5w4r

From Proteopedia

(Difference between revisions)

Revision as of 08:48, 30 September 2020

Structure of RORgt bound to a tertiary alcohol

Structural highlights

5w4r is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5w4v
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.

Publication Abstract from PubMed

We identified 6-substituted quinolines as modulators of the retinoic acid receptor-related orphan receptor gamma t (RORgammat). The synthesis of this class of RORgammat modulators is reported, and optimization of the substituents at the quinoline 6-position that produced compounds with high affinity for the receptor is detailed. This effort identified molecules that act as potent, full inverse agonists in a RORgammat-driven cell-based reporter assay. The X-ray crystal structures of two full inverse agonists from this chemical series bound to the RORgammat ligand binding domain are disclosed, and we highlight the interaction of a hydrogen-bond acceptor on the 6-position substituent of the inverse agonist with Glu379:NH as a conserved binding contact.

6-Substituted quinolines as RORgammat inverse agonists.,Barbay JK, Cummings MD, Abad M, Castro G, Kreutter KD, Kummer DA, Maharoof U, Milligan C, Nishimura R, Pierce J, Schalk-Hihi C, Spurlino J, Tanis VM, Urbanski M, Venkatesan H, Wang A, Woods C, Wolin R, Xue X, Edwards JP, Fourie AM, Leonard K Bioorg Med Chem Lett. 2017 Dec 1;27(23):5277-5283. doi:, 10.1016/j.bmcl.2017.10.027. Epub 2017 Oct 16. PMID:29079472^[1]

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

References

↑ Barbay JK, Cummings MD, Abad M, Castro G, Kreutter KD, Kummer DA, Maharoof U, Milligan C, Nishimura R, Pierce J, Schalk-Hihi C, Spurlino J, Tanis VM, Urbanski M, Venkatesan H, Wang A, Woods C, Wolin R, Xue X, Edwards JP, Fourie AM, Leonard K. 6-Substituted quinolines as RORgammat inverse agonists. Bioorg Med Chem Lett. 2017 Dec 1;27(23):5277-5283. doi:, 10.1016/j.bmcl.2017.10.027. Epub 2017 Oct 16. PMID:29079472 doi:http://dx.doi.org/10.1016/j.bmcl.2017.10.027

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5w4r"

Categories: Large Structures | Spurlino, J | Nuclear protein | Rorgt nuclear hormone receptor

@@ Line 1: / Line 1: @@
 ==Structure of RORgt bound to a tertiary alcohol==
-<StructureSection load='5w4r' size='340' side='right' caption='[[5w4r]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+<StructureSection load='5w4r' size='340' side='right'caption='[[5w4r]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5w4r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W4R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W4R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5w4r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W4R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5W4R FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9WD:1-{4-[(R)-(4-chloro-2-methoxy-3-{[4-(1H-pyrazol-1-yl)phenyl]methyl}quinolin-6-yl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl]piperidin-1-yl}ethan-1-one'>9WD</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9WD:1-{4-[(R)-(4-chloro-2-methoxy-3-{[4-(1H-pyrazol-1-yl)phenyl]methyl}quinolin-6-yl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl]piperidin-1-yl}ethan-1-one'>9WD</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5w4v|5w4v]]</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=5w4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w4r OCA], [http://pdbe.org/5w4r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w4r RCSB], [http://www.ebi.ac.uk/pdbsum/5w4r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w4r 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=5w4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w4r OCA], [http://pdbe.org/5w4r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w4r RCSB], [http://www.ebi.ac.uk/pdbsum/5w4r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w4r ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Spurlino, J]]
 [[Category: Nuclear protein]]
 [[Category: Rorgt nuclear hormone receptor]]

5w4r

From Proteopedia

Revision as of 08:48, 30 September 2020

Structure of RORgt bound to a tertiary alcohol

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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