Characterization of the binding site of aspartame in the human sweet taste receptor

Chemical Senses

Volumn 40, Issue 8, 2015, Pages 577-586

  Maillet, Emeline L ^a   Cui, Meng ^a   Jiang, Peihua ^a,b   Mezei, Mihaly ^a   Hecht, Elizabeth ^a   Quijada, Jeniffer ^a   Margolskee, Robert F ^a,b   Osman, Roman ^a   Max, Marianna ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b MONELL CHEMICAL SENSES CENTER   (United States)

Author keywords

Aspartame; Cyclamate; Homology modeling; Site directed mutagenesis; Sweet taste receptor

Indexed keywords

ASPARTAME; G PROTEIN COUPLED RECEPTOR; SWEET TASTE RECEPTOR; T1R2 PROTEIN; T1R3 PROTEIN; UNCLASSIFIED DRUG; PROTEIN BINDING; SWEETENING AGENT; TASTE RECEPTORS, TYPE 1;

ARTICLE; BINDING SITE; CONTROLLED STUDY; EMBRYO; HUMAN; HUMAN CELL; HYDROGEN BOND; HYDROPHOBICITY; MOLECULAR DOCKING; MOLECULAR DYNAMICS; PREDICTION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN STRUCTURE; RESIDUE ANALYSIS; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS; ANIMAL; CHEMICAL PHENOMENA; CHEMISTRY; DIMERIZATION; GENETICS; HEK293 CELL LINE; METABOLISM; MOUSE; PHYSIOLOGY; PROTEIN QUATERNARY STRUCTURE; SITE DIRECTED MUTAGENESIS; TASTE;

ANIMALS; ASPARTAME; BINDING SITES; DIMERIZATION; HEK293 CELLS; HUMANS; HYDROGEN BONDING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; MICE; MOLECULAR DOCKING SIMULATION; MUTAGENESIS, SITE-DIRECTED; PROTEIN BINDING; PROTEIN STRUCTURE, QUATERNARY; RECEPTORS, G-PROTEIN-COUPLED; SWEETENING AGENTS; TASTE;

EID: 84943768862     PISSN: 0379864X     EISSN: 14643553     Source Type: Journal    
DOI: 10.1093/chemse/bjv045     Document Type: Article

References (49)

1. Amrein H, Bray S. 2003. Bitter-sweet solution in taste transduction. Cell. 112(3):283-284.
2. Assadi-Porter FM, Maillet EL, Radek JT, Quijada J, Markley JL, Max M. 2010. Key amino acid residues involved in multi-point binding interactions between brazzein, a sweet protein, and the T1R2-T1R3 human sweet receptor. J Mol Biol. 398:584-599.
3. Avena NM, Rada P, Hoebel BG. 2008. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 32:20-39.
4. Bachmanov AA, Tordoff MG, Beauchamp GK. 2001. Sweetener preference of C57BL/6ByJ and 129P3/J mice. Chem Sens. 26:905-913.
5. Bowie JU, Luthy R, Eisenberg D. 1991. A method to identify protein sequences that fold into a known 3-dimensional structure. Science. 253:164-170.
6. Breneman CM, Wiberg KB. 1990. Determining atom-centered monopoles from molecular electrostatic potentials-the need for high sampling density in formamide conformational-analysis. J Comput Chem. 11:361-373.
7. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M. 1983. CHARMM-a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem. 4:187-217.
8. Cui M, Jiang PH, Maillet E, Max M, Margolskee RF, Osman R. 2006. The heterodimeric sweet taste receptor has multiple potential ligand binding sites. Curr Pharm Des. 12:4591-4600.
9. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Zakrzewski VG, Montgomery JA, Stratmann J, Burant JC, et al. 2002. Gaussian 98. Pittsburgh, PA: Gaussian, Inc.
10. Goodsell DS, Morris GM, Olson AJ. 1996. Automated docking of flexible ligands: applications of AutoDock. J Mol Recognit. 9:1-5.
11. Goudet C, Kniazeff J, Hlavackova V, Malhaire F, Maurel D, Acher F, Blahos J, Prezeau L, Pin JP. 2005. Asymmetric functioning of dimeric metabotropic glutamate receptors disclosed by positive allosteric modulators. J Biol Chem. 280:24380-24385.
12. Heyer BR, Taylor-Burds CC, Mitzelfelt JD, Delay ER. 2004. Monosodium glutamate and sweet taste: discrimination between the tastes of sweet stimuli and glutamate in rats. Chem Senses. 29:721-729.
13. Jiang P, Cui M, Ji Q, Snyder L, Liu Z, Benard L, Margolskee RF, Osman R, Max M. 2005a. Molecular mechanisms of sweet receptor function. Chem Sens. 30:I17-I18.
14. Jiang PH, Cui M, Zhao BH, Liu Z, Snyder LA, Benard LMJ, Osman R, Margolskee RF, Max M. 2005b. Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. J Biol Chem. 280:15238-15246.
15. Jiang PH, Cui M, Zhao BH, Snyder LA, Benard LMJ, Osman R, Max M, Margolskee RF. 2005c. Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. J Biol Chem. 280:34296-34305.
16. Jiang PH, Ji QZ, Liu Z, Snyder LA, Benard LMJ, Margolskee RF, Max M. 2004. The cysteine-rich region of T1R3 determines responses to intensely sweet proteins. J Biol Chem. 279:45068-45075.
17. Jingami H, Nakanishi S, Morikawa K. 2003. Structure of the metabotropic glutamate receptor. Curr Opin Neurobiol. 13:271-278.
18. Kitagawa M, Kusakabe Y, Miura H, Ninomiya Y, Hino A. 2001. Molecular genetic identification of a candidate receptor gene for sweet taste. Biochem Biophys Res Commun. 283:236-242.
19. Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K. 2000. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature. 407:971-977.
20. Li XD, Staszewski L, Xu H, Durick K, Zoller M, Adler E. 2002. Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A. 99:4692-4696.
21. Lindemann B. 1996. Taste reception. Physiol Rev. 76:719-766.
22. Liu B, Ha M, Meng XY, Kaur T, Khaleduzzaman M, Zhang Z, Jiang P, Li X, Cui M. 2011. Molecular mechanism of species-dependent sweet taste toward artificial sweeteners. J Neurosci. 31:11070-11076.
23. Luthy R, Bowie JU, Eisenberg D. 1992. Assessment of protein models with 3-dimensional profiles. Nature. 356:83-85.
24. Margolskee RF. 2002. Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem. 277:1-4.
25. Marti-Renom MA, Stuart AC, Fiser A, Sanchez R, Melo F, Sali A. 2000. Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct. 29:291-325.
26. Masuda K, Koizumi A, Nakajima K, Tanaka T, Abe K, Misaka T, Ishiguro M. 2012. Characterization of the modes of binding between human sweet taste receptor and low-molecular-weight sweet compounds. PLoS One. 7:e35380.
27. Max M, Shanker YG, Huang LQ, Rong M, Liu Z, Campagne F, Weinstein H, Damak S, Margolskee RF. 2001. Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat Genet. 28:58-63.
28. Mazur RH, Schlatte J, Goldkamp AH. 1969. Structure-taste relationships of some dipeptides. J Am Chem Soc. 91:2684-2691.
29. McDonald IK, Thornton JM. 1994. Satisfying hydrogen-bonding potential in proteins. J Mol Biol. 238:777-793.
30. Meguro T, Kashiwagi T, Satow Y. 2000. Crystal structure of the low-humidity form of aspartame sweetener. J Pept Res. 56:97-104.
31. Montmayeur JP, Liberles SD, Matsunami H, Buck LB. 2001. A candidate taste receptor gene near a sweet taste locus. Nat Neurosci. 4:492-498.
32. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ. 1998. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 19:1639-1662.
33. Muto T, Tsuchiya D, Morikawa K, Jingami H. 2007. Structures of the extracellular regions of the group II/III metabotropic glutamate receptors. Proc Natl Acad Sci U S A. 104:3759-3764.
34. Nelson G, Hoon MA, Chandrashekar J, Zhang YF, Ryba NJP, Zuker CS. 2001. Mammalian sweet taste receptors. Cell. 106:381-390.
35. Pin JP, Galvez T, Prezeau L. 2003. Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol Ther. 98:325-354.
36. Sali A, Blundell TL. 1993. Comparative protein modeling by satisfaction of spatial restraints. J Mol Biol. 234:779-815.
37. Schiffman SS, Booth BJ, Sattely-Miller EA, Graham BG, Gibes KM. 1999. Selective inhibition of sweetness by the sodium salt of +/- 2-(4-methoxyphenoxy) propanoic acid. Chem Sens. 24:439-447.
38. Sclafani A, Abrams M. 1986. Rats show only a weak preference for the artificial sweetener aspartame. Physiol Behav. 37:253-256.
39. Sclafani A, Perez C. 1997. Cypha(TM) propionic acid, 2-(4-methoxyphenol) salt inhibits sweet taste in humans, but not in rats. Physiol Behav. 61:25-29.
40. Slack JP. 2009. Functional method to identify tastants. US patent application US 12/297,695.
41. Thompson JD, Higgins DG, Gibson TJ. 1994. Clustal-W-improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22:4673-4680.
42. Tsuchiya D, Kunishima N, Kamiya N, Jingami H, Morikawa K. 2002. Structural views of the ligand-binding cores of a metabotropic glutamate receptor complexed with an antagonist and both glutamate and Gd3+. Proc Natl Acad Sci U S A. 99:2660-2665.
43. Ueda T, Ugawa S, Yamamura H, Imaizumi Y, Shimada S. 2003. Functional interaction between T2R taste receptors and G-protein alpha subunits expressed in taste receptor cells. J Neurosci. 23:7376-7380.
44. Wagner MW. 1971. Comparative rodent preferences for artificial sweeteners. J Comp Physiol Psychol. 75:483-490.
45. Wallace AC, Laskowski RA, Thornton JM. 1995. LIGPLOT-a program to generate schematic diagrams of protein ligand interactions. Protein Eng. 8:127-134.
46. Winnig M, Bufe B, Meyerhof W. 2005. Valine 738 and lysine 735 in the fifth transmembrane domain of rTas1r3 mediate insensitivity towards lactisole of the rat sweet taste receptor. BMC Neurosci. 6:22.
47. Xu H, Staszewski L, Tang H, Adler E, Zoller M, Li X. 2004. Different functional roles of T1R subunits in the heteromeric taste receptors. Proc Natl Acad Sci U S A. 101:14258-14263.
48. Zhang F, Klebansky B, Fine RM, Liu HT, Xu H, Servant G, Zoller M, Tachdjian C, Li XD. 2010. Molecular mechanism of the sweet taste enhancers. Proc Natl Acad Sci U S A. 107:4752-4757.
49. Zhao GQ, Zhang YF, Hoon MA, Chandrashekar J, Erlenbach I, Ryba NJP, Zuker CS. 2003. The receptors for mammalian sweet and umami taste. Cell. 115:255-266.