5yp6
RORgamma (263-509) complexed with SRC2 and Compound 6RORgamma (263-509) complexed with SRC2 and Compound 6
Structural highlights
FunctionRORG_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 PubMedBiaryl amides as new RORgammat modulators were discovered. The crystal structure of biaryl amide agonist 6 in complex with RORgammat ligand binding domain (LBD) was resolved, and both "short" and "long" inverse agonists were obtained by removing from 6 or adding to 6 a proper structural moiety. While "short" inverse agonist (8) recruits a corepressor peptide and dispels a coactivator peptide, "long" inverse agonist (9) dispels both. The two types of inverse agonists can be utilized as potential tools to study mechanisms of Th17 transcriptional network inhibition and related disease biology. From RORgammat Agonist to Two Types of RORgammat Inverse Agonists.,Wang Y, Cai W, Tang T, Liu Q, Yang T, Yang L, Ma Y, Zhang G, Huang Y, Song X, Orband-Miller LA, Wu Q, Zhou L, Xiang Z, Xiang JN, Leung S, Shao L, Lin X, Lobera M, Ren F ACS Med Chem Lett. 2018 Jan 22;9(2):120-124. doi: 10.1021/acsmedchemlett.7b00476., eCollection 2018 Feb 8. PMID:29456799[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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