1fcy

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(Difference between revisions)

Revision as of 10:54, 13 September 2017

ISOTYPE SELECTIVITY OF THE HUMAN RETINOIC ACID NUCLEAR RECEPTOR HRAR: THE COMPLEX WITH THE RARBETA/GAMMA-SELECTIVE RETINOID CD564

Structural highlights

1fcy is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2lbd, 3lbd, 1exa, 1exx, 1fcz, 1fcx, 1fd0
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RARG_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (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 human retinoic acid receptor (hRAR) belongs to the family of nuclear receptors that regulate transcription in a ligand-dependent way. The isotypes RARalpha,beta and gamma are distinct pharmacological targets for retinoids that are involved in the treatment of various skin diseases and cancers, in particular breast cancer and acute promyelocytic leukemia. Therefore, synthetic retinoids have been developed aiming at isotype selectivity and reduced side-effects. We report the crystal structures of three complexes of the hRARgamma ligand-binding domain (LBD) bound to agonist retinoids that possess selectivity either for RARgamma (BMS184394) or for RARbeta/gamma (CD564), or that are potent for all RAR-isotypes (panagonist BMS181156). The high resolution data (1.3-1. 5 A) provide a description at the atomic level of the ligand pocket revealing the molecular determinants for the different degrees of ligand selectivity. The comparison of the complexes of the chemically closely related retinoids BMS184394 and CD564 shows that the side-chain of Met272 adopts different conformations depending on the presence of a hydrogen bond between its sulfur atom and the ligand. This accounts for their different isotype selectivity. On the other hand, the difference between the pan- and the RARbeta, gamma-selective agonist is probably due to a steric discrimination at the level of the 2-naphthoic acid moiety of CD564. Based on this study, we propose a model for a complex with the RARgamma-specific agonist CD666 that shows the possible applications for structure-based drug design of RAR isotype-selective retinoids.

Structural basis for isotype selectivity of the human retinoic acid nuclear receptor.,Klaholz BP, Mitschler A, Moras D J Mol Biol. 2000 Sep 8;302(1):155-70. PMID:10964567^[1]

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

References

↑ Klaholz BP, Mitschler A, Moras D. Structural basis for isotype selectivity of the human retinoic acid nuclear receptor. J Mol Biol. 2000 Sep 8;302(1):155-70. PMID:10964567 doi:10.1006/jmbi.2000.4032

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/1fcy"

@@ Line 1: / Line 1: @@
 ==ISOTYPE SELECTIVITY OF THE HUMAN RETINOIC ACID NUCLEAR RECEPTOR HRAR: THE COMPLEX WITH THE RARBETA/GAMMA-SELECTIVE RETINOID CD564==
 <StructureSection load='1fcy' size='340' side='right' caption='[[1fcy]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1fcy]] 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=1FCY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FCY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1fcy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FCY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FCY FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=564:6-(5,5,8,8-TETRAMETHYL-5,6,7,8-TETRAHYDRO-NAPHTALENE-2-CARBONYL)-NAPHTALENE-2-CARBOXYLIC+ACID'>564</scene>, <scene name='pdbligand=LMU:DODECYL-ALPHA-D-MALTOSIDE'>LMU</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lbd|2lbd]], [[3lbd|3lbd]], [[1exa|1exa]], [[1exx|1exx]], [[1fcz|1fcz]], [[1fcx|1fcx]], [[1fd0|1fd0]]</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=1fcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fcy OCA], [http://pdbe.org/1fcy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fcy RCSB], [http://www.ebi.ac.uk/pdbsum/1fcy 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=1fcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fcy OCA], [http://pdbe.org/1fcy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fcy RCSB], [http://www.ebi.ac.uk/pdbsum/1fcy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fcy ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
     <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=1fcy ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 35: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
 [[Category: Klaholz, B P]]
 [[Category: Mitschler, A]]

1fcy

From Proteopedia

Revision as of 10:54, 13 September 2017

ISOTYPE SELECTIVITY OF THE HUMAN RETINOIC ACID NUCLEAR RECEPTOR HRAR: THE COMPLEX WITH THE RARBETA/GAMMA-SELECTIVE RETINOID CD564

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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