4NB6

Crystal structure of the ligand binding domain of RORC with T0901317

4NB6 の概要

• エントリーDOI: 10.2210/pdb4nb6/pdb
• 関連するPDBエントリー: 1PQ9 1PQC 2O91
• 分子名称: Nuclear receptor ROR-gamma, N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE (3 entities in total)
• 機能のキーワード: alpha-helical, transcription factor, nucleus, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (Probable): P51449
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59045.75

構造登録者

Hymowitz, S.G.,Boenig-de Leon, G. (登録日: 2013-10-22, 公開日: 2013-11-27, 最終更新日: 2023-09-20)

主引用文献

Fauber, B.P.,de Leon Boenig, G.,Burton, B.,Eidenschenk, C.,Everett, C.,Gobbi, A.,Hymowitz, S.G.,Johnson, A.R.,Liimatta, M.,Lockey, P.,Norman, M.,Ouyang, W.,Rene, O.,Wong, H.
Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc.
Bioorg.Med.Chem.Lett., 23:6604-6609, 2013

PubMed Abstract: The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors.

PubMed: 24239186
DOI: 10.1016/j.bmcl.2013.10.054

実験手法

X-RAY DIFFRACTION (2.85 Å)