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

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.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Kubo M,Odai K,Sugimoto T,Ito E

doi

10.1093/oxfordjournals.jbchem.a002931

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

869-74

issue

6

eissn

0021-924X

issn

1756-2651

journal_volume

129

pub_type

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