Quantum chemical study of agonist-receptor vibrational interactions for activation of the glutamate receptor.
Quantum chemical study of agonist-receptor vibrational interactions for activation of the glutamate receptor.
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激活谷氨酸受体的激动剂-受体振动相互作用的量子化学研究。
DOI：
10.1093/oxfordjournals.jbchem.a002931
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发表时间：
2001
影响因子：
2.7
通讯作者：
E. Ito
中科院分区：
文献类型：
--
作者：
M. Kubo;K. Odai;T. Sugimoto;E. Ito
为了了解受体激动剂激活受体的机制，应该研究受体振动状态的激发和松弛过程。作为解决这个问题的第一种方法，我们计算了谷氨酸受体激动剂(谷氨酸和红藻氨酸)和拮抗剂(6-氰基-7-硝基喹恶啉-2，3-二酮：CNQX)的正常振动模式，然后用半经验分子轨道方法(MOPAC2000-PM3)研究了红藻氨酸与谷氨酸受体亚单位GluR2结合部位的振动相互作用。我们发现，在谷氨酸中也观察到了红藻氨酸的两个局域振动模式，但在CNQX中没有观察到，它们通过氢键与GluR2的振动模式相互作用：(I)红藻氨酸的氨基的弯曲振动，与GluR2的Glu705的伸缩振动相互作用；(Ii)红藻氨酸的羧基的对称伸缩振动，与Arg485的胍基的弯曲振动相互作用。我们还在海人藻酸结合态的GluR2结合部位发现了低频率的集体模式。激动剂提供的振动能量可能从受体中的高频局部模式流向低频集体模式，导致受体激活。
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.