4Z36

Crystal Structure of Human Lysophosphatidic Acid Receptor 1 in complex with ONO-3080573

4Z36 の概要

• エントリーDOI: 10.2210/pdb4z36/pdb
• 関連するPDBエントリー: 4Z34 4Z35
• 分子名称: Lysophosphatidic acid receptor 1,Soluble cytochrome b562, 1-(4-{[(2S,3R)-2-(2,3-dihydro-1H-inden-2-yloxy)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]oxy}phenyl)cyclopropan ecarboxylic acid, (2S)-2,3-dihydroxypropyl (7Z)-tetradec-7-enoate, ... (4 entities in total)
• 機能のキーワード: human lysophosphatidic acid receptor 1 (lpa1), g-protein coupled receptor (gpcr), membrane protein, antagonist, endogenous ligand, psi-biology, structural genomics, gpcr network, lipidic cubic phase (lcp), novel disulfide bond engineering, compound design, polypharmacology, lipid receptor, transport protein-inhibitor complex, transport protein/inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell surface : Q92633
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52661.36

構造登録者

Chrencik, J.E.,Roth, C.B.,Terakado, M.,Kurata, H.,Omi, R.,Kihara, Y.,Warshaviak, D.,Nakade, S.,Asmar-Rovira, G.,Mileni, M.,Mizuno, H.,Griffith, M.T.,Rodgers, C.,Han, G.W.,Velasquez, J.,Chun, J.,Stevens, R.C.,Hanson, M.A.,GPCR Network (GPCR) (登録日: 2015-03-30, 公開日: 2015-06-03, 最終更新日: 2024-11-13)

主引用文献

Chrencik, J.E.,Roth, C.B.,Terakado, M.,Kurata, H.,Omi, R.,Kihara, Y.,Warshaviak, D.,Nakade, S.,Asmar-Rovira, G.,Mileni, M.,Mizuno, H.,Griffith, M.T.,Rodgers, C.,Han, G.W.,Velasquez, J.,Chun, J.,Stevens, R.C.,Hanson, M.A.
Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1.
Cell, 161:1633-1643, 2015

PubMed Abstract: Lipid biology continues to emerge as an area of significant therapeutic interest, particularly as the result of an enhanced understanding of the wealth of signaling molecules with diverse physiological properties. This growth in knowledge is epitomized by lysophosphatidic acid (LPA), which functions through interactions with at least six cognate G protein-coupled receptors. Herein, we present three crystal structures of LPA1 in complex with antagonist tool compounds selected and designed through structural and stability analyses. Structural analysis combined with molecular dynamics identified a basis for ligand access to the LPA1 binding pocket from the extracellular space contrasting with the proposed access for the sphingosine 1-phosphate receptor. Characteristics of the LPA1 binding pocket raise the possibility of promiscuous ligand recognition of phosphorylated endocannabinoids. Cell-based assays confirmed this hypothesis, linking the distinct receptor systems through metabolically related ligands with potential functional and therapeutic implications for treatment of disease.

PubMed: 26091040
DOI: 10.1016/j.cell.2015.06.002

実験手法

X-RAY DIFFRACTION (2.9 Å)