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5xpn

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Revision as of 06:56, 14 October 2020

Crystal structure of VDR-LBD complexed with 25RS-(hydroxyphenyl)-25-methoxy-2-methylidene-19,26,27-trinor-1-hydroxyvitamin D3

Structural highlights

5xpn is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[VDR_RAT] 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.^[1]

Publication Abstract from PubMed

Vitamin D receptor (VDR) antagonists can be classified into two categories: the first category of VDR antagonists, which do not stabilize the helix 11-12, and the second category of antagonists, which destabilize the helix 6-7 region. To elucidate the mechanism underlying the first category antagonists by using the crystal structure, we designed and synthesized several VDR ligands with a p-hydroxyphenyl group at the C25-position. Of these, 22S-butyl-25-carbonyl analogue 5b and 25-di-p-hydoroxyphenyl analogues 6a,b showed strong antagonistic activity. We succeeded in cocrystallizing the ligand-binding domain of VDR complexed with 5b and found that the structure showed an alternative conformation of the helix 11-12 that explained the mechanism of the first category antagonists. Taking the present and previous studies together, we could elucidate the mechanisms underlying first and second categories antagonists based on individual crystal structures. This study provides significant insights into antagonism against not only VDR but also nuclear receptors.

Vitamin D Analogues with a p-Hydroxyphenyl Group at the C25 Position: Crystal Structure of Vitamin D Receptor Ligand-Binding Domain Complexed with the Ligand Explains the Mechanism Underlying Full Antagonistic Action.,Kato A, Yamao M, Hashihara Y, Ishida H, Itoh T, Yamamoto K J Med Chem. 2017 Oct 26;60(20):8394-8406. doi: 10.1021/acs.jmedchem.7b00819. Epub, 2017 Oct 10. PMID:28954197^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vanhooke JL, Tadi BP, Benning MM, Plum LA, DeLuca HF. New analogs of 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 with conformationally restricted side chains: evaluation of biological activity and structural determination of VDR-bound conformations. Arch Biochem Biophys. 2007 Apr 15;460(2):161-5. Epub 2006 Dec 12. PMID:17227670 doi:10.1016/j.abb.2006.11.029
↑ Kato A, Yamao M, Hashihara Y, Ishida H, Itoh T, Yamamoto K. Vitamin D Analogues with a p-Hydroxyphenyl Group at the C25 Position: Crystal Structure of Vitamin D Receptor Ligand-Binding Domain Complexed with the Ligand Explains the Mechanism Underlying Full Antagonistic Action. J Med Chem. 2017 Oct 26;60(20):8394-8406. doi: 10.1021/acs.jmedchem.7b00819. Epub, 2017 Oct 10. PMID:28954197 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b00819

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xpn"

@@ Line 1: / Line 1: @@
 ==Crystal structure of VDR-LBD complexed with 25RS-(hydroxyphenyl)-25-methoxy-2-methylidene-19,26,27-trinor-1-hydroxyvitamin D3==
-<StructureSection load='5xpn' size='340' side='right' caption='[[5xpn]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
+<StructureSection load='5xpn' size='340' side='right'caption='[[5xpn]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xpn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XPN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XPN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xpn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XPN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XPN FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8BO:(1~{R},3~{R})-5-[(2~{E})-2-[(1~{R},3~{a}~{S},7~{a}~{R})-1-[(2~{R},6~{S})-6-(4-hydroxyphenyl)-6-methoxy-hexan-2-yl]-7~{a}-methyl-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-4-ylidene]ethylidene]-2-methylidene-cyclohexane-1,3-diol'>8BO</scene>, <scene name='pdbligand=9RO:(1~{R},3~{R})-5-[(2~{E})-2-[(1~{R},3~{a}~{S},7~{a}~{R})-1-[(2~{R},6~{R})-6-(4-hydroxyphenyl)-6-methoxy-hexan-2-yl]-7~{a}-methyl-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-4-ylidene]ethylidene]-2-methylidene-cyclohexane-1,3-diol'>9RO</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8BO:(1~{R},3~{R})-5-[(2~{E})-2-[(1~{R},3~{a}~{S},7~{a}~{R})-1-[(2~{R},6~{S})-6-(4-hydroxyphenyl)-6-methoxy-hexan-2-yl]-7~{a}-methyl-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-4-ylidene]ethylidene]-2-methylidene-cyclohexane-1,3-diol'>8BO</scene>, <scene name='pdbligand=9RO:(1~{R},3~{R})-5-[(2~{E})-2-[(1~{R},3~{a}~{S},7~{a}~{R})-1-[(2~{R},6~{R})-6-(4-hydroxyphenyl)-6-methoxy-hexan-2-yl]-7~{a}-methyl-2,3,3~{a},5,6,7-hexahydro-1~{H}-inden-4-ylidene]ethylidene]-2-methylidene-cyclohexane-1,3-diol'>9RO</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xpn OCA], [http://pdbe.org/5xpn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xpn RCSB], [http://www.ebi.ac.uk/pdbsum/5xpn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xpn ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5xpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xpn OCA], [http://pdbe.org/5xpn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xpn RCSB], [http://www.ebi.ac.uk/pdbsum/5xpn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xpn ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 5xpn" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Itoh, T]]
 [[Category: Kato, A]]

5xpn

From Proteopedia

Revision as of 06:56, 14 October 2020

Crystal structure of VDR-LBD complexed with 25RS-(hydroxyphenyl)-25-methoxy-2-methylidene-19,26,27-trinor-1-hydroxyvitamin D3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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