3a3z: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:3a3z.png|left|200px]]
-{{STRUCTURE_3a3z|  PDB=3a3z  |  SCENE=  }}
+==Crystal structure of the human VDR ligand binding domain bound to the synthetic agonist compound 2alpha-methyl-AMCR277A(C23S)==
+<StructureSection load='3a3z' size='340' side='right'caption='[[3a3z]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3a3z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A3Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A3Z 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]] 1.72&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2MV:(1S,2S,3R,5Z,7E,14BETA,17ALPHA)-17-[(2S,4S)-4-(2-HYDROXY-2-METHYLPROPYL)-2-METHYLTETRAHYDROFURAN-2-YL]-2-METHYL-9,10-SECOANDROSTA-5,7,10-TRIENE-1,3-DIOL'>2MV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3a3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a3z OCA], [https://pdbe.org/3a3z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a3z RCSB], [https://www.ebi.ac.uk/pdbsum/3a3z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a3z ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[https://omim.org/entry/277440 277440]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN] 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. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a3/3a3z_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3a3z ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1alpha,25(OH)(2)D(3) analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. We recently showed that the synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a) acts as a 1alpha,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1alpha,25(OH)(2)D(3), 2alpha-methyl-1alpha,25(OH)(2)D(3), or 2a, we designed a novel analogue, 2alpha-methyl-(20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.
-===Crystal structure of the human VDR ligand binding domain bound to the synthetic agonist compound 2alpha-methyl-AMCR277A(C23S)===
+Structure-Function Relationships and Crystal Structures of the Vitamin D Receptor Bound 2alpha-Methyl-(20S,23S)- and 2alpha-Methyl-(20S,23R)-epoxymethano-1alpha,25-dihydroxyvitamin D(3).,Antony P, Sigueiro R, Huet T, Sato Y, Ramalanjaona N, Rodrigues LC, Mourino A, Moras D, Rochel N J Med Chem. 2010 Jan 13. PMID:20070104<ref>PMID:20070104</ref>
-{{ABSTRACT_PUBMED_20070104}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3a3z" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[3a3z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A3Z OCA].
+*[[Sandbox vdr|Sandbox vdr]]
+*[[Vitamin D receptor|Vitamin D receptor]]
-==Reference==
+*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]]
-<ref group="xtra">PMID:020070104</ref><references group="xtra"/>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Antony, P.]]
+[[Category: Large Structures]]
-[[Category: Huet, T.]]
+[[Category: Antony P]]
-[[Category: Moras, D.]]
+[[Category: Huet T]]
-[[Category: Rochel, N.]]
+[[Category: Moras D]]
-[[Category: Sato, Y.]]
+[[Category: Rochel N]]
-[[Category: Sigueiro, R.]]
+[[Category: Sato Y]]
-[[Category: Gene regulation]]
+[[Category: Sigueiro R]]
-[[Category: Spine2]]
-[[Category: Structural genomic]]
-[[Category: Structural proteomics in europe 2]]
-[[Category: Transcription]]