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6a22

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Revision as of 21:25, 28 October 2020

Ternary complex of Human ROR gamma Ligand Binding Domain With Compound T.

Structural highlights

6a22 is a 8 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

[RORG_HUMAN] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. [NCOR2_HUMAN] Transcriptional corepressor of NR4A2/NURR1 and acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state (By similarity). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors.

Publication Abstract from PubMed

Retinoic acid-related orphan receptor gamma (RORgamma) plays pivotal roles in autoimmune diseases by controlling the lineage of interleukin 17 (IL-17)-producing CD4(+) T cells (Th17 cells). Structure-based drug design has proven fruitful in the development of inhibitors targeting the ligand binding domain (LBD) of RORgamma. Here, we present the crystal structure of a novel RORgamma inhibitor co-complex, in the presence of a corepressor (CoR) peptide. This ternary complex with compound T reveals the structural basis for an inhibitory mechanism different from the previously reported inverse agonist. Compared to the inverse agonist, compound T induces about 2 A shift of helix 5 (H5) backbone and side-chain conformational changes of Met365 on H5. These conformational changes correlate to reduced CoR peptide binding to RORgamma-LBD in the presence of compound T, which suggests that the shift of H5 is responsible. This crystal structure analysis will provide useful information for the development of novel and efficacious drugs for autoimmune disorders.

Ternary crystal structure of human RORgamma ligand-binding-domain, an inhibitor and corepressor peptide provides a new insight into corepressor interaction.,Noguchi M, Nomura A, Doi S, Yamaguchi K, Hirata K, Shiozaki M, Maeda K, Hirashima S, Kotoku M, Yamaguchi T, Katsuda Y, Crowe P, Tao H, Thacher S, Adachi T Sci Rep. 2018 Nov 26;8(1):17374. doi: 10.1038/s41598-018-35783-9. PMID:30478402^[1]

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

References

↑ Noguchi M, Nomura A, Doi S, Yamaguchi K, Hirata K, Shiozaki M, Maeda K, Hirashima S, Kotoku M, Yamaguchi T, Katsuda Y, Crowe P, Tao H, Thacher S, Adachi T. Ternary crystal structure of human RORgamma ligand-binding-domain, an inhibitor and corepressor peptide provides a new insight into corepressor interaction. Sci Rep. 2018 Nov 26;8(1):17374. doi: 10.1038/s41598-018-35783-9. PMID:30478402 doi:http://dx.doi.org/10.1038/s41598-018-35783-9

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/6a22"

@@ Line 1: / Line 1: @@
 ==Ternary complex of Human ROR gamma Ligand Binding Domain With Compound T.==
-<StructureSection load='6a22' size='340' side='right' caption='[[6a22]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
+<StructureSection load='6a22' size='340' side='right'caption='[[6a22]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6a22]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A22 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6a22]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A22 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6A22 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9P6:2-[2-[1-~{tert}-butyl-5-(4-methoxyphenyl)pyrazol-4-yl]-1,3-thiazol-4-yl]-~{N}-(oxan-4-ylmethyl)ethanamide'>9P6</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9P6:2-[2-[1-~{tert}-butyl-5-(4-methoxyphenyl)pyrazol-4-yl]-1,3-thiazol-4-yl]-~{N}-(oxan-4-ylmethyl)ethanamide'>9P6</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=6a22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a22 OCA], [http://pdbe.org/6a22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a22 RCSB], [http://www.ebi.ac.uk/pdbsum/6a22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a22 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=6a22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a22 OCA], [http://pdbe.org/6a22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a22 RCSB], [http://www.ebi.ac.uk/pdbsum/6a22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a22 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 6a22" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Nuclear receptor corepressor|Nuclear receptor corepressor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Adachi, T]]
 [[Category: Doi, S]]

6a22

From Proteopedia

Revision as of 21:25, 28 October 2020

Ternary complex of Human ROR gamma Ligand Binding Domain With Compound T.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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