6RZ5

XFEL crystal structure of the human cysteinyl leukotriene receptor 1 in complex with zafirlukast

6RZ5 の概要

• エントリーDOI: 10.2210/pdb6rz5/pdb
• 分子名称: Cysteinyl leukotriene receptor 1,Soluble cytochrome b562,Cysteinyl leukotriene receptor 1, zafirlukast, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (7 entities in total)
• 機能のキーワード: gpcr, lcp, membrane protein, cysteinyl leukotriene, ltd4, cyslt1, cysltr1, cyslt1r, asthma, zafirlukast, bril, sodium site, cysteinyl leukotriene receptor 1, xfel, serial femtosecond crystallography, sfx
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 109293.40

構造登録者

Luginina, A.,Gusach, A.,Marin, E.,Mishin, A.,Brouillette, R.,Popov, P.,Shiryaeva, A.,Besserer-Offroy, E.,Longpre, J.M.,Lyapina, E.,Ishchenko, A.,Patel, N.,Polovinkin, V.,Safronova, N.,Bogorodskiy, A.,Edelweiss, E.,Liu, W.,Batyuk, A.,Gordeliy, V.,Han, G.W.,Sarret, P.,Katritch, V.,Borshchevskiy, V.,Cherezov, V. (登録日: 2019-06-12, 公開日: 2019-10-30, 最終更新日: 2024-11-13)

主引用文献

Luginina, A.,Gusach, A.,Marin, E.,Mishin, A.,Brouillette, R.,Popov, P.,Shiriaeva, A.,Besserer-Offroy, E.,Longpre, J.M.,Lyapina, E.,Ishchenko, A.,Patel, N.,Polovinkin, V.,Safronova, N.,Bogorodskiy, A.,Edelweiss, E.,Hu, H.,Weierstall, U.,Liu, W.,Batyuk, A.,Gordeliy, V.,Han, G.W.,Sarret, P.,Katritch, V.,Borshchevskiy, V.,Cherezov, V.
Structure-based mechanism of cysteinyl leukotriene receptor inhibition by antiasthmatic drugs.
Sci Adv, 5:eaax2518-eaax2518, 2019

PubMed Abstract: The G protein-coupled cysteinyl leukotriene receptor CysLTR mediates inflammatory processes and plays a major role in numerous disorders, including asthma, allergic rhinitis, cardiovascular disease, and cancer. Selective CysLTR antagonists are widely prescribed as antiasthmatic drugs; however, these drugs demonstrate low effectiveness in some patients and exhibit a variety of side effects. To gain deeper understanding into the functional mechanisms of CysLTRs, we determined the crystal structures of CysLTR bound to two chemically distinct antagonists, zafirlukast and pranlukast. The structures reveal unique ligand-binding modes and signaling mechanisms, including lateral ligand access to the orthosteric pocket between transmembrane helices TM4 and TM5, an atypical pattern of microswitches, and a distinct four-residue-coordinated sodium site. These results provide important insights and structural templates for rational discovery of safer and more effective drugs.

PubMed: 31633023
DOI: 10.1126/sciadv.aax2518

実験手法

X-RAY DIFFRACTION (2.53 Å)