6D27

Crystal structure of the prostaglandin D2 receptor CRTH2 with CAY10471

6D27 の概要

• エントリーDOI: 10.2210/pdb6d27/pdb
• 関連するPDBエントリー: 6D26
• 分子名称: Prostaglandin D2 receptor 2, Endolysin chimera, SULFATE ION, [(3R)-3-{[(4-fluorophenyl)sulfonyl](methyl)amino}-1,2,3,4-tetrahydro-9H-carbazol-9-yl]acetic acid, ... (9 entities in total)
• 機能のキーワード: gpcr, membrane protein-antagonist complex, membrane protein/antagonist
• 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: 54788.63

構造登録者

Wang, L.,Yao, D.,Deepak, K.,Liu, H.,Gong, W.,Fan, H.,Wei, Z.,Zhang, C. (登録日: 2018-04-13, 公開日: 2018-10-03, 最終更新日: 2023-10-04)

主引用文献

Wang, L.,Yao, D.,Deepak, R.N.V.K.,Liu, H.,Xiao, Q.,Fan, H.,Gong, W.,Wei, Z.,Zhang, C.
Structures of the Human PGD2Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition.
Mol. Cell, 72:48-59.e4, 2018

PubMed Abstract: The signaling of prostaglandin D (PGD) through G-protein-coupled receptor (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence suggests the therapeutic benefits of blocking CRTH2 signaling in many inflammatory disorders. Currently, a number of CRTH2 antagonists are under clinical investigation, and one compound, fevipiprant, has advanced to phase 3 clinical trials for asthma. Here, we present the crystal structures of human CRTH2 with two antagonists, fevipiprant and CAY10471. The structures, together with docking and ligand-binding data, reveal a semi-occluded pocket covered by a well-structured amino terminus and different binding modes of chemically diverse CRTH2 antagonists. Structural analysis suggests a ligand entry port and a binding process that is facilitated by opposite charge attraction for PGD, which differs significantly from the binding pose and binding environment of lysophospholipids and endocannabinoids, revealing a new mechanism for lipid recognition by GPCRs.

PubMed: 30220562
DOI: 10.1016/j.molcel.2018.08.009

実験手法

X-RAY DIFFRACTION (2.738 Å)