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5xzf
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Vitamin D receptor with a synthetic ligand ADRO1== | |
| + | <StructureSection load='5xzf' size='340' side='right'caption='[[5xzf]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5xzf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XZF 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=8J0:(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,6S)-6-(1-adamantyl)-6-oxidanyl-hex-4-yn-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol'>8J0</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=5xzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xzf OCA], [https://pdbe.org/5xzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xzf RCSB], [https://www.ebi.ac.uk/pdbsum/5xzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xzf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Both 25 R- and 25 S-25-adamantyl-23-yne-26,27-dinor-1alpha,25-dihydroxyvitamin D3 (4a and 4b) were stereoselectively synthesized by a Pd(0)-catalyzed ring closure and Suzuki-Miyaura coupling between enol-triflate 7 and alkenyl-boronic ester 8. The 25 S isomer (4b) showed high vitamin D receptor (VDR) affinity (50% of that of the natural hormone 1alpha,25-dihydroxyvitamin D3, 1) and transactivation potency (kidney HEK293, 90%). In endogenous gene expression, it showed high cell-type selectivity for kidney cells (HEK293, CYP24A1 160% of 1), bone cells (MG63, osteocalcin 64%), and monocytes (U937, CAMP 96%) over intestine (SW480, CYP24A1 8%) and skin (HaCaT, CYP24A1 7%) cells. The X-ray crystal structural analysis of 4b in complex with rat VDR-ligand binding domain (LBD) showed the highest Calpha positional shift from the 1/VDR-LBD complex at helix 11. Helix 11 of the 4b and 1 VDR-LBD complexes also showed significant differences in surface properties. These results suggest that 4b should be examined further as another candidate for a mild preventive osteoporosis agent. | ||
| - | + | 25 S-Adamantyl-23-yne-26,27-dinor-1alpha,25-dihydroxyvitamin D3: Synthesis, Tissue Selective Biological Activities, and X-ray Crystal Structural Analysis of Its Vitamin D Receptor Complex.,Otero R, Ishizawa M, Numoto N, Ikura T, Ito N, Tokiwa H, Mourino A, Makishima M, Yamada S J Med Chem. 2018 Jul 23. doi: 10.1021/acs.jmedchem.8b00427. PMID:29989817<ref>PMID:29989817</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5xzf" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]] |
| - | [[Category: Numoto | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Ikura T]] | ||
| + | [[Category: Ito N]] | ||
| + | [[Category: Makishima M]] | ||
| + | [[Category: Mourino A]] | ||
| + | [[Category: Numoto N]] | ||
| + | [[Category: Otero R]] | ||
| + | [[Category: Yamada S]] | ||
Current revision
Vitamin D receptor with a synthetic ligand ADRO1
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Categories: Homo sapiens | Large Structures | Rattus norvegicus | Ikura T | Ito N | Makishima M | Mourino A | Numoto N | Otero R | Yamada S
