5W4R

Structure of RORgt bound to a tertiary alcohol

5W4R の概要

• エントリーDOI: 10.2210/pdb5w4r/pdb
• 関連するPDBエントリー: 5W4V
• 分子名称: Nuclear receptor ROR-gamma, 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 (3 entities in total)
• 機能のキーワード: rorgt nuclear hormone receptor, nuclear protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : P51449
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51628.51

構造登録者

Spurlino, J. (登録日: 2017-06-12, 公開日: 2017-12-27, 最終更新日: 2024-03-13)

主引用文献

Barbay, J.K.,Cummings, M.D.,Abad, M.,Castro, G.,Kreutter, K.D.,Kummer, D.A.,Maharoof, U.,Milligan, C.,Nishimura, R.,Pierce, J.,Schalk-Hihi, C.,Spurlino, J.,Tanis, V.M.,Urbanski, M.,Venkatesan, H.,Wang, A.,Woods, C.,Wolin, R.,Xue, X.,Edwards, J.P.,Fourie, A.M.,Leonard, K.
6-Substituted quinolines as ROR gamma t inverse agonists.
Bioorg. Med. Chem. Lett., 27:5277-5283, 2017

PubMed Abstract: We identified 6-substituted quinolines as modulators of the retinoic acid receptor-related orphan receptor gamma t (RORγt). The synthesis of this class of RORγt 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 RORγt-driven cell-based reporter assay. The X-ray crystal structures of two full inverse agonists from this chemical series bound to the RORγt 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.

PubMed: 29079472
DOI: 10.1016/j.bmcl.2017.10.027

実験手法

X-RAY DIFFRACTION (3.002 Å)