Comparing Class A GPCRs to bitter taste receptors: Structural motifs, ligand interactions and agonist-to-antagonist ratios

Methods in Cell Biology

Volumn 132, Issue , 2016, Pages 401-427

  Di Pizio, Antonella ^a   Levitx, Anat ^b   Slutzki, Michal ^a   Behrens, Maik ^c   Karamanjj, Rafik ^d   Niv, Masha Y ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c GERMAN INSTITUTE OF HUMAN NUTRITION   (Germany)

^d AL QUDS UNIVERSITY   (Palestine)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; LIGAND; PROTEIN BINDING;

AGONISTS; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMISTRY; COMPARATIVE STUDY; DRUG EFFECTS; HUMAN; MOLECULAR MODEL; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; TASTE;

BINDING SITES; HUMANS; LIGANDS; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, G-PROTEIN-COUPLED; TASTE;

EID: 84951743686     PISSN: 0091679X     EISSN: None     Source Type: Book Series    
DOI: 10.1016/bs.mcb.2015.10.005     Document Type: Article

References (115)

1. Audet, M., Bouvier, M. (2012). Restructuring G-protein- coupled receptor activation. Cell, 151(1), 14e23.
2. Ballesteros, J. A., Weinstein, H. (1995). Integrated methods for the construction of threedimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods in Neurosciences, 25, 366e428.
3. Biarnes, X., Marchiori, A., Giorgetti, A., Lanzara, C., Gasparini, P., Carloni, P., et al. (2010). Insights into the binding of phenylthiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor. PLoS One, 5(8), e12394.
4. Bjarnadottir, T. K., Gloriam, D. E., Hellstrand, S. H., Kristiansson, H., Fredriksson, R., Schioth, H. B. (2006). Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Genomics, 88(3), 263e273.
5. Born, S., Levit, A., Niv, M. Y., Meyerhof, W., Behrens, M. (2013). The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands. The Journal of Neuroscience, 33(1), 201e213.
6. Breslin, P. A., Beauchamp, G. K. (1995). Suppression of bitterness by sodium: variation among bitter taste stimuli. Chemical Senses, 20(6), 609e623.
7. Brockhoff, A., Behrens, M., Massarotti, A., Appendino, G., Meyerhof, W. (2007). Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. Journal of Agricultural and Food Chemistry, 55(15), 6236e6243.
8. Brockhoff, A., Behrens, M., Niv, M. Y., Meyerhof, W. (2010). Structural requirements of bitter taste receptor activation. Proceedings of the National Academy of Sciences of the United States of America, 107(24), 11110e11115.
9. Brockhoff, A., Behrens, M., Roudnitzky, N., Appendino, G., Avonto, C., Meyerhof, W. (2011). Receptor agonism and antagonism of dietary bitter compounds. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 31(41), 14775e14782.
10. Buck, L., Axel, R. (1991). A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell, 65(1), 175e187.
11. Caicedo, A., Pereira, E., Margolskee, R. F., Roper, S. D. (2003). Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli. The Journal of Neuroscience, 23(30), 9947e9952.
12. van Cauwenberge, P., Bachert, C., Passalacqua, G., Bousquet, J., Canonica, G. W., Durham, S. R., et al. (2000). Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology. Allergy, 55(2), 116e134.
13. Chothia, C., Lesk, A. M. (1986). The relation between the divergence of sequence and structure in proteins. The EMBO Journal, 5(4), 823e826.
14. Civelli, O., Reinscheid, R. K., Zhang, Y., Wang, Z., Fredriksson, R., Schioth, H. B. (2013). G protein-coupled receptor deorphanizations. Annual Review of Pharmacology and Toxicology, 53, 127e146.
15. Clark, A. A., Liggett, S. B., Munger, S. D. (2012). Extraoral bitter taste receptors as mediators of off-target drug effects. The FASEB Journal, 26(12), 4827e4831.
16. Dai,W., You, Z., Zhou, H., Zhang, J., Hu, Y. (2011). Structure-function relationships of the human bitter taste receptor hTAS2R1: insights from molecular modeling studies. Journal of Receptor and Signal Transduction Research, 31(3), 229e240.
17. Dalton, R. P., Lomvardas, S. (2015). Chemosensory receptor specificity and regulation. Annual Review of Neuroscience, 38, 331e349.
18. Davies, M. N., Secker, A., Halling-Brown, M., Moss, D. S., Freitas, A. A., Timmis, J., et al. (2008). GPCRTree: online hierarchical classification of GPCR function. BMC Research Notes, 1, 67.
19. DeSimone, J. A., Dubois, G. E., Lyall, V. (2015). Chemical modulators of taste. Handbook of olfaction and gustation (pp. 665e684). John Wiley and Sons, Inc.
20. DeWire, S. M., Violin, J. D. (2011). Biased ligands for better cardiovascular drugs: dissecting G-protein-coupled receptor pharmacology. Circulation Research, 109(2), 205e216.
21. Di Pizio, A., Niv, M. Y. (2014). Computational studies of smell and taste receptors. Israel Journal of Chemistry, 54(8-9), 1205e1218.
22. Di Pizio, A., Niv, M. Y. (2015). Promiscuity and selectivity of bitter molecules and their receptors. Bioorganic and Medicinal Chemistry, 23(14), 4082e4091.
23. Dore, A. S., Okrasa, K., Patel, J. C., Serrano-Vega, M., Bennett, K., Cooke, R. M., et al. (2014). Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature, 511(7511), 557e562.
24. Drewnowski, A., Gomez-Carneros, C. (2000). Bitter taste, phytonutrients, and the consumer: a review. The American Journal of Clinical Nutrition, 72(6), 1424e1435.
25. Dror, R. O., Arlow, D. H., Borhani, D. W., Jensen, M. O., Piana, S., Shaw, D. E. (2009). Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations. Proceedings of the National Academy of Sciences of the United States of America, 106(12), 4689e4694.
26. Dror, R. O., Green, H. F., Valant, C., Borhani, D. W., Valcourt, J. R., Pan, A. C., et al. (2013). Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs. Nature, 503(7475), 295e299.
27. Fletcher, J. N., Kinghorn, A. D., Slack, J. P., McCluskey, T. S., Odley, A., Jia, Z. (2011). In vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31. Journal of Agricultural and Food Chemistry, 59(24), 13117e13121.
28. Floriano, W. B., Hall, S., Vaidehi, N., Kim, U., Drayna, D., Goddard, W. A., 3rd (2006). Modeling the human PTC bitter-taste receptor interactions with bitter tastants. Journal of Molecular Modeling, 12(6), 931e941.
29. Fredriksson, R., Lagerstrom, M. C., Lundin, L. G., Schioth, H. B. (2003). The G-proteincoupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Molecular Pharmacology, 63(6), 1256e1272.
30. Garland, S. L. (2013). Are GPCRs still a source of new targets? Journal of Biomolecular Screening, 18(9), 947e966.
31. Gether, U., Kobilka, B. K. (1998). G protein-coupled receptors. II. Mechanism of agonist activation. The Journal of Biological Chemistry, 273(29), 17979e17982.
32. Granier, S., Kobilka, B. (2012). A new era of GPCR structural and chemical biology. Nature Chemical Biology, 8(8), 670e673.
33. Haga, K., Kruse, A. C., Asada, H., Yurugi-Kobayashi, T., Shiroishi, M., Zhang, C., et al. (2012). Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature, 482(7386), 547e551.
34. Hejaz, H., Karaman, R., Khamis, M. (2012). Computer-assisted design for paracetamol masking bitter taste prodrugs. Journal of Molecular Modeling, 18(1), 103e114.
35. Hochheimer, A., Krohn, M., Rudert, K., Riedel, K., Becker, S., Thirion, C., et al. (2014). Endogenous gustatory responses and gene expression profile of stably proliferating human taste cells isolated from fungiform papillae. Chemical Senses, 39(4), 359e377.
36. Hofmann, K. P., Scheerer, P., Hildebrand, P. W., Choe, H. W., Park, J. H., Heck, M., et al. (2009). A G protein-coupled receptor at work: the rhodopsin model. Trends in Biochemical Sciences, 34(11), 540e552.
37. Hollenstein, K., Kean, J., Bortolato, A., Cheng, R. K., Dore, A. S., Jazayeri, A., et al. (2013). Structure of class B GPCR corticotropin-releasing factor receptor 1. Nature, 499(7459), 438e443.
38. Horn, F., Bettler, E., Oliveira, L., Campagne, F., Cohen, F. E., Vriend, G. (2003). GPCRDB information system for G protein-coupled receptors. Nucleic Acids Research, 31(1), 294e297.
39. Horn, F., Weare, J., Beukers, M. W., Horsch, S., Bairoch, A., Chen, W., et al. (1998). GPCRDB: an information system for G protein-coupled receptors. Nucleic Acids Research, 26(1), 275e279.
40. Isberg, V., de Graaf, C., Bortolato, A., Cherezov, V., Katritch, V., Marshall, F. H., et al. (2015). Generic GPCR residue numbers e aligning topology maps while minding the gaps. Trends in Pharmacological Sciences, 36(1), 22e31.
41. Isberg, V., Vroling, B., van der Kant, R., Li, K., Vriend, G., Gloriam, D. (2014). GPCRDB: an information system for G protein-coupled receptors. Nucleic Acids Research, 42(Database issue), D422eD425.
42. Karaman, R. (2013). Prodrugs for masking bitter taste of antibacterial drugsea computational approach. Journal of Molecular Modeling, 19(6), 2399e2412.
43. Katritch, V., Cherezov, V., Stevens, R. C. (2012). Diversity and modularity of G proteincoupled receptor structures. Trends in Pharmacological Sciences, 33(1), 17e27.
44. Katritch, V., Cherezov, V., Stevens, R. C. (2013). Structure-function of the G proteincoupled receptor superfamily. Annual Review of Pharmacology and Toxicology, 53, 531e556.
45. Katritch, V., Fenalti, G., Abola, E. E., Roth, B. L., Cherezov, V., Stevens, R. C. (2014). Allosteric sodium in class A GPCR signaling. Trends in Biochemical Sciences, 39(5), 233e244.
46. Keast, R. S., Breslin, P. A. (2002). Modifying the bitterness of selected oral pharmaceuticals with cation and anion series of salts. Pharmaceutical Research, 19(7), 1019e1026.
47. Knox, C., Law, V., Jewison, T., Liu, P., Ly, S., Frolkis, A., et al. (2011). DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Research, 39(Database issue), D1035eD1041.
48. Kobilka, B. (2013). The structural basis of G-protein-coupled receptor signaling (Nobel Lecture). Angewandte Chemie International Edition in English, 52(25), 6380e6388.
49. Kohlhoff, K. J., Shukla, D., Lawrenz, M., Bowman, G. R., Konerding, D. E., Belov, D., et al. (2014). Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways. Nature Chemistry, 6(1), 15e21.
50. Kowalsman, N., Niv, M. Y. (2014). GPCR and company: databases and servers for GPCRs and interacting partners. Advances in Experimental Medicine and Biology, 796, 185e204.
51. Krumm, B. E., White, J. F., Shah, P., Grisshammer, R. (2015). Structural prerequisites for G-protein activation by the neurotensin receptor. Nature Communications, 6, 7895.
52. Kruse, A. C., Hu, J., Pan, A. C., Arlow, D. H., Rosenbaum, D. M., Rosemond, E., et al. (2012). Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature, 482(7386), 552e556.
53. Kruse, A. C., Ring, A. M., Manglik, A., Hu, J., Hu, K., Eitel, K., et al. (2013). Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature, 504(7478), 101e106.
54. Kufareva, I., Rueda, M., Katritch, V., Stevens, R. C., Abagyan, R., GPCR Dock 2010 Participants. (2011). Status of GPCR modeling and docking as reflected by communitywide GPCR Dock 2010 assessment. Structure, 19(8), 1108e1126.
55. Lagerstrom, M. C., Schioth, H. B. (2008). Structural diversity of G protein-coupled receptors and significance for drug discovery. Nature Reviews Drug Discovery, 7(4), 339e357.
56. Levit, A., Barak, D., Behrens, M., Meyerhof, W., Niv, M. Y. (2012). Homology modelassisted elucidation of binding sites in GPCRs. Methods in Molecular Biology, 914, 179e205.
57. Levit, A., Beuming, T., Krilov, G., Sherman, W., Niv, M. Y. (2014). Predicting GPCR promiscuity using binding site features. Journal of Chemical Information and Modeling, 54(1), 184e194.
58. Levit, A., Nowak, S., Peters, M., Wiener, A., Meyerhof, W., Behrens, M., et al. (2014). The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. The FASEB Journal, 28(3), 1181e1197.
59. Ley, J. P., Dessoy, M., Paetz, S., Blings, M., Hoffmann-Lucke, P., Reichelt, K. V., et al. (2012). Identification of enterodiol as a masker for caffeine bitterness by using a pharmacophore model based on structural analogues of homoeriodictyol. Journal of Agricultural and Food Chemistry, 60(25), 6303e6311.
60. Ley, J. P., Krammer, G., Reinders, G., Gatfield, I. L., Bertram, H.-J. (2005). Evaluation of bitter masking flavanones from Herba Santa (Eriodictyon californicum (H. and A.) Torr., Hydrophyllaceae). Journal Agricultural and Food Chemistry, 53(15), 6061e6066.
61. Li, J., Pan, L., Fletcher, J. N., Lv, W., Deng, Y., Vincent, M. A., et al. (2014). In vitro evaluation of potential bitterness-masking terpenoids from the Canada goldenrod (Solidago canadensis). Journal of Natural Products, 77(7), 1739e1743.
62. Liu, W., Chun, E., Thompson, A. A., Chubukov, P., Xu, F., Katritch, V., et al. (2012). Structural basis for allosteric regulation of GPCRs by sodium ions. Science, 337(6091), 232e236.
63. Luttrell, L. M. (2014). Minireview: More than just a hammer: ligand "bias" and pharmaceutical discovery. Molecular Endocrinology, 28(3), 281e294.
64. Malbon, C. C. (2004). Frizzleds: new members of the superfamily of G-protein-coupled receptors. Frontiers in Bioscience: A Journal and Virtual Library, 9, 1048e1058.
65. Marchiori, A., Capece, L., Giorgetti, A., Gasparini, P., Behrens, M., Carloni, P., et al. (2013). Coarse-grained/molecular mechanics of the TAS2R38 bitter taste receptor: experimentally- validated detailed structural prediction of agonist binding. PLoS One, 8(5), e64675.
66. Marti-Solano, M., Sanz, F., Pastor, M., Selent, J. (2014). A dynamic view of molecular switch behavior at serotonin receptors: implications for functional selectivity. PLoS One, 9(10), e109312.
67. McLaughlin, S. K., McKinnon, P. J., Robichon, A., Spickofsky, N., Margolskee, R. F. (1993). Gustducin and transducin: a tale of two G proteins. Ciba Foundation Symposium, 179, 186e196, discussion 196-200.
68. Meltzer, H. Y., Roth, B. L. (2013). Lorcaserin and pimavanserin: emerging selectivity of serotonin receptor subtype-targeted drugs. The Journal of Clinical Investigation, 123(12), 4986e4991.
69. Meyerhof, W. (2005). Elucidation of mammalian bitter taste. Reviews of Physiology, Biochemistry and Pharmacology, 154, 37e72.
70. Miguet, L., Zhang, Z., Grigorov, M. G. (2006). Computational studies of ligand-receptor interactions in bitter taste receptors. Journal of Receptor and Signal Transduction Research, 26(5e6), 611e630.
71. Moreira, I. S. (2014). Structural features of the G-protein/GPCR interactions. Biochimca et Biophysica Acta, 1840(1), 16e33.
72. Mueller, K. L., Hoon, M. A., Erlenbach, I., Chandrashekar, J., Zuker, C. S., Ryba, N. J. P. (2005). The receptors and coding logic for bitter taste. Nature, 434(7030), 225e229.
73. Nelson, G., Hoon, M. A., Chandrashekar, J., Zhang, Y., Ryba, N. J., Zuker, C. S. (2001). Mammalian sweet taste receptors. Cell, 106(3), 381e390.
74. Neves, S. R., Ram, P. T., Iyengar, R. (2002). G protein pathways. Science, 296(5573), 1636e1639.
75. Niv, M. Y., Skrabanek, L., Filizola, M., Weinstein, H. (2006). Modeling activated states of GPCRs: the rhodopsin template. Journal of Computer-Aided Molecular Design, 20, 437e448.
76. Nordstrom, K. J., Sallman Almen, M., Edstam, M. M., Fredriksson, R., Schioth, H. B. (2011). Independent HHsearch, NeedlemaneWunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families. Molecular Biology and Evolution, 28(9), 2471e2480.
77. Nygaard, R., Frimurer, T. M., Holst, B., Rosenkilde, M. M., Schwartz, T.W. (2009). Ligand binding and micro-switches in 7TM receptor structures. Trends in Pharmacological Sciences, 30(5), 249e259.
78. Ossipov,M.H., Lai, J.,King, T.,Vanderah, T. W.,Malan, T. P., Jr., Hruby,V. J., et al. (2004). Antinociceptive and nociceptive actions of opioids. Journal of Neurobiology, 61(1), 126e148.
79. Ozeck, M., Brust, P., Xu, H., Servant, G. (2004). Receptors for bitter, sweet and umami taste couple to inhibitory G protein signaling pathways. European Journal of Pharmacology, 489(3), 139e149.
80. Pronin, A. N., Tang, H., Connor, J., Keung, W. (2004). Identification of ligands for two human bitter T2R receptors. Chemical Senses, 29(7), 583e593.
81. Pydi, S. P., Bhullar, R. P., Chelikani, P. (2012). Constitutively active mutant gives novel insights into the mechanism of bitter taste receptor activation. Journal of Neurochemistry, 122(3), 537e544.
82. Pydi, S. P., Bhullar, R. P., Chelikani, P. (2014). Constitutive activity of bitter taste receptors (T2Rs). Advances in Pharmacology (San Diego, Calif.), 70, 303e326.
83. Pydi, S. P., Jaggupilli, A., Nelson, K. M., Abrams, S. R., Bhullar, R. P., Loewen, M. C., et al. (2015). Abscisic acid acts as a blocker of the bitter taste g protein-coupled receptor T2R4. Biochemistry, 54(16), 2622e2631.
84. Pydi, S. P., Sobotkiewicz, T., Billakanti, R., Bhullar, R. P., Loewen, M. C., Chelikani, P. (2014). Amino acid derivatives as bitter taste receptor (T2R) blockers. The Journal of Biological Chemistry, 289(36), 25054e25066.
85. Pydi, S. P., Upadhyaya, J., Singh, N., Pal Bhullar, R., Chelikani, P. (2012). Recent advances in structure and function studies on human bitter taste receptors. Current Protein and Peptide Science, 13(6), 501e508.
86. Rasmussen, S. G., DeVree, B. T., Zou, Y., Kruse, A. C., Chung, K. Y., Kobilka, T. S., et al. (2011). Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature, 477(7366), 549e555.
87. Reichling, C., Meyerhof,W., Behrens, M. (2008). Functions of human bitter taste receptors depend on N-glycosylation. Journal of Neurochemistry, 106(3), 1138e1148.
88. Roland, W. S. U., Gouka, R. J., Gruppen, H., Driesse, M., van Buren, L., Smit, G., et al. (2014). 6-Methoxyflavanones as bitter taste receptor blockers for hTAS2R39. PLoS One, 9(4), e94451.
89. Roland, W. S., Sanders, M. P., van Buren, L., Gouka, R. J., Gruppen, H., Vincken, J. P., et al. (2015). Snooker structure-based pharmacophore model explains differences in agonist and blocker binding to bitter receptor hTAS2R39. PLoS One, 10(3), e0118200.
90. Rosenbaum, D. M., Rasmussen, S. G., Kobilka, B. K. (2009). The structure and function of G-protein-coupled receptors. Nature, 459(7245), 356e363.
91. Rost, B. (1999). Twilight zone of protein sequence alignments. Protein Engineering, 12(2), 85e94.
92. Sainz, E., Cavenagh, M. M., Gutierrez, J., Battey, J. F., Northup, J. K., Sullivan, S. L. (2007). Functional characterization of human bitter taste receptors. Biochemical Journal, 403(3), 537e543.
93. Sakurai, T., Misaka, T., Ishiguro, M., Masuda, K., Sugawara, T., Ito, K., et al. (2010). Characterization of the beta-D-glucopyranoside binding site of the human bitter taste receptor hTAS2R16. The Journal of Biological Chemistry, 285(36), 28373e28378.
94. Sandal, M., Behrens, M., Brockhoff, A., Musiani, F., Giorgetti, A., Carloni, P., et al. (2015). Evidence for a transient additional ligand binding site in the TAS2R46 bitter taste receptor. Journal of Chemical Theory and Computation, 11(9), 4439e4449.
95. Shonberg, J., Kling, R. C., Gmeiner, P., Lober, S. (2015). GPCR crystal structures: medicinal chemistry in the pocket. Bioorganic and Medicinal Chemistry, 23(14), 3880e3906.
96. Simon, M. I., Strathmann, M. P., Gautam, N. (1991). Diversity of G proteins in signal transduction. Science (New York, NY), 252(5007), 802e808.
97. Singh, N., Pydi, S. P., Upadhyaya, J., Chelikani, P. (2011). Structural basis of activation of bitter taste receptor T2R1 and comparison with Class A G-protein-coupled receptors (GPCRs). The Journal of Biological Chemistry, 286(41), 36032e36041.
98. Siu, F. Y., He, M., de Graaf, C., Han, G.W., Yang, D., Zhang, Z., et al. (2013). Structure of the human glucagon class B G-protein-coupled receptor. Nature, 499(7459), 444e449.
99. Slack, J. P., Brockhoff, A., Batram, C., Menzel, S., Sonnabend, C., Born, S., et al. (2010). Modulation of bitter taste perception by a small molecule hTAS2R antagonist. Current Biology: CB, 20(12), 1104e1109.
100. Steyaert, J., Kobilka, B. K. (2011). Nanobody stabilization of G protein-coupled receptor conformational states. Current Opinion in Structural Biology, 21(4), 567e572.
101. Strasser, A., Wittmann, H.-J., Schneider, E., Seifert, R. (2015). Modulation of GPCRs by monovalent cations and anions. Naunyn-Schmiedeberg's Archives of Pharmacology, 388(3), 363e380.
102. Takeda, S., Kadowaki, S., Haga, T., Takaesu, H., Mitaku, S. (2002). Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Letters, 520(1e3), 97e101.
103. Tan, J., Abrol, R., Trzaskowski, B., Goddard, W. A., 3rd (2012). 3D structure prediction of TAS2R38 bitter receptors bound to agonists phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP). Journal of Chemical Information and Modeling, 52(7), 1875e1885.
104. Tehan, B. G., Bortolato, A., Blaney, F. E.,Weir, M. P., Mason, J. S. (2014). Unifying family a GPCR theories of activation. Pharmacology and Therapeutics, 143(1), 51e60.
105. Topiol, S., Sabio, M. (2015). The role of experimental and computational structural approaches in 7TM drug discovery. Expert Opinion on Drug Discovery, 1e14.
106. Trzaskowski, B., Latek, D., Yuan, S., Ghoshdastider, U., Debinski, A., Filipek, S. (2012). Action of molecular switches in GPCRsetheoretical and experimental studies. Current Medical Chemistry, 19(8), 1090e1109.
107. Vanni, S., Neri, M., Tavernelli, I., Rothlisberger, U. (2009). Observation of "ionic lock" formation in molecular dynamics simulations of wild-type beta 1 and beta 2 adrenergic receptors. Biochemistry, 48(22), 4789e4797.
108. Venkatakrishnan, A. J., Deupi, X., Lebon, G., Tate, C. G., Schertler, G. F., Babu, M. M. (2013). Molecular signatures of G-protein-coupled receptors. Nature, 494(7436), 185e194.
109. Venkatakrishnan, A. J., Flock, T., Prado, D. E., Oates, M. E., Gough, J., Madan Babu, M. (2014). Structured and disordered facets of the GPCR fold. Current Opinion Structural Biology, 27, 129e137.
110. Wheatley, M., Hawtin, S. R. (1999). Glycosylation of G-protein-coupled receptors for hormones central to normal reproductive functioning: its occurrence and role. Human Reproduction Update, 5(4), 356e364.
111. Wheatley, M.,Wootten, D., Conner,M. T., Simms, J., Kendrick, R., Logan, R. T., et al. (2012). Lifting the lid on GPCRs: the role of extracellular loops. British Journal of Pharmacology, 165(6), 1688e1703.
112. Wiener, A., Shudler, M., Levit, A., Niv, M. Y. (2012). BitterDB: a database of bitter compounds. Nucleic Acids Research, 40(Database issue), D413eD419.
113. Wong, S. K. F. (2003). G protein selectivity is regulated by multiple intracellular regions of GPCRs. Neuro-Signals, 12(1), 1e12.
114. Yuan, S., Filipek, S., Palczewski, K., Vogel, H. (2014). Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway. Nature communications, 5, 4733.
115. Yuan, S., Hu, Z., Filipek, S., Vogel, H. (2015). W246(6.48) opens a gate for a continuous intrinsic water pathway during activation of the adenosine A2A receptor. Angewandte Chemie International Edition in English, 54(2), 556e559.