Ligand binding modes from low resolution GPCR models and mutagenesis: Chicken bitter taste receptor as a test-case

Scientific Reports

Volumn 7, Issue 1, 2017, Pages

  Di Pizio, Antonella ^a   Kruetzfeldt, Louisa Marie ^b   Cheled Shoval, Shira ^a   Meyerhof, Wolfgang ^b   Behrens, Maik ^b   Niv, Masha Y ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b GERMAN INSTITUTE OF HUMAN NUTRITION   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; LIGAND; PROTEIN BINDING; QUININE;

AMINO ACID SEQUENCE; ANALOGS AND DERIVATIVES; ANIMAL; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; CHICKEN; CONFORMATION; DRUG DEVELOPMENT; GENETICS; HYDROGEN BOND; METABOLISM; MUTAGENESIS; STRUCTURE ACTIVITY RELATION; TASTE BUD;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CHICKENS; DRUG DISCOVERY; HYDROGEN BONDING; LIGANDS; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; MUTAGENESIS; PROTEIN BINDING; QUININE; RECEPTORS, G-PROTEIN-COUPLED; STRUCTURE-ACTIVITY RELATIONSHIP; TASTE BUDS;

EID: 85027504973     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-017-08344-9     Document Type: Article

References (48)

1. Reed, D. R. & Knaapila, A. Genetics of taste and smell: poisons and pleasures. Prog Mol Biol Transl Sci 94, 213-240 (2010).
2. Steiner, J. E., Glaser, D., Hawilo, M. E. & Berridge, K. C. Comparative expression of hedonic impact: affective reactions to taste by human infants and other primates. Neurosci Biobehav Rev 25, 53-74 (2001).
3. Cheled-Shoval, S. L., Behrens, M., Meyerhof, W., Niv, M. Y. & Uni, Z. Perinatal administration of a bitter tastant influences gene expression in chicken palate and duodenum. J Agric Food Chem 62, 12512-12520 (2014).
4. Boughter, J. D. Jr., Raghow, S., Nelson, T. M. & Munger, S. D. Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli. BMC Genet 6, 36 (2005).
5. Meyerhof, W. et al. The molecular receptive ranges of human TAS2R bitter taste receptors. Chemical senses 35, 157-170 (2010).
6. Behrens, M. & Meyerhof, W. Oral and extraoral bitter taste receptors. Results Probl Cell Differ 52, 87-99 (2010).
7. Rowland, H.M., Rockwell Parker, M., Jiang, P., Reed, D.R. & Beauchamp, G.K. Comparative Taste Biology with Special Focus on Birds and Reptiles. 957-982 (2015).
8. Roura, E., Baldwin, M. W. & Klasing, K. C. The avian taste system: Potential implications in poultry nutrition. Anim Feed Sci Tech 180, 1-9 (2013).
9. Behrens, M., Korsching, S. I. & Meyerhof, W. Tuning Properties of Avian and Frog Bitter Taste Receptors Dynamically Fit Gene Repertoire sizes. Molecular biology and evolution 31, 3216-3227 (2014).
10. Di Pizio, A. & Niv, M. Y. Computational Studies of Smell and Taste Receptors. Israel Journal of Chemistry 54, 1205-1218 (2014).
11. Di Pizio, A. et al. Comparing Class A GPCRs to bitter taste receptors: Structural motifs, ligand interactions and agonist-to-antagonist ratios. Methods in cell biology 132, 401-427 (2016).
12. Cheled-Shoval, S. L., Druyan, S. & Uni, Z. Bitter, sweet and umami taste receptors and downstream signaling effectors: Expression in embryonic and growing chicken gastrointestinal tract. Poultry science 94, 1928-1941 (2015).
13. Dey, B. et al. Identification of functional bitter taste receptors and their antagonist in chickens. Biochemical and biophysical research communications (2016).
14. Karaman, R. et al. Probing the Binding Pocket of the Broadly Tuned Human Bitter Taste Receptor TAS2R14 by Chemical Modification of Cognate Agonists. Chemical biology & drug design 88, 66-75 (2016).
15. Mente, S., Guilmette, E., Salafia, M. & Gray, D. Dopamine D1 receptor-agonist interactions: A mutagenesis and homology modeling study. Bioorganic & medicinal chemistry letters 25, 2106-2111 (2015).
16. Huang, X. P. et al. Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65. Nature 527, 477-483 (2015).
17. Kryshtafovych, A., Fidelis, K. & Moult, J. CASP10 results compared to those of previous CASP experiments. Proteins (2013).
18. Levit, A., Barak, D., Behrens, M., Meyerhof, W. & Niv, M. Y. Homology model-assisted elucidation of binding sites in GPCRs. Methods Mol Biol 914, 179-205 (2012).
19. Born, S., Levit, A., Niv, M. Y., Meyerhof, W. & Behrens, M. The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands. J Neurosci 33, 201-213 (2013).
20. Brockhoff, A., Behrens, M., Niv, M. Y. & Meyerhof, W. Structural requirements of bitter taste receptor activation. Proc Natl Acad Sci USA 107, 11110-11115 (2010).
21. Marchiori, A. et al. Coarse-grained/molecular mechanics of the TAS2R38 bitter taste receptor: experimentally-validated detailed structural prediction of agonist binding. PLoS One 8, e64675 (2013).
22. Yarnitzky, T., Levit, A. & Niv, M. Y. Homology modeling of G-protein-coupled receptors with X-ray structures on the rise. Curr Opin Drug Discov Devel 13, 317-325 (2010).
23. Thomas, T. et al. Homology Modeling of Human Muscarinic Acetylcholine Receptors. J Chem Inf Model (2013).
24. Heifetz, A. et al. Toward an understanding of agonist binding to human Orexin-1 and Orexin-2 receptors with G-protein-coupled receptor modeling and site-directed mutagenesis. Biochemistry 52, 8246-8260 (2013).
25. Musiani, F., Giorgetti, A. & Carloni, P. Molecular Mechanics/Coarse-Grained Simulations as a Structural Prediction Tool for GPCRs/Ligand Complexes. 337-351 (2015).
26. Kelm, S., Shi, J. & Deane, C. M. MEDELLER: homology-based coordinate generation for membrane proteins. Bioinformatics 26, 2833-2840 (2010).
27. Rasmussen, S. G. F. et al. Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477, 549-555 (2011).
28. Kruse, A. C. et al. Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature 504, 101-106 (2013).
29. Huang, W. et al. Structural insights into-opioid receptor activation. Nature 524, 315-321 (2015).
30. Carpenter, B., Nehme, R., Warne, T., Leslie, A. G. W. & Tate, C. G. Structure of the adenosine A(2A) receptor bound to an engineered G protein. Nature 536, 104-107 (2016).
31. Bang, I. & Choi, H. J. Structural features of beta2 adrenergic receptor: crystal structures and beyond. Molecules and cells 38, 105-111 (2015).
32. Haga, K. et al. Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature 482, 547-551 (2012).
33. Borrelli, K. W., Vitalis, A., Alcantara, R. & Guallar, V. PELE: Protein energy landscape exploration. A novel Monte Carlo based technique. Journal of chemical theory and computation 1, 1304-1311 (2005).
34. Madadkar-Sobhani, A. & Guallar, V. PELE web server: atomistic study of biomolecular systems at your fingertips. Nucleic Acids Res 41, W322-W328 (2013).
35. Borrelli, K. W., Cossins, B. & Guallar, V. Exploring Hierarchical Refinement Techniques for Induced Fit Docking with Protein and Ligand Flexibility. Journal of Computational Chemistry 31, 1224-1235 (2010).
36. Katiyar, S. P., Jain, A., Dhanjal, J. K. & Sundar, D. Mixed Inhibition of cPEPCK by Genistein, Using an Extended Binding Site Located Adjacent to Its Catalytic Cleft. PLoS One 10, e0141987 (2015).
37. Ballesteros, J.A. & Weinstein, H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods in Neurosciences 25, 366-428 (1995).
38. Shoichet, B. K. & Kobilka, B. K. Structure-based drug screening for G-protein-coupled receptors. Trends in pharmacological sciences 33, 268-272 (2012).
39. Bermudez, M. & Wolber, G. Structure versus function-The impact of computational methods on the discovery of specific GPCR-ligands. Bioorg Med Chem 23, 3907-3912 (2015).
40. Schmidt, T., Bergner, A. & Schwede, T. Modelling three-dimensional protein structures for applications in drug design. Drug discovery today 19, 890-897 (2014).
41. Wiener, A., Shudler, M., Levit, A. & Niv, M. Y. BitterDB: a database of bitter compounds. Nucleic Acids Res 40, D413-419 (2012).
42. Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Molecular biology and evolution 30, 772-780 (2013).
43. Jacobson, M. P. et al. A hierarchical approach to all-atom protein loop prediction. Proteins 55, 351-367 (2004).
44. Jacobson, M. P., Friesner, R. A., Xiang, Z. & Honig, B. On the Role of the Crystal Environment in Determining Protein Side-chain Conformations. Journal of Molecular Biology 320, 597-608 (2002).
45. Fang, G., Weiser, B., Visosky, A., Moran, T. & Burger, H. PCR-mediated recombination: a general method applied to construct chimeric infectious molecular clones of plasma-derived HIV-1 RNA. Nat Med 5, 239-242 (1999).
46. Behrens, M. et al. Members of RTP and REEP gene families influence functional bitter taste receptor expression. J Biol Chem 281, 20650-20659 (2006).
47. Isberg, V. et al. GPCRdb: an information system for G protein-coupled receptors. Nucleic Acids Res 45, 2936 (2017).
48. Ballesteros, J.A. & Weinstein, H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods in Neurosciences 25, 366-428 (1995).