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2zxm

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Revision as of 07:33, 18 October 2018

A New Class of Vitamin D Receptor Ligands that Induce Structural Rearrangement of the Ligand-binding Pocket

Structural highlights

2zxm is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2zxn
Gene:	Nr1i1, Vdr (Buffalo rat)
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] [MED1_XENTR] 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 (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

To identify novel vitamin D receptor (VDR) ligands that induce a novel architecture within the ligand-binding pocket (LBP), we have investigated eight 22-butyl-1alpha,24-dihydroxyvitamin D(3) derivatives (3-10), all having a butyl group as the branched alkyl side chain. We found that the 22S-butyl-20-epi-25,26,27-trinorvitamin D derivative 5 was a potent VDR agonist, whereas the corresponding compound 4 with the natural configuration at C(20) was a potent VDR antagonist. Analogues with the full vitamin D(3) side chain were less potent agonist, and whether they were agonists or antagonists depended on the 24-configuration. X-ray crystal structures demonstrated that the VDR-LBD accommodating the potent agonist 5 has an architecture wherein the lower side and the helix 11 side of the LBP is simply expanded relative to the canonical active-VDR situation; in contrast, the potent antagonist 4 induces an extra cavity to accommodate the branched moiety. This is the first report of a VDR antagonist that generates a new cavity to alter the canonical pocket structure of the ligand occupied VDR.

A New Class of Vitamin D Analogues that Induce Structural Rearrangement of the Ligand-Binding Pocket of the Receptor.,Inaba Y, Yoshimoto N, Sakamaki Y, Nakabayashi M, Ikura T, Tamamura H, Ito N, Shimizu M, Yamamoto K J Med Chem. 2009 Feb 4. PMID:19193059^[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
↑ Inaba Y, Yoshimoto N, Sakamaki Y, Nakabayashi M, Ikura T, Tamamura H, Ito N, Shimizu M, Yamamoto K. A New Class of Vitamin D Analogues that Induce Structural Rearrangement of the Ligand-Binding Pocket of the Receptor. J Med Chem. 2009 Feb 4. PMID:19193059 doi:10.1021/jm8014348

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2zxm"

@@ Line 1: / Line 1: @@
 ==A New Class of Vitamin D Receptor Ligands that Induce Structural Rearrangement of the Ligand-binding Pocket==
 <StructureSection load='2zxm' size='340' side='right' caption='[[2zxm]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zxn|2zxn]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nr1i1, Vdr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=2zxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zxm OCA], [http://pdbe.org/2zxm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zxm RCSB], [http://www.ebi.ac.uk/pdbsum/2zxm PDBsum]</span></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=2zxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zxm OCA], [http://pdbe.org/2zxm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zxm RCSB], [http://www.ebi.ac.uk/pdbsum/2zxm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zxm ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/2zxm_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/2zxm_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 50: / Line 51: @@
 [[Category: Transcription]]
 [[Category: Transcription regulation]]
+[[Category: Zinc]]
 [[Category: Zinc-finger]]

2zxm

From Proteopedia

Revision as of 07:33, 18 October 2018

A New Class of Vitamin D Receptor Ligands that Induce Structural Rearrangement of the Ligand-binding Pocket

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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