Quantum chemical study of agonist-receptor vibrational interactions for activation of the glutamate receptor

M. Kubo, K. Odai, T. Sugimoto, Etsuro Ito

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

To understand the mechanism of activation of a receptor by its agonist, the excitation and relaxation processes of the vibrational states of the receptor should be examined. As a first approach to this problem, we calculated the normal vibrational modes of agonists (glutamate and kainate) and an antagonist (6-cyano-7-nitroquinoxaline-2,3-dione: CNQX) of the glutamate receptor, and then investigated the vibrational interactions between kainate and the binding site of glutamate receptor subunit GluR2 by use of a semiempirical molecular orbital method (MOPAC2000-PM3). We found that two local vibrational modes of kainate, which were also observed in glutamate but not in CNQX, interacted through hydrogen bonds with the vibrational modes of GluR2: (i) the bending vibration of the amine group of kainate, interacting with the stretching vibration of the carboxyl group of Glu705 of GluR2, and (ii) the symmetric stretching vibration of the carboxyl group of kainate, interacting with the bending vibration of the guanidinium group of Arg485. We also found collective modes with low frequency at the binding site of GluR2 in the kainate-bound state. The vibrational energy supplied by an agonist may flow from the high-frequency local modes to the low-frequency collective modes in a receptor, resulting in receptor activation.

Original languageEnglish
Pages (from-to)869-874
Number of pages6
JournalJournal of Biochemistry
Volume129
Issue number6
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Kainic Acid
Glutamate Receptors
Chemical activation
Vibration
6-Cyano-7-nitroquinoxaline-2,3-dione
Stretching
Binding Sites
Excitatory Amino Acid Agonists
Excitatory Amino Acid Antagonists
Guanidine
Relaxation processes
Molecular orbitals
Amines
Glutamic Acid
Hydrogen
Hydrogen bonds

Keywords

  • Agonist-receptor vibrational interaction
  • Glutamate receptor
  • Kainate
  • Normal vibrational mode analysis
  • PM3 method

ASJC Scopus subject areas

  • Biochemistry

Cite this

Quantum chemical study of agonist-receptor vibrational interactions for activation of the glutamate receptor. / Kubo, M.; Odai, K.; Sugimoto, T.; Ito, Etsuro.

In: Journal of Biochemistry, Vol. 129, No. 6, 2001, p. 869-874.

Research output: Contribution to journalArticle

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