Generating thermostabilized agonist-bound GPR40/FFAR1 using virus-like particles and a label-free binding assay

Molecular Membrane Biology

Volumn 31, Issue 5, 2014, Pages 168-175

  Hirozane, Yoshihiko ^a   Motoyaji, Takashi ^a   Maru, Takamitsu ^a   Okada, Kengo ^a   Tarui, Naoki ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

GPR40 FFAR1; Size exclusion chromatography liquid chromatography mass spectroscopy based binding assay; Thermostabilized mutant; Virus like particle

Indexed keywords

FASIGLIFAM; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 40; MEMBRANE PROTEIN; BENZOFURAN DERIVATIVE; FFAR1 PROTEIN, HUMAN; LIGAND; LIPID BILAYER; PROTEIN BINDING; SULFONE; TAK-875;

ARTICLE; BINDING ASSAY; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; EMBRYO; FEMALE; HUMAN; HUMAN CELL; LIPID BILAYER; MUTANT; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR BINDING ASSAY; THERMOSTABILITY; VIRUS LIKE AGENT; CELL LINE; CHEMISTRY; GENETICS; METABOLISM; MUTATION; PROTEIN STABILITY; STAINING; TEMPERATURE;

BENZOFURANS; CELL LINE; HUMANS; LIGANDS; LIPID BILAYERS; MEMBRANE PROTEINS; MUTATION; PROTEIN BINDING; PROTEIN STABILITY; RECEPTORS, G-PROTEIN-COUPLED; STAINING AND LABELING; SULFONES; TEMPERATURE;

EID: 84905041106     PISSN: 09687688     EISSN: 14645203     Source Type: Journal    
DOI: 10.3109/09687688.2014.923588     Document Type: Article

References (31)

1. Araki T, Hirayama M, Hiroi S, Kaku K. 2012. GPR40-induced insulin secretion by the novel agonist TAK-875: First clinical findings in patients with type 2 diabetes. Diabetes Obes Metab 14: 271-278.
2. Bertheleme N, Singh S, Dowell SJ, Hubbard J, Byrne B. 2013. Loss of constitutive activity is correlated with increased thermostability of the human adenosine A2A receptor. Br J Pharmacol 169: 988-998.
3. Burant CF, Viswanathan P, Marcinak J, Cao C, Vakilynejad M, Xie B, Leifke E. 2012. TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: A phase 2, randomised, double-blind, placebocontrolled trial. Lancet 379:1403-1411.
4. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, et al. 2007. High-resolution crystal structure of an engineered human beta2-Adrenergic G protein-coupled receptor. Science 318:1258-1265.
5. Chun E, Thompson AA, Liu W, Roth CB, Griffith MT, Katritch V, et al. 2012. Fusion partner toolchest for the stabilization and crystallization of G protein-coupled receptors. Structure 20:967-976.
6. Congreve M, Andrews SP, Dore AS, Hollenstein K, Hurrell E, Langmead CJ, et al. 2012. Discovery of 1, 2, 4-Triazine derivatives as adenosine A(2A) antagonists using structure based drug design. J Med Chem 55:1898-1903.
7. Congreve M, Langmead C, Marshall FH. 2011a. The use of GPCR structures in drug design. Adv Pharmacol 62:1-36.
8. Congreve M, Rich RL, Myszka DG, Figaroa F, Siegal G, Marshall FH. 2011b. Fragment screening of stabilized G-protein-coupled receptors using biophysical methods. Methods Enzymol 493: 115-136.
9. Dore AS, Robertson N, Errey JC, Ng I, Hollenstein K, Tehan B, et al. 2011. Structure of the adenosine A(2A) receptor in complex with ZM241385 and the xanthines XAC and caffeine. Structure 19: 1283-1293.
10. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S, et al. 2003. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422:173-176.
11. Kobilka BK, Deupi X. 2007. Conformational complexity of G-proteincoupled receptors. Trends Pharmacol Sci 28:397-406.
12. Kolb P, Rosenbaum DM, Irwin JJ, Fung JJ, Kobilka BK, Shoichet BK. 2009. Structure-based discovery of beta2-Adrenergic receptor ligands. Proc Natl Acad Sci USA 106:6843-6848.
13. Lagerstrom MC, Schioth HB. 2008. Structural diversity of G proteincoupled receptors and significance for drug discovery. Nat Rev Drug Discov 7:339-357.
14. Lebon G, Bennett K, Jazayeri A, Tate CG. 2011. Thermostabilisation of an agonist-bound conformation of the human adenosine A(2A) receptor. J Mol Biol 409:298-310.
15. Leifke E, Naik H, Wu J, Viswanathan P, Demanno D, Kipnes M, Vakilynejad M. 2012. A multiple-Ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics of a novel GPR40 agonist, TAK-875, in subjects with type 2 diabetes. Clin Pharmacol Ther 92:29-39.
16. Magnani F, Shibata Y, Serrano-Vega MJ, Tate CG. 2008. Co-evolving stability and conformational homogeneity of the human adenosine A2a receptor. Proc Natl Acad Sci USA 105:10744-10749.
17. Miller JL, Tate CG. 2011. Engineering an ultra-Thermostable beta(1)-Adrenoceptor. J Mol Biol 413:628-638.
18. Muckenschnabel I, Falchetto R, Mayr LM, Filipuzzi I. 2004. SpeedScreen: Label-free liquid chromatography-mass spectrometrybased high-Throughput screening for the discovery of orphan protein ligands. Anal Biochem 324:241-249.
19. Naik H, Vakilynejad M, Wu J, Viswanathan P, Dote N, Higuchi T, Leifke E. 2012. Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of the GPR40 agonist TAK-875: Results from a double-blind, placebo-controlled single oral dose rising study in healthy volunteers. J Clin Pharmacol 52: 1007-1016.
20. Robertson N, Jazayeri A, Errey J, Baig A, Hurrell E, Zhukov A, et al. 2011. The properties of thermostabilised G protein-coupled receptors (StaRs) and their use in drug discovery. Neuropharmacology 60: 36-44.
21. Serrano-Vega MJ, Magnani F, Shibata Y, Tate CG. 2008. Conformational thermostabilization of the beta1-Adrenergic receptor in a detergentresistant form. Proc Natl Acad Sci USA 105:877-882.
22. Shibata Y, White JF, Serrano-Vega MJ, Magnani F, Aloia AL, Grisshammer R, Tate CG. 2009. Thermostabilization of the neurotensin receptor NTS1. J Mol Biol 390:262-277.
23. Tate CG. 2012. A crystal clear solution for determining G-protein-coupled receptor structures. Trends Biochem Sci 37: 343-352.
24. Tsujihata Y, Ito R, Suzuki M, Harada A, Negoro N, Yasuma T, et al.2011. TAK-875, an orally available G protein-coupled receptor 40/free fatty acid receptor 1 agonist, enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia in type 2 diabetic rats. J Pharmacol Exp Ther 339:228-237.
25. Ulrik G, Juan AB, Roland S, Elaine SB, Harel W, Brian KK. 1997. Structural instability of a constitutively active g protein-coupled receptor: Agonist-independent activation due to conformational flexibility. J Biolog Chem 272:2587-2590.
26. Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM. 2013. Molecular signatures of G-protein-coupled receptors. Nature 494:185-194.
27. Yabuki C, Komatsu H, Tsujihata Y, Maeda R, Ito R, Matsuda-Nagasumi K, et al. 2013. A novel antidiabetic drug, fasiglifam/TAK-875, acts as an ago-Allosteric modulator of FFAR1. PLoS One 8:e76280.
28. Yashiro H, Tsujihata Y, Takeuchi K, Hazama M, Johnson PR, Rorsman P. 2012. The effects of TAK-875, a selective G proteincoupled receptor 40/free fatty acid 1 agonist, on insulin and glucagon secretion in isolated rat and human islets. J Pharmacol Exp Ther 340: 483-489.
29. Zehender H, Le Goff F, Lehmann N, Filipuzzi I, Mayr LM. 2004. SpeedScreen: The 'missing link' between genomics and lead discovery. J Biomol Screen 9:498-505.
30. Zhu B, Cai G, Hall E, Freeman G. 2007. In-Fusion-Assembly: Seamless engineering of multidomain fusion proteins, modular vectors, and mutations. BioTechniques 43:354-359.
31. Zur Megede J, Chen MC, Doe B, Schaefer M, Greer CE, Selby M, et al. 2000 Increased expression and immunogenicity of sequencemodified human immunodeficiency virus type 1 gag gene. J Virol 74 2628-2635..