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==Crystal structure of the human vitamin D receptor ligand binding domain complexed with 1alpha,25-Dihydroxy-2alpha-[2-(2H-tetrazol-2-yl)ethyl]vitamin D3== | |||
<StructureSection load='4ite' size='340' side='right' caption='[[4ite]], [[Resolution|resolution]] 2.49Å' scene=''> | |||
== Structural highlights == | |||
==Disease== | <table><tr><td colspan='2'>[[4ite]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ITE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ITE FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TEY:(1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3AS,7AR)-7A-METHYL-1-[(2R)-6-METHYL-6-OXIDANYL-HEPTAN-2-YL]-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-4-METHYLIDENE-2-[2-(1,2,3,4-TETRAZOL-2-YL)ETHYL]CYCLOHEXANE-1,3-DIOL'>TEY</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4itf|4itf]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VDR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ite FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ite OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ite RCSB], [http://www.ebi.ac.uk/pdbsum/4ite PDBsum]</span></td></tr> | |||
<table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://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> | [[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://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 == | |||
==Function== | |||
[[http://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> | [[http://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 == | |||
2alpha-Heteroarylethyl-1alpha,25-dihydroxyvitamin D3 analogues, which were designed to form a hydrogen bond between Arg274 of human vitamin D receptor (hVDR) and a nitrogen atom of the heteroaromatic ring at the 2alpha-position, were synthesized. Among them, 2alpha-[2-(tetrazol-2-yl)ethyl]-1alpha,25-dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats, osteoporosis model animals, on enhancing bone mineral density than those of active vitamin D3. X-ray cocrystallographic analysis of the hVDR-ligand complex confirms that the new hydrogen bond formation stabilized the complex. | |||
Synthesis of 2alpha-heteroarylalkyl active vitamin d3 with therapeutic effect on enhancing bone mineral density in vivo.,Matsuo M, Hasegawa A, Takano M, Saito H, Kakuda S, Chida T, Takagi K, Ochiai E, Horie K, Harada Y, Takimoto-Kamimura M, Takenouchi K, Sawada D, Kittaka A ACS Med Chem Lett. 2013 May 28;4(7):671-4. doi: 10.1021/ml400098w. eCollection, 2013 Jul 11. PMID:24900728<ref>PMID:24900728</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
<references | </div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: Kakuda, S.]] | [[Category: Kakuda, S.]] | ||
[[Category: Takimoto-Kamimura, M.]] | [[Category: Takimoto-Kamimura, M.]] | ||
[[Category: Hormone receptor]] | [[Category: Hormone receptor]] | ||
[[Category: Transcription]] | [[Category: Transcription]] | ||