Mechanism of stabilization of the closed conformation of the umami receptor VFTM by IMP (green). Mechanism of stabilization of the closed conformation of the umami receptor VFTM by IMP (green). Whereas glutamate (golden) closes the two lobes by binding deep inside the VFTM near its hinge region (right), IMP further stabilizes the closed conformation by binding to the two lobes near the flytrap opening to the left. Because the upper (top) and lower (bottom) lobes are too far apart in the open conformation, IMP cannot activate the receptor by binding to one lobe in the absence of glutamate. Key residues for glutamate binding are blue, for IMP binding red. The two sweet taste enhancers SE2 and SE3 (Table 1) have been shown to act in a similar way at the sweet taste receptor. [Reproduced from Zhang F, Klebansky B, Fine RM, Xu H, Pronin A, Liu H, Tachdjian C, and Li X (2008a) Molecular mechanism for the umami taste synergism. Proc Natl Acad Sci USA105:20930–20934. Copyright © 2008 National Academy of Sciences U.S.A. Used with permission.] Stephan Urwyler Pharmacol Rev 2011;63:59-126 © 2011 by The American Society for Pharmacology and Experimental Therapeutics