Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine

doi:10.1007/s10858-017-0107-8

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	Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine
	Hou, Yaguang 2,3,4,7; Hu, Wanhui 2; Li, Xiaona 5; Skinner, John J.2; Liu, Dongsheng 2; Wuthrich, Kurt 1,2,6
刊名	JOURNAL OF BIOMOLECULAR NMR
	2017-05
卷号	68 期号:1 页码:1-6
关键词	F-19-NMR Glucagon F-19 chemical shift Solvent exposure from D2O effects
ISSN号	0925-2738
DOI	10.1007/s10858-017-0107-8
文献子类	Article
英文摘要	The amino acid 4-fluoro-l-phenylalanine (4F-Phe) was introduced at the positions of Phe6 and Phe22 in the 29-residue polypeptide hormone glucagon by expressing glucagon in E. coli in the presence of an excess of 4F-Phe. Glucagon regulates blood glucose homeostasis by interaction with the glucagon receptor (GCGR), a class B GPCR. By referencing to the 4F-Phe chemical shifts at varying D2O concentrations, the solvent exposure of the two Phe sites along the glucagon sequence was determined, showing that 4F-Phe6 was fully solvent exposed and 4F-Phe22 was only partially exposed. The incorporation of fluorine atoms in polypeptide hormones paves the way for novel studies of their interactions with membrane-spanning receptors, specifically by differentiating between effects on the solvent accessibility, the line shapes, and the chemical shifts from interactions with lipids, detergents and proteins. Studies of interactions of GCGR with ligands in solution is at this point of keen interest, given that recent crystallographic studies revealed that an apparent small molecule antagonist actually binds as an allosteric effector at a distance of similar to 20 from the orthosteric ligand binding site (Jazayeri et al., in Nature 533:274-277, 2016).
资助项目	ShanghaiTech University[00000000] ; Shanghai Municipal Government[00000000] ; Hefei Science Center[2015HSC-UE012] ; National Natural Science Foundation of China[31670733] ; Shanghai 1000-talents award[00000000]
WOS关键词	PROTEIN-COUPLED RECEPTOR ; CRYSTAL-STRUCTURE ; NMR ; ANTAGONIST ; RESONANCE ; GPCRS ; SITE
WOS研究方向	Biochemistry & Molecular Biology ; Spectroscopy
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000403406900001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272679]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Wuthrich, Kurt
作者单位	1.Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA; 2.ShanghaiTech Univ, iHuman Inst, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China; 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 6.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA; 7.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Hou, Yaguang,Hu, Wanhui,Li, Xiaona,et al. Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine[J]. JOURNAL OF BIOMOLECULAR NMR,2017,68(1):1-6.
APA	Hou, Yaguang,Hu, Wanhui,Li, Xiaona,Skinner, John J.,Liu, Dongsheng,&Wuthrich, Kurt.(2017).Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine.JOURNAL OF BIOMOLECULAR NMR,68(1),1-6.
MLA	Hou, Yaguang,et al."Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine".JOURNAL OF BIOMOLECULAR NMR 68.1(2017):1-6.