5ayg

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of the Human ROR gamma Ligand Binding Domain With 3g

Structural highlights

5ayg 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 2.6Å
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

A novel series of RORgamma inhibitors was identified starting with the HTS hit 1. After SAR investigation based on a prospective consideration of two drug-likeness metrics, ligand efficiency (LE) and fraction of sp(3) carbon atoms (Fsp(3)), significant improvement of metabolic stability as well as reduction of CYP inhibition was observed, which finally led to discovery of a selective and orally efficacious RORgamma inhibitor 3z.

SAR Exploration Guided by LE and Fsp(3): Discovery of a Selective and Orally Efficacious RORgamma Inhibitor.,Hirata K, Kotoku M, Seki N, Maeba T, Maeda K, Hirashima S, Sakai T, Obika S, Hori A, Hase Y, Yamaguchi T, Katsuda Y, Hata T, Miyagawa N, Arita K, Nomura Y, Asahina K, Aratsu Y, Kamada M, Adachi T, Noguchi M, Doi S, Crowe P, Bradley E, Steensma R, Tao H, Fenn M, Babine R, Li X, Thacher S, Hashimoto H, Shiozaki M ACS Med Chem Lett. 2015 Nov 4;7(1):23-7. doi: 10.1021/acsmedchemlett.5b00253., eCollection 2016 Jan 14. PMID:26819660^[1]

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

References

↑ Hirata K, Kotoku M, Seki N, Maeba T, Maeda K, Hirashima S, Sakai T, Obika S, Hori A, Hase Y, Yamaguchi T, Katsuda Y, Hata T, Miyagawa N, Arita K, Nomura Y, Asahina K, Aratsu Y, Kamada M, Adachi T, Noguchi M, Doi S, Crowe P, Bradley E, Steensma R, Tao H, Fenn M, Babine R, Li X, Thacher S, Hashimoto H, Shiozaki M. SAR Exploration Guided by LE and Fsp(3): Discovery of a Selective and Orally Efficacious RORgamma Inhibitor. ACS Med Chem Lett. 2015 Nov 4;7(1):23-7. doi: 10.1021/acsmedchemlett.5b00253., eCollection 2016 Jan 14. PMID:26819660 doi:http://dx.doi.org/10.1021/acsmedchemlett.5b00253

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/5ayg"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5ayg]] 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=5AYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AYG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4LQ:3-[5-(2-CYCLOHEXYLETHYL)-4-ETHYL-1,2,4-TRIAZOL-3-YL]-N-NAPHTHALEN-1-YL-PROPANAMIDE'>4LQ</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]] 2.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4LQ:3-[5-(2-CYCLOHEXYLETHYL)-4-ETHYL-1,2,4-TRIAZOL-3-YL]-N-NAPHTHALEN-1-YL-PROPANAMIDE'>4LQ</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=5ayg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ayg OCA], [https://pdbe.org/5ayg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ayg RCSB], [https://www.ebi.ac.uk/pdbsum/5ayg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ayg ProSAT]</span></td></tr>
 </table>

5ayg

From Proteopedia

Current revision

Crystal Structure of the Human ROR gamma Ligand Binding Domain With 3g

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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