8fb2

From Proteopedia

(Difference between revisions)

Current revision

HUMAN RETENOID-RELATED ORPHAN RECEPTOR-GAMMA (RORC2) LIGAND-BINDING DOMAIN IN COMPLEX WITH COMPOUND 8 ANDINDAZOLE ACID BOUND IN H12-POCKET

Structural highlights

8fb2 is a 2 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 2.3Å
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.

Publication Abstract from PubMed

Macrocyclic retinoic acid receptor-related orphan receptor C2 (RORC2) inverse agonists have been designed with favorable properties for topical administration. Inspired by the unanticipated bound conformation of an acyclic sulfonamide-based RORC2 ligand from cocrystal structure analysis, macrocyclic linker connections between the halves of the molecule were explored. Further optimization of analogues was accomplished to maximize potency and refine physiochemical properties (MW, lipophilicity) best suited for topical application. Compound 14 demonstrated potent inhibition of interleukin-17A (IL-17A) production by human Th17 cells and in vitro permeation through healthy human skin achieving high total compound concentration in both skin epidermis and dermis layers.

Macrocyclic Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonists.,Schnute ME, Trujillo JI, Lee KL, Unwalla R, Vajdos FF, Kauppi B, Nuhant P, Flick AC, Crouse KK, Zhao Y, Samuel A, Lombardo V, Taylor AP, Brault AL, Knafels JD, Vazquez ML, Berstein G ACS Med Chem Lett. 2023 Jan 18;14(2):191-198. doi: , 10.1021/acsmedchemlett.2c00500. eCollection 2023 Feb 9. PMID:36793423^[1]

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

References

↑ Schnute ME, Trujillo JI, Lee KL, Unwalla R, Vajdos FF, Kauppi B, Nuhant P, Flick AC, Crouse KK, Zhao Y, Samuel A, Lombardo V, Taylor AP, Brault AL, Knafels JD, Vazquez ML, Berstein G. Macrocyclic Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonists. ACS Med Chem Lett. 2023 Jan 18;14(2):191-198. PMID:36793423 doi:10.1021/acsmedchemlett.2c00500

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/8fb2"

Categories: Homo sapiens | Large Structures | Vajdos FF

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8fb2 is ON HOLD
+==HUMAN RETENOID-RELATED ORPHAN RECEPTOR-GAMMA (RORC2) LIGAND-BINDING DOMAIN IN COMPLEX WITH COMPOUND 8 ANDINDAZOLE ACID BOUND IN H12-POCKET==
+<StructureSection load='8fb2' size='340' side='right'caption='[[8fb2]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8fb2]] is a 2 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=8FB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FB2 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XNX:4-[1-[2,6-bis(chloranyl)phenyl]carbonyl-4-fluoranyl-indazol-3-yl]benzoic+acid'>XNX</scene>, <scene name='pdbligand=XO5:(1R,15S)-16-(cyclopropylacetyl)-5-fluoro-20-methyl-9lambda~6~-thia-1,8,16-triazatricyclo[13.3.1.1~3,7~]icosa-3(20),4,6-triene-9,9-dione'>XO5</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=8fb2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fb2 OCA], [https://pdbe.org/8fb2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fb2 RCSB], [https://www.ebi.ac.uk/pdbsum/8fb2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fb2 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/RORG_HUMAN 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Macrocyclic retinoic acid receptor-related orphan receptor C2 (RORC2) inverse agonists have been designed with favorable properties for topical administration. Inspired by the unanticipated bound conformation of an acyclic sulfonamide-based RORC2 ligand from cocrystal structure analysis, macrocyclic linker connections between the halves of the molecule were explored. Further optimization of analogues was accomplished to maximize potency and refine physiochemical properties (MW, lipophilicity) best suited for topical application. Compound 14 demonstrated potent inhibition of interleukin-17A (IL-17A) production by human Th17 cells and in vitro permeation through healthy human skin achieving high total compound concentration in both skin epidermis and dermis layers.
-Authors: Vajdos, F.F.
+Macrocyclic Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonists.,Schnute ME, Trujillo JI, Lee KL, Unwalla R, Vajdos FF, Kauppi B, Nuhant P, Flick AC, Crouse KK, Zhao Y, Samuel A, Lombardo V, Taylor AP, Brault AL, Knafels JD, Vazquez ML, Berstein G ACS Med Chem Lett. 2023 Jan 18;14(2):191-198. doi: , 10.1021/acsmedchemlett.2c00500. eCollection 2023 Feb 9. PMID:36793423<ref>PMID:36793423</ref>
-Description: HUMAN RETENOID-RELATED ORPHAN RECEPTOR-GAMMA (RORC2) LIGAND-BINDING DOMAIN IN COMPLEX WITH COMPOUND 8 ANDINDAZOLE ACID BOUND IN H12-POCKET
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Vajdos, F.F]]
+<div class="pdbe-citations 8fb2" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Vajdos FF]]

8fb2

From Proteopedia

Current revision

HUMAN RETENOID-RELATED ORPHAN RECEPTOR-GAMMA (RORC2) LIGAND-BINDING DOMAIN IN COMPLEX WITH COMPOUND 8 ANDINDAZOLE ACID BOUND IN H12-POCKET

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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