption='[[7b39]], [[Resolution|resolution]] 2.13Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7b39]] 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=7B39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B39 FirstGlance]. <br> | ||
</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=7b39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b39 OCA], [https://pdbe.org/7b39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b39 RCSB], [https://www.ebi.ac.uk/pdbsum/7b39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b39 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.13Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=T0H:(1R,3S,Z)-5-(2-((3aS,7aS,E)-1-(6-hydroxy-6-methylhept-1-en-1-ylidene)-7a-methyloctahydro-4H-inden-4-ylidene)ethylidene)-4-methylenecyclohexane-1,3-diol'>T0H</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=7b39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b39 OCA], [https://pdbe.org/7b39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b39 RCSB], [https://www.ebi.ac.uk/pdbsum/7b39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b39 ProSAT]</span></td></tr> | |||
</table> | </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 == | |||
Vitamin D receptor ligands have potential for the treatment of hyperproliferative diseases and disorders related to the immune system. However, hypercalcemic effects limit their therapeutical uses and call for the development of tissue-selective new analogs. We have designed and synthesized the first examples of 1alpha,25-dihydroxyvitamin D(3) analogs bearing an allenic unit attached to the D ring to restrict the side-chain conformational mobility. The triene system was constructed by a Pd(0) -mediated cyclization/Suzuki-Miyaura cross-coupling process in the presence of an allenic side chain. The allenic moiety was built through an orthoester-Claisen rearrangement of a propargylic alcohol. The biological activity and structure of (22S)-1alpha,25-dihydroxy-17,20-dien-24-homo-21-nor-vitamin D(3) bound to binding domain of the vitamin D receptor, provide information concerning side-chain conformational requirements for biological activity. | |||
Design, Synthesis, Evaluation and Structure of Allenic 1alpha,25-Dihydroxyvitamin D(3) Analogs with Locked Mobility at C-17.,Fraga R, Len K, Lutzing R, Laverny G, Loureiro J, Maestro MA, Rochel N, Rodriguez-Borges E, Mourino A Chemistry. 2021 Sep 20;27(53):13384-13389. doi: 10.1002/chem.202101578. Epub 2021 , Aug 11. PMID:34224173<ref>PMID:34224173</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7b39" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Danio rerio]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Rochel N]] | ||
Latest revision as of 15:21, 1 February 2024
Allene-Based Design of a Noncalcemic Vitamin D Receptor AgonistAllene-Based Design of a Noncalcemic Vitamin D Receptor Agonist
Structural highlights
FunctionVDRA_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.[1] Publication Abstract from PubMedVitamin D receptor ligands have potential for the treatment of hyperproliferative diseases and disorders related to the immune system. However, hypercalcemic effects limit their therapeutical uses and call for the development of tissue-selective new analogs. We have designed and synthesized the first examples of 1alpha,25-dihydroxyvitamin D(3) analogs bearing an allenic unit attached to the D ring to restrict the side-chain conformational mobility. The triene system was constructed by a Pd(0) -mediated cyclization/Suzuki-Miyaura cross-coupling process in the presence of an allenic side chain. The allenic moiety was built through an orthoester-Claisen rearrangement of a propargylic alcohol. The biological activity and structure of (22S)-1alpha,25-dihydroxy-17,20-dien-24-homo-21-nor-vitamin D(3) bound to binding domain of the vitamin D receptor, provide information concerning side-chain conformational requirements for biological activity. Design, Synthesis, Evaluation and Structure of Allenic 1alpha,25-Dihydroxyvitamin D(3) Analogs with Locked Mobility at C-17.,Fraga R, Len K, Lutzing R, Laverny G, Loureiro J, Maestro MA, Rochel N, Rodriguez-Borges E, Mourino A Chemistry. 2021 Sep 20;27(53):13384-13389. doi: 10.1002/chem.202101578. Epub 2021 , Aug 11. PMID:34224173[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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