Binding of Glutamate to the Umami Receptor

J.J. López Cascales (1, 2) , S.D. Oliveira Costa (1) , Bert L. de Groot (3) , D. Eric Walters (3)

1 Bioinformatic and Macromolecules Group (BIOMAC)
2 and Department of Pharmaceutical Sciences
3 Computational biomolecular dynamics group

The umami taste receptor is a heterodimer composed of two members of the T1R taste receptor family: T1R1 and T1R3. It detects glutamate in humans, and is a more general amino acid detector in other species. We have constructed homology models of the ligand binding domains of the human umami receptor (based on crystallographic structures of the metabotropic glutamate receptor of the central nervous system). We have carried out molecular dynamics simulations of the ligand binding domains, and we find that the likely conformation is that in which T1R1 receptor protein exists in the closed conformation, and T1R3 receptor in the open conformation in the heterodimer. Further, we have identified the important binding interactions and have made an estimate of the relative free energies associated with the two glutamate binding sites.

Mots clés: Glutamate; umami; taste receptor; MD simulations

Domaines: Chimie-Physique [physics.chem-ph]

J.J. López Cascales, S.D. Oliveira Costa, Bert L. de Groot, D. Eric Walters. Binding of Glutamate to the Umami Receptor. Biophysical Chemistry, 2010, 152 (1-3), pp.139. ⟨10.1016/j.bpc.2010.09.001⟩. ⟨hal-00694294⟩