6PS7

XFEL A2aR structure by ligand exchange from LUF5843 to ZM241385.

6PS7 の概要

• エントリーDOI: 10.2210/pdb6ps7/pdb
• 分子名称: Adenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a, 4-{2-[(7-amino-2-furan-2-yl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino]ethyl}phenol, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (8 entities in total)
• 機能のキーワード: gpcr, complex-lcp method, sbdd, drug design, xfel, lcp-sfx, ligand exchange, luf5843, zm241385, a2aar, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 58144.17

構造登録者

Ishchenko, A.,Stauch, B.,Han, G.W.,Batyuk, A.,Shiriaeva, A.,Li, C.,Zatsepin, N.A.,Weierstall, U.,Liu, W.,Nango, E.,Nakane, T.,Tanaka, R.,Tono, K.,Joti, Y.,Iwata, S.,Moraes, I.,Gati, C.,Cherezov, C. (登録日: 2019-07-12, 公開日: 2019-11-13, 最終更新日: 2024-11-06)

主引用文献

Ishchenko, A.,Stauch, B.,Han, G.W.,Batyuk, A.,Shiriaeva, A.,Li, C.,Zatsepin, N.,Weierstall, U.,Liu, W.,Nango, E.,Nakane, T.,Tanaka, R.,Tono, K.,Joti, Y.,Iwata, S.,Moraes, I.,Gati, C.,Cherezov, V.
Toward G protein-coupled receptor structure-based drug design using X-ray lasers.
Iucrj, 6:1106-1119, 2019

PubMed Abstract: Rational structure-based drug design (SBDD) relies on the availability of a large number of co-crystal structures to map the ligand-binding pocket of the target protein and use this information for lead-compound optimization via an iterative process. While SBDD has proven successful for many drug-discovery projects, its application to G protein-coupled receptors (GPCRs) has been limited owing to extreme difficulties with their crystallization. Here, a method is presented for the rapid determination of multiple co-crystal structures for a target GPCR in complex with various ligands, taking advantage of the serial femtosecond crystallography approach, which obviates the need for large crystals and requires only submilligram quantities of purified protein. The method was applied to the human β-adrenergic receptor, resulting in eight room-temperature co-crystal structures with six different ligands, including previously unreported structures with carvedilol and propranolol. The generality of the proposed method was tested with three other receptors. This approach has the potential to enable SBDD for GPCRs and other difficult-to-crystallize membrane proteins.

PubMed: 31709066
DOI: 10.1107/S2052252519013137

実験手法

X-RAY DIFFRACTION (1.85 Å)