Title:
MUTANT G PROTEIN COUPLED RECEPTORS AND METHODS FOR SELECTING THEM
Document Type and Number:
Japanese Patent JP2018164456
Kind Code:
A
Abstract:
PROBLEM TO BE SOLVED: To provide measures to cope with two serious problems associated with crystallization of GPCR, namely, their lack of stability in detergent and the fact that they exist in multiple conformations.SOLUTION: There is disclosed herein a method for selecting G protein coupled receptor (GPCR) with increased stability, which comprises the steps of: (a) providing one or more mutants of a parent GPCR; (b) selecting a ligand that binds to the parent GPCR when the parent GPCR is residing in a particular conformation; (c) determining whether the mutant GPCR or each has increased stability with respect to binding to the selected ligand compared to the stability of the parent GPCR regarding to the binding of the selected ligand; and (d) selecting those mutants that have an increased stability compared to the parent GPCR with respect to binding of the selected ligand. Also disclosed are variants of a β-adrenergic receptor, an adenosine receptor and a neurotensin receptor.SELECTED DRAWING: None
Inventors:
HENDERSON RICHARD
TATE CHRISTOPHER GORDON
MAGNANI FRANCESCA
SERRANO-VEGA MARIA JOSEFA
SHIBATA YOKO
WARNE ANTHONY JOHANNES
WEIR MALCOLM PETER
TATE CHRISTOPHER GORDON
MAGNANI FRANCESCA
SERRANO-VEGA MARIA JOSEFA
SHIBATA YOKO
WARNE ANTHONY JOHANNES
WEIR MALCOLM PETER
Application Number:
JP2018135756A
Publication Date:
October 25, 2018
Filing Date:
July 19, 2018
Export Citation:
Assignee:
HEPTARES THERAPEUTICS LTD
International Classes:
C12N15/12; C07K14/705; C12N1/15; C12N1/19; C12N1/21; C12N5/10
Other References:
白石 充典: "Ｇタンパク質共役型受容体の構造解析に向けた戦略 〜ヒスタミンＨ１受容体を例に〜", ＹＡＫＵＧＡＫＵ ＺＡＳＳＨＩ, vol. 133, JPN6018004117, 2013, pages 539 - 547, ISSN: 0004306193
WARNE T. ET AL.: "Structure of a beta1-adrenergic G-protein-coupled receptor", NATURE, vol. Vol. 454(7203), JPN6020025046, 2008, pages 486 - 491, XP037696526, ISSN: 0004306194, DOI: 10.1038/nature07101
ゲノム情報解析から概観するＧＰＣＲプロテオーム: "諏訪牧子", ファルマシア, vol. Vol. 50(9), JPN6020025047, 2014, pages 888 - 892, ISSN: 0004306195
D'ANTONA A. M. ET AL.: "Mutations of CB1 T210 produce active and inactive receptor forms: correlations with ligand affinity,", BIOCHEMISTRY, vol. Vol. 45(17), JPN6020025048, 2006, pages 5606 - 5617, ISSN: 0004306196
EUROPEAN JOURNAL OF BIOCHEMISTRY. 2002, VOL.269, NO.1, P.82-92, JPN6010051044, ISSN: 0004074722
BRAIN RESEARCH. 2006, VOL.1108, NO.1, P.1-11, JPN6010028841, ISSN: 0004074723
THE JOURNAL OF BIOLOGICAL CHEMISTRY. 1998, VOL.273, NO.26, P.16351-16357, JPN6010051045, ISSN: 0004074724
THE JOURNAL OF BIOLOGICAL CHEMISTRY. 2000, VOL.275, NO.1, P.328-336, JPN6010051047, ISSN: 0004074725
MOLECULAR PHARMACOLOGY. 2006, VOL.70, NO.3, P.838-850, JPN6010051042, ISSN: 0004074726
WARNE T. ET AL.: "Structure of a beta1-adrenergic G-protein-coupled receptor", NATURE, vol. Vol. 454(7203), JPN6020025046, 2008, pages 486 - 491, XP037696526, ISSN: 0004306194, DOI: 10.1038/nature07101
ゲノム情報解析から概観するＧＰＣＲプロテオーム: "諏訪牧子", ファルマシア, vol. Vol. 50(9), JPN6020025047, 2014, pages 888 - 892, ISSN: 0004306195
D'ANTONA A. M. ET AL.: "Mutations of CB1 T210 produce active and inactive receptor forms: correlations with ligand affinity,", BIOCHEMISTRY, vol. Vol. 45(17), JPN6020025048, 2006, pages 5606 - 5617, ISSN: 0004306196
EUROPEAN JOURNAL OF BIOCHEMISTRY. 2002, VOL.269, NO.1, P.82-92, JPN6010051044, ISSN: 0004074722
BRAIN RESEARCH. 2006, VOL.1108, NO.1, P.1-11, JPN6010028841, ISSN: 0004074723
THE JOURNAL OF BIOLOGICAL CHEMISTRY. 1998, VOL.273, NO.26, P.16351-16357, JPN6010051045, ISSN: 0004074724
THE JOURNAL OF BIOLOGICAL CHEMISTRY. 2000, VOL.275, NO.1, P.328-336, JPN6010051047, ISSN: 0004074725
MOLECULAR PHARMACOLOGY. 2006, VOL.70, NO.3, P.838-850, JPN6010051042, ISSN: 0004074726
Attorney, Agent or Firm:
Yasuhiko Murayama
Shinya Mitsuhiro
Tatsuhiko Abe
Shinya Mitsuhiro
Tatsuhiko Abe