From small sweeteners to sweet proteins: Anatomy of the binding sites of the human T1R2_T1R3 receptor

Journal of Medicinal Chemistry

Volumn 48, Issue 17, 2005, Pages 5520-5529

  Morini, Gabriella ^a   Bassoli, Angela ^a   Temussi, Piero A ^b,c,d  

^a UNIVERSITY OF MILAN   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^c NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

^d ACCADEMIA NAZIONALE DEI LINCEI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CARBOHYDRATE; G PROTEIN COUPLED RECEPTOR; METABOTROPIC RECEPTOR 1; PEPTIDE; PROTEIN; PROTEIN T1R2; PROTEIN T1R3; SWEET PROTEIN; SWEETENING AGENT; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; LIGAND BINDING; RECEPTOR BINDING; SWEETNESS; TASTE BUD;

BINDING SITES; CARBOHYDRATES; HUMANS; LIGANDS; MODELS, MOLECULAR; MOLECULAR WEIGHT; PEPTIDES; PROTEIN STRUCTURE, TERTIARY; PROTEIN SUBUNITS; PROTEINS; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, METABOTROPIC GLUTAMATE; SWEETENING AGENTS; TASTE; THERMODYNAMICS;

EID: 23944498549     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0503345     Document Type: Article

References (43)

1. Pin, J. P.; Galvez, T.; Prezeau, L. Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol. Ther. 2003, 98, 325-354.
2. Max, M.; Shanker, Y. G.; Huang, L.; Rong, M.; Liu, Z.; Campagne, F.; Weinstein, H.; Damak, S.; Margolskee, R. F. Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat. Genet. 2001, 28, 58-63.
3. Montmayeur, J. P.; Liberles, S. D.; Matsunami, H.; Buck, L. B. A candidate taste receptor gene near a sweet taste locus. Nat. Neurosci. 2001, 4, 492-498.
4. Kitagawa, M.; Kusakabe, Y.; Miura, H.; Ninomiya, Y.; Hino, A. Molecular genetic identification of a candidate receptor gene for sweet taste. Biochem. Biophys. Res. Commun. 2001, 283, 236-242.
5. Li, X.; Inoue, M.; Reed, D. R.; Hunque, T.; Puchalski, R. B.; Tordoff, M. G.; Ninomiiya, Y.; Beauchamp, G. K.; Bachmanov, A. A. High-resolution genetic mapping of the saccharin preference locus (Sac) and the putative sweet taste receptor (T1R1) gene (Gpr70) to mouse distal Chromosome 4. Mamm. Genome 2001, 12, 13-16.
6. Sainz, E.; Korley, J. N.; Battey, J. F.; Sullivan, S. L. Identification of a novel member of the T1R family of putative taste receptors. J. Neurochem. 2001, 77, 896-903.
7. Li, X.; Staszewski, L.; Xu, H.; Durick, K.; Zoller, M.; Adler, E. Human receptors for sweet and umami taste. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4692-4696.
8. Ariyasu, T.; Matsumoto, S.; Kyono, F.; Hanaya, T.; Arai, S.; Ikeda, M.; Kurimoto M. Taste receptor T1R3 is an essential molecule for the cellular recognition of the disaccharide trehalose. In Vitro Cell. Dev. Biol.: Anim. 2003, 39, 80-88.
9. Xu, H.; Staszewski, L.; Tang, H.; Adler, E.; Zoller, M.; Li, X. Different functional roles of T1R subunits in the heteromeric taste receptors. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 14258-14263.
10. Schiffman, S. S. Receptors that mediate sweetness: inferences from biochemical, electrophysiological and psychophysical data. Pure Appl. Chem. 1997, 69, 701-708.
11. Litschig, S.; Gasparini, F.; Rueegg, D.; Munier, N.; Flor, P. J.; Vranesic, I.-T.; Prezeau, L.; Pin, J.-P.; Thomsen, C.; Kuhn, R. CPCCOEt, a noncompetitive mGluR1 antagonist, inhibits receptor signaling without affecting glutamate binding. Mol. Pharmacol. 1999, 55, 453-461.
12. Carroll, F. Y.; Stolle, A.; Beart, P. M.; Voerste, A.; Brabet, I.; Mauler, F.; Joly, C.; Antonicek, H.; Bockaert, J.; Mueller, T.; Pin, J. P.; Prezeau, L. BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity. Mol. Pharmacol. 2001, 59, 965-973.
13. Knoflach, F.; Mutel, V.; Jolidon, S.; Kew, J. N.; Malherbe, P.; Vieira, E.; Wichmann, J.; Kemp, J. A. Positive allosteric modulators of metabotropic glutamate 1 receptor: characterization, mechanism of action, and binding site. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 13402-13407.
14. Shallenberger, R. S.; Acree, T. Molecular theory of sweet taste. Nature 1967, 216, 480-482.
15. Kier, L. B. Molecular theory of sweet taste. J. Pharm. Sci. 1972, 61, 1394-1397.
16. Temussi, P. A.; Lelj, F.; Tancredi, T. Three-dimensional mapping of the sweet taste receptor site. J. Med. Chem. 1978, 21, 1154-1158.
17. Temussi, P. A.; Lelj, F.; Tancredi, T.; Castiglione-Morelli, M. A.; Pasture, A. Soft agonist-receptor interactions: theoretical and experimental simulation of the active site of the receptor site of sweet molecules. Int. J. Quantum Chem. 1984, 26, 889-906.
18. Temussi, P. A.; Lelj, F.; Tancredi, T. Structure-activity relationship of sweet molecules. In Sweeteners, discovery, molecular design and chemoreception; Walters, D. E., Orthofer, F. T., DuBois, G. E., Eds.; ACS Symposium Series 450; American Chemical Society: Washington, DC, 1991; pp 143-161.
19. Iwamura, H. Structure-sweetness relationship of L-aspartyl dipeptide analogues. A receptor site topology. J. Med. Chem. 1981, 24, 572-578.
20. Goodman, M.; Coddington, J.; Mierke, D. F. A model for the sweet taste of stereoisomeric retro-inverso and dipeptide amides. J. Am. Chem. Soc. 1987, 109, 4712-4714.
21. Tinti, J. M.; Nofre, C. Why does a sweetener taste sweet? A new model. In Sweeteners, discovery, molecular design and chemoreception; Walters, D. E., Orthofer, F. T., DuBois, G. E., Eds.; ACS Symposium Series 450; American Chemical Society: Washington, DC, 1991; pp 206-213.
22. Bassoli, A.; Drew, M. G. B.; Merlini, L.; Morini, G. A general pseudoreceptor model for sweet compounds: a semiquantitative prediction of binding affinity for sweet tasting molecules. J. Med. Chem. 2002, 45, 4402-4409.
23. Morris, J. A. Sweetening agents from natural sources. Lloydia 1976, 39, 25-38.
24. Tancredi, T.; Pastore, A.; Salvadori, S.; Esposito, V.; Temussi, P. A. Interaction of sweet proteins with their receptor. A conformational study of peptides corresponding to loops of brazzein, monellin and thaumatin. Eur. J. Biochem. 2004, 271, 2231-2240.
25. Temussi, P. A. Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin with the T1R2_T1R3 receptor. FEBS Lett. 2002, 526, 1-3.
26. Kunishima, N.; Shimada, Y.; Tsuji, Y.; Sato, T.; Yamamoto, M.; Kumasaka, T.; Nakanishi, S.; Jingami, H.; Morikawa, K. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 2000, 407, 971-977.
27. 3+. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 2660-2665.
28. Morini, G.; Temussi, P. A. Micro and macro models of the sweet receptor. Chem. Sens. 2005, 30, 86-87.
29. Vedani, A.; Zbinden, P.; Snyder, J. P.; Greenidge, P. A. Pseudoreceptor modelling: the construction of three-dimensional receptor surrogates. J. Am. Chem. Soc. 1995, 117, 4987-4994.
30. Hatada, M.; Jancarik, J.; Graves, B.; Kim, S.-H. Crystal structure of aspartame, a peptide sweetener. J. Am. Chem. Soc. 1985, 107, 4279-4282.
31. Yamazaki, T.; Benedetti, E.; Kent, D.; Goodman, M. Conformational Requirements for Sweet-Tasting Peptides and Peptidomimetics. Angew. Chem., Int. Ed. Engl. 1994, 33, 1437-1451.
32. Kamphuis, J.; Lelj, F.; Tancredi, T.; Toniolo, C.; Temussi, P. A. SAR of Sweet Molecules: Conformational Analysis of Two Hypersweet and Two Conformationally Restricted Aspartame Analogues. QSAR 1992, 11, 486-491.
33. Polinelli, S.; Broxterman, Q. B.; Schoemaker, H. E.; Boesten, W. H. J.; Crisma, M.; Valle, G.; Toniolo, C.; Kamphuis, J. New aspartame-like sweeteners containing L-(α-Me)Phe. Bioorg. Med. Chem. Lett. 1992, 2, 453-456.
34. Walters, D. E. Homology-based model of the extracellular domain of the taste receptor T1R3. Pure Appl. Chem. 2002, 74, 1117-1123.
35. DuBois, G. E. Unraveling the biochemistry of sweet and umami tastes. Proc. Natl Acad. Sci. U.S.A. 2004, 101, 13972-13973.
36. Thompson, J. D.; Higgins, D. G.; Gibson, T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment trough sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994, 22, 4673-4680.
37. Peitsch, M. C. ProMod and Swiss-Model: Internet-based tools for automated comparative protein modelling. Biochem. Soc. Trans. 1996, 24, 274-279.
38. Peitsch, M. C. Protein modelling by E-Mail. Bio/Technology 1995, 13, 658-660.
39. Guex, N.; Peitsch, M. C. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modelling. Electrophoresis 1997, 18, 2714-2723.
40. Vakser, I. A. Protein docking for low-resolution structures. Protein Eng. 1995, 8, 371-377.
41. Vakser, I. A.; Matar, O. G.; Lam C. F. A systematic study of low-resolution recognition in protein-protein complexes. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 8477-8482.
42. Koradi, R.; Billeter, M.; Wüthrich, K. MOLMOL: a program for display and analysis of macromolecular structure. J. Mol. Graphics 1996, 14, 51-55.
43. InsightII, Version 97.0; Molecular Simulations Inc.: San Diego, CA, 1997.