Human sweet taste receptors

Max M, Margolskee RE. Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. J. Biol. Chem. 2005 280 34296-34305. 33. 

Jiang, P., Cui, M., Zhao, B., Snyder, LA., Benard, L.M., Osman, R., Max, M., and Margolskee, R.F. (2005). Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. J. Biol. Chem. 280,34296-34305. 

Use of these programs is documented in a multitude of publications trying to predict biological activity of compounds modulating the human carbonic anhy-drase [9, 10], G protein-coupled receptors (GPCRs) [10, 13, 25, 27, 30, 31], varicella-zoster virus and human thymidine kinases [32], cytochrome P-450-depen-dent lanosterol 14a-demethylase (P45014DM) [33], a sweet taste receptor [34], / -tubulin [35], ion channels [28, 36, 37] and others. 

Morini G, Bassoli A, Temussi PA (2005) From small sweeteners to sweet proteins anatomy of the binding sites of the human T1R2 T1R3 receptor. J Med Chem 48 5520-5529 Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001) Mammalian sweet taste receptors. Cell 106 381-390... 

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 lab-dane diterpenoids, strychnine, and denatonium. J Agric Food Chem 55 6236-6243 Brouwer JN, Hellekant G, Kasahara Y, van der Wei H, Zotterman Y (1973) Electrophysiological study of the gustatory effects of the sweet proteins monellin and thaumatin in monkey, guinea pig and rat. Acta Physiol Scand 89 550-557... 

Just as in olfaction, a number of clues pointed to the involvement of G proteins and, hence, 7TM receptors in the detection of bitter and sweet tastes. The evidence included the isolation of a specific G protein a subunit termed gustducin, which is expressed primarily in taste buds (Figure 32.13). How could the 7TM receptors be identified The ability to detect some compounds depends on specific genetic loci in both human beings and mice. For instance, the ability to taste the bitter compound 6- -propyl-2-thiouracil (PROP) was mapped to a region on human chromosome 5 by comparing DNA markers of persons who vary in sensitivity to this compound. 

An experimental difficulty lies in the fact that there are only a few thousand taste buds in the tongue, with only 50-100 cells in a bud. They age rapidly, having a lifespan of only about ten days. There may be only 30,000-50,000 hard-to-isolate taste receptor cells on the tongue s surface. However, very recently published reports describe a large family of bitter and sweet receptors in mice and humans " and in Drosophilu The sweet-sour receptors are thought to activate a G protein called gustducin, which plays a role similar to that of transducin in vision and... 

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