NEWS OF THE WEEK S W E E T BONDAGE Model shows how the sweetener aspartame binds to a site on the sweetness receptor's T1R3 subunit. Red and blue are hydrogenbond donor and acceptor residues, respectively; aspartame is in gold, except for its carboxylate (red) and ammonium (blue) groups. Model prepared with MOLMOL U Mol. Graphics 1996p 74, 51).
HOMELAND
BIOCHEMISTRY
MAKING SENSE OF SWEETNESS Study explains a range of observations on effects of different sweeteners
A
MONG THE FIVE SENSES,
taste is probably the least understood. A new model of the human sweet-taste receptor now explains why diverse molecules, large and small, taste sweet and why sweet tastes are often additive. The model was created by chemistry professor Piero A. Temussi of the University of Naples and coworkers g. Med. Chem. 2005, 48,5520). If confirmed, it could aid the rational design of new sweeteners and lead to better treatments for diseases linked to sugar consumption (such as diabetes and obesity). For decades, most researchers believed there had to be multiple receptors for sweet taste, comments professor of biochemistry
and molecular biology D. Eric Walters of Rosalind Franklin University of Medicine & Science, North Chicago, a specialist in computer modeling and sweettaste transduction. "Sugars, amino acids, peptides, proteins, terpenes, heterocycles like saccharin, sulfamic acids, ureas, guanidines, and dozens of other classes of compounds taste sweet, and it was hard to envision any single binding site that could interact with all of them." The new study "suggests away in which these results can be rationalized—{through} different binding sites on the receptor," Walters says. 'The model is sufficiently detailed that you can now devise experiments to test the proposed sites. Ifou can do specific mutations ofresidues implicated by the model and see whether receptor binding is affected." A group based at Senomyx, a
flavorings biotech company in La Jolla, Calif., reported earlier that the perception of sweetness depends totally on the heterodimeric G-protein-coupled receptor (GPCR)T1R2-T1R3, suggesting that it was the sole sweet-taste receptor. Temussi and coworkers have nowmodeledTlR2TlR3 by comparing it with the glutamate receptor, a better understood GPCR of similar sequence, and have calculated the way sweeteners bind to the receptor. The model reveals four binding sites that can be occupied independently. Small-molecule sweeteners bind to an extracellular pocket on each of the subunits or a site on the receptor's transmembrane domain, and sweet proteins can bind to a "wedge site" above one of the pockets. "Our model incorporates all previous hypotheses formulated on the basis of the comparison of sweet compounds and explains why sweet taste can be elicited by substances as diverse as low-molecular-weight sweeteners, such as sugars and saccharin, and large sweet proteins, like monellin or thaumatin,"Temussi says. Because sweeteners can bind independently, the model also explains how sweet tastes can be additive, Temussi says.—STL) BORMAN
SECURITY
Manhattan Experiments Track Gases For Terror Response
L
ast Monday, scientists from several government agencies released two tracer gases in a 2-km 2 area of midtown Manhattan. In a series of experiments, they are tracking how harmful gases or particles might disperse through street canyons, subway tunnels, and buildings. Dubbed the Urban Dispersion Project, this Department of Homeland Security-sponsored effort aims to produce a computer model of airflow patterns that could help state and local officials better respond to an emergency or to a biological or chemical terrorist act. On six days over a three-week period ending Aug. 26, sulfur hexafluoride and
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C&EN / AUGUST
15,
2005
perfluorocarbons are to be released from three open-air sites within the designated area. Some 200 samplers will monitor the gases as they ride the wind. The monitors are positioned on streetlight poles, on rooftops, on subway platforms, and within an office building. In addition, 15 to 20 people equipped with personal sampling devices will walk the affected streets to monitor inhaled concentrations. Samples collected from perfluorocarbon monitors will be taken to Brookhaven National Lab for analysis by gas chromatography, while those for sulfur hexafluoride will go to a National Océanographie & Atmospheric Administration lab
at Idaho Falls, Idaho, also for GC studies. This August exercise follows an earlier round of testing that took place in midtown last March that discovered that wind patterns are best determined by equipment on rooftops, not at street level. A third run, with tracer gases being released in a subway, is slated for next spring. Lead scientist K. Jerry Allwine, an engineer from Pacific Northwest National Lab, says the aim of these field exercises "is to get real-time data on how something moves through and around midtown. The data are then used to validate and improve computer models for planning purposes and for emergency response."—LOIS EMBER
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