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: FEBS Journal, Vol. 279, No. 17, 01.09.2012, p. 3112-3120.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Mouritsen, OG & Khandelia, H 2012, 'Molecular mechanism of the allosteric enhancement of the umami taste sensation', FEBS Journal, vol. 279, no. 17, pp. 3112-3120. https://doi.org/10.1111/j.1742-4658.2012.08690.x

APA

Mouritsen, O. G., & Khandelia, H. (2012). Molecular mechanism of the allosteric enhancement of the umami taste sensation. FEBS Journal, 279(17), 3112-3120. https://doi.org/10.1111/j.1742-4658.2012.08690.x

Vancouver

Mouritsen OG, Khandelia H. Molecular mechanism of the allosteric enhancement of the umami taste sensation. FEBS Journal. 2012 Sep 1;279(17):3112-3120. https://doi.org/10.1111/j.1742-4658.2012.08690.x

Author

Mouritsen, Ole G. ; Khandelia, Himanshu. / Molecular mechanism of the allosteric enhancement of the umami taste sensation. In: FEBS Journal. 2012 ; Vol. 279, No. 17. pp. 3112-3120.

Bibtex

@article{654f51420670401ead7f87d608a581bc,
title = "Molecular mechanism of the allosteric enhancement of the umami taste sensation",
abstract = "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.",
keywords = "allosteric mechanism, GPCR, molecular dynamics, T1R1/T1R3, umami taste receptor",
author = "Mouritsen, {Ole G.} and Himanshu Khandelia",
year = "2012",
month = "9",
day = "1",
doi = "10.1111/j.1742-4658.2012.08690.x",
language = "English",
volume = "279",
pages = "3112--3120",
journal = "F E B S Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "17",

}

RIS

TY - JOUR

T1 - Molecular mechanism of the allosteric enhancement of the umami taste sensation

AU - Mouritsen, Ole G.

AU - Khandelia, Himanshu

PY - 2012/9/1

Y1 - 2012/9/1

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

UR - http://www.scopus.com/inward/record.url?scp=84865234816&partnerID=8YFLogxK

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