Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1

doi:10.1016/j.cell.2015.06.002

KMS > iHuman研究所 > 特聘教授组 > Raymond Stevens组

	Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1
	Chrencik, Jill E.1; Roth, Christopher B.1; Terakado, Masahiko 2; Kurata, Haruto 2; Omi, Rie 2; Kihara, Yasuyuki 6; Warshaviak, Dora 3; Nakade, Shinji 7; Asmar-Rovira, Guillermo 1; Mileni, Mauro 1; Mizuno, Hirotaka 6,7; Griffith, Mark T.1; Rodgers, Caroline 1; Han, Gye Won 4,5; Velasquez, Jeffrey 4,5; Chun, Jerold 6; Stevens, Raymond C.4,5,8 ; Hanson, Michael A.1
	2015-06-18
发表期刊	CELL (IF:45.5[JCR-2023],49.0[5-Year])
ISSN	0092-8674
卷号	161 期号:7 页码:1633-1643
发表状态	已发表
DOI	10.1016/j.cell.2015.06.002
摘要	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 LPA(1) 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 LPA(1) binding pocket from the extracellular space contrasting with the proposed access for the sphingosine 1-phosphate receptor. Characteristics of the LPA(1) 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.
收录类别	SCI
语种	英语
资助项目	NIH[MH051699] ; NIH[NS082092] ; NIH[NS084398] ; NIH[U54 GM094618] ; NIH[GPCR-235]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000356618200019
出版者	CELL PRESS
WOS关键词	PROTEIN-COUPLED RECEPTORS ; MOLECULAR-DYNAMICS ; MEMBRANE-PROTEINS ; CANNABINOID CB1 ; LPA(1) ; CELLS ; AUTOTAXIN ; BRAIN ; PH ; VZG-1/LP(A1)/EDG-2
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2196
专题	iHuman研究所_特聘教授组_Raymond Stevens组 iHuman研究所
通讯作者	Hanson, Michael A.
作者单位	1.Receptos, Dept Struct Discovery, San Diego, CA 92121 USA 2.Ono Pharmaceut Co Ltd, Med Chem Res Labs, Osaka 6188585, Japan 3.Schrodinger Inc, New York, NY 10036 USA 4.Univ So Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA 90089 USA 5.Univ So Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA 6.Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA 7.Ono Pharmaceut Co Ltd, Exploratory Res Labs, Ibaraki 3004247, Japan 8.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Chrencik, Jill E.,Roth, Christopher B.,Terakado, Masahiko,et al. Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1[J]. CELL,2015,161(7):1633-1643.
APA	Chrencik, Jill E..,Roth, Christopher B..,Terakado, Masahiko.,Kurata, Haruto.,Omi, Rie.,...&Hanson, Michael A..(2015).Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1.CELL,161(7),1633-1643.
MLA	Chrencik, Jill E.,et al."Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1".CELL 161.7(2015):1633-1643.