1exa

From Proteopedia

(Difference between revisions)

Current revision

ENANTIOMER DISCRIMINATION ILLUSTRATED BY CRYSTAL STRUCTURES OF THE HUMAN RETINOIC ACID RECEPTOR HRARGAMMA LIGAND BINDING DOMAIN: THE COMPLEX WITH THE ACTIVE R-ENANTIOMER BMS270394.

Structural highlights

1exa is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.59Å
Ligands:	,
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) is a member of the nuclear receptor superfamily that regulates the transcription of target genes in a ligand-dependent manner. The three hRAR isotypes are targets for retinoids that are used in the treatment of various diseases, including breast cancer and skin diseases. Drug efficiency and safety depend on the pharmacological activity of enantiomers, which can differ because of the chiral environment generated by the target. We report the crystal structures of the hRARgamma ligand-binding domain bound to two enantiomers, the active BMS270394 and the inactive BMS270395, solved at 1.6 A and 1.7 A resolution, respectively. The crystal structures reveal that in both enantiomers, the hydroxyl moiety attached to the chiral center forms a hydrogen bond to the Met-272 sulfur atom, thus imposing a conformation of BMS270395 that differs significantly from that observed for BMS270394 and other known retinoids. BMS270395 adopts an energetically unfavorable conformation, accounting for its inactivity; in contrast, the conformation of BMS270394 is close to an energy minimum. Our high-resolution data allow rationalization of enantiomer discrimination by the receptor and provide a model system for the pharmacological properties of enantiomeric pairs.

Enantiomer discrimination illustrated by high-resolution crystal structures of the human nuclear receptor hRARgamma.,Klaholz BP, Mitschler A, Belema M, Zusi C, Moras D Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6322-7. PMID:10841540^[1]

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

References

↑ Klaholz BP, Mitschler A, Belema M, Zusi C, Moras D. Enantiomer discrimination illustrated by high-resolution crystal structures of the human nuclear receptor hRARgamma. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6322-7. PMID:10841540

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/1exa"

@@ Line 3: / Line 3: @@
 <StructureSection load='1exa' size='340' side='right'caption='[[1exa]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1exa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EXA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1exa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EXA FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=394:R-3-FLUORO-4-[2-HYDROXY-2-(5,5,8,8-TETRAMETHYL-5,6,7,8,-TETRAHYDRO-NAPHTALEN-2-YL)-ACETYLAMINO]-BENZOIC+ACID'>394</scene>, <scene name='pdbligand=LMU:DODECYL-ALPHA-D-MALTOSIDE'>LMU</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1exx|1exx]], [[2lbd|2lbd]], [[3lbd|3lbd]], [[4lbd|4lbd]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=394:R-3-FLUORO-4-[2-HYDROXY-2-(5,5,8,8-TETRAMETHYL-5,6,7,8,-TETRAHYDRO-NAPHTALEN-2-YL)-ACETYLAMINO]-BENZOIC+ACID'>394</scene>, <scene name='pdbligand=LMU:DODECYL-ALPHA-D-MALTOSIDE'>LMU</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1exa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1exa OCA], [https://pdbe.org/1exa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1exa RCSB], [https://www.ebi.ac.uk/pdbsum/1exa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1exa ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/RARG_HUMAN 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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 34: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Belema, M]]
+[[Category: Belema M]]
-[[Category: Klaholz, B P]]
+[[Category: Klaholz BP]]
-[[Category: Mitschler, A]]
+[[Category: Mitschler A]]
-[[Category: Moras, D]]
+[[Category: Moras D]]
-[[Category: SPINE, Structural Proteomics in Europe]]
+[[Category: Zusi C]]
-[[Category: Zusi, C]]
-[[Category: Antiparallel alpha-helical sandwich fold]]
-[[Category: Enantiomer discrimination]]
-[[Category: Gene regulation]]
-[[Category: Retinoid ligand complex]]
-[[Category: Spine]]
-[[Category: Structural genomic]]
-[[Category: Structural proteomics in europe]]

1exa

From Proteopedia

Current revision

ENANTIOMER DISCRIMINATION ILLUSTRATED BY CRYSTAL STRUCTURES OF THE HUMAN RETINOIC ACID RECEPTOR HRARGAMMA LIGAND BINDING DOMAIN: THE COMPLEX WITH THE ACTIVE R-ENANTIOMER BMS270394.

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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