Molecular mechanism of the allosteric enhancement of the umami taste sensation
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Molecular mechanism of the allosteric enhancement of the umami taste sensation. / Mouritsen, Ole G.; Khandelia, Himanshu.
In: F E B S Journal, Vol. 279, No. 17, 2012, p. 3112-3120.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular mechanism of the allosteric enhancement of the umami taste sensation
AU - Mouritsen, Ole G.
AU - Khandelia, Himanshu
PY - 2012
Y1 - 2012
N2 - The fifth taste quality, umami, arises from binding of glutamate to the umami receptor T1R1/T1R3. The umami taste is enhanced several-fold upon addition of free nucleotides such as guanosine-5′-monophosphate (GMP) to glutamate-containing food. GMP may operate via binding to the ligand-binding domain of the T1R1 part of the umami receptor at an allosteric site. Using molecular dynamics simulations, we show that GMP can stabilize the closed (active) state of T1R1 by binding to the outer vestibule of the so-called Venus flytrap domain of the receptor. The transition between the closed and open conformations was accessed in the simulations. Using principal component analysis, we show that the dynamics of the Venus flytrap domain along the hinge-bending motion that activates signaling is dampened significantly upon binding of glutamate, and further slows down upon binding of GMP at an allosteric site, thus suggesting a molecular mechanism of cooperativity between GMP and glutamate.
AB - The fifth taste quality, umami, arises from binding of glutamate to the umami receptor T1R1/T1R3. The umami taste is enhanced several-fold upon addition of free nucleotides such as guanosine-5′-monophosphate (GMP) to glutamate-containing food. GMP may operate via binding to the ligand-binding domain of the T1R1 part of the umami receptor at an allosteric site. Using molecular dynamics simulations, we show that GMP can stabilize the closed (active) state of T1R1 by binding to the outer vestibule of the so-called Venus flytrap domain of the receptor. The transition between the closed and open conformations was accessed in the simulations. Using principal component analysis, we show that the dynamics of the Venus flytrap domain along the hinge-bending motion that activates signaling is dampened significantly upon binding of glutamate, and further slows down upon binding of GMP at an allosteric site, thus suggesting a molecular mechanism of cooperativity between GMP and glutamate.
KW - allosteric mechanism
KW - GPCR
KW - molecular dynamics
KW - T1R1/T1R3
KW - umami taste receptor
U2 - 10.1111/j.1742-4658.2012.08690.x
DO - 10.1111/j.1742-4658.2012.08690.x
M3 - Journal article
C2 - 22764741
AN - SCOPUS:84865234816
VL - 279
SP - 3112
EP - 3120
JO - F E B S Journal
JF - F E B S Journal
SN - 1742-464X
IS - 17
ER -
ID: 230975141