3vhw: Difference between revisions
New page: '''Unreleased structure''' The entry 3vhw is ON HOLD Authors: Kakuda, S., Takimoto-Kamimura, M. Description: Crystal structure of the human vitamin D receptor ligand binding domain com... |
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==Crystal structure of the human vitamin D receptor ligand binding domain complexed with 4-MP== | |||
<StructureSection load='3vhw' size='340' side='right'caption='[[3vhw]], [[Resolution|resolution]] 2.43Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3vhw]] 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=3VHW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VHW 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]] 2.43Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VHW:methyl+(1S,3E)-3-{(2R)-2-[(1R,3aS,4E,7aR)-4-{(2Z)-2-[(3R,4S,5R)-3,5-dihydroxy-4-(3-hydroxypropoxy)-2-methylidenecyclohexylidene]ethylidene}-7a-methyloctahydro-1H-inden-1-yl]propylidene}-1-ethyl-2-oxocyclopentanecarboxylate+(non-preferred+name)'>VHW</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=3vhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vhw OCA], [https://pdbe.org/3vhw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vhw RCSB], [https://www.ebi.ac.uk/pdbsum/3vhw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vhw 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Up to the present, numerous vitamin D derivatives have been synthesized, but most of them have straight side chains, and there are few publications described about in vitro and in vivo evaluations on bone by vitamin D derivatives. In our previous paper, we reported the synthesis of various C-2 substituted vitamin D derivatives (2b-2i) with a 2,2-dimethylcyclopentanone unit in the CD-ring side chains, and that the derivatives have strong activity for enhancing bone growth. On the basis of results, this time, we report the synthesis of 2alpha-substituted vitamin D(3) derivatives with chiral cyclopentanone (3-6 and 12-16). These derivatives were obtained by Pd-coupling reaction with A-ring precursor and CD-rings precursor. We evaluated novel derivatives in vitro assays, for affinities for VDR and transactivation assays by human osteosarcoma (HOS) cells. In this research, we demonstrated that some novel vitamin D derivatives (12-MP, 13-MP, 15-MP and 16-LP) have strong transactivation activities in spite of lower affinity for VDR than 1. In addition, we also demonstrated that these derivatives have strong activities for enhancing bone growth using OVX therapeutic rats. This article is part of a Special Issue entitled 'Vitamin D Workshop'. | |||
Synthesis of novel C-2 substituted vitamin D derivatives having ringed side chains and their biological evaluation on bone.,Saito H, Takagi K, Horie K, Kakuda S, Takimoto-Kamimura M, Ochiai E, Chida T, Harada Y, Takenouchi K, Kittaka A J Steroid Biochem Mol Biol. 2013 Feb 13. pii: S0960-0760(13)00025-3. doi:, 10.1016/j.jsbmb.2013.02.004. PMID:23416104<ref>PMID:23416104</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3vhw" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sandbox vdr|Sandbox vdr]] | |||
*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Kakuda S]] | |||
[[Category: Takimoto-Kamimura M]] | |||