2zmj

From Proteopedia

(Difference between revisions)

Revision as of 23:20, 5 August 2016

Crystal Structure of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and/or Partial Agonism

Structural highlights

2zmj 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:	2zmh, 2zmi
Gene:	Vdr, Nr1i1 (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

The X-ray crystal structures of the rat VDR ligand-binding domain complexed with 19-norvitamin D compounds that contain an adamantyl substituent at the side-chain terminus, 2a (ADTT), 2b (ADNY), and 2c (ADMI4) and a coactivator peptide derived from DRIP205 are reported. These compounds show a series of partial agonistic (10-75% efficacy)/antagonistic activities. All of these complexed receptors are crystallized in the canonical active conformation, regardless of their activity profiles. The bulky adamantyl side chain does not crowd helix 12 but protrudes into the gap formed by helix 11, loop 11-12, helix 3, and loop 6-7, thereby widening the ligand binding pocket. We suggest that these structural changes destabilize the active protein conformation and reduce its contribution to equilibrium among the active and inactive conformations. The coactivator peptide traps the minor active conformation, and the equilibrium shifts to the active conformation. As a result, these ligands show partial agonistic activities.

Crystal Structures of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and Partial Agonism.,Nakabayashi M, Yamada S, Yoshimoto N, Tanaka T, Igarashi M, Ikura T, Ito N, Makishima M, Tokiwa H, Deluca HF, Shimizu M J Med Chem. 2008 Aug 19. PMID:18710208^[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
↑ Nakabayashi M, Yamada S, Yoshimoto N, Tanaka T, Igarashi M, Ikura T, Ito N, Makishima M, Tokiwa H, Deluca HF, Shimizu M. Crystal Structures of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and Partial Agonism. J Med Chem. 2008 Aug 19. PMID:18710208 doi:10.1021/jm8004477

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/2zmj"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and/or Partial Agonism==
 <StructureSection load='2zmj' size='340' side='right' caption='[[2zmj]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2zmj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZMJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2zmj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZMJ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MI4:(1R,3R,7E,17BETA)-17-{(1S,2E,5R)-5-HYDROXY-1-METHYL-6-[(3S,5S,7S)-TRICYCLO[3.3.1.1~3,7~]DEC-1-YL]HEX-2-EN-1-YL}-2-METHYLIDENE-9,10-SECOESTRA-5,7-DIENE-1,3-DIOL'>MI4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zmh|2zmh]], [[2zmi|2zmi]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Vdr, Nr1i1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Vdr, Nr1i1 ([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=2zmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zmj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zmj RCSB], [http://www.ebi.ac.uk/pdbsum/2zmj 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=2zmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zmj OCA], [http://pdbe.org/2zmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zmj RCSB], [http://www.ebi.ac.uk/pdbsum/2zmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zmj ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2zmj ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2zmj" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Rattus norvegicus]]
+[[Category: Buffalo rat]]
 [[Category: DeLuca, H F]]
 [[Category: Igarashi, M]]

2zmj

From Proteopedia

Revision as of 23:20, 5 August 2016

Crystal Structure of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and/or Partial Agonism

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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