Comparative modeling of GABAA receptors:: Limits, insights, future developments

被引：124

作者：

Ernst, M

Brauchart, D

Boresch, S

Sieghart, W

机构：

[1] Univ Vienna, Inst Brain Res, Dept Biochem & Mol Biol, A-1090 Vienna, Austria

[2] Inst Theoret Chem & Struct Biol, A-1090 Vienna, Austria

来源：

NEUROSCIENCE | 2003年 / 119卷 / 04期

基金：

奥地利科学基金会;

关键词：

GABA(A) receptor structure; comparative (homology) modeling; acetylcholine binding protein; agonist binding; benzodiazepine binding; allosteric motions;

D O I：

10.1016/S0306-4522(03)00288-4

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

GABA(A) receptors are chloride ion channels that mediate fast synaptic transmission and belong to a superfamily of pentameric ligand-gated ion channels. The recently published crystal structure of the acetylcholine binding protein can be used as a template for comparative modeling of the extracellular domain of GABA(A) receptors. In this commentary, difficulties with comparative modeling at low sequence identity are discussed, the degree of structural conservation to be expected within the superfamily is analyzed and numerical estimates of model uncertainties in functional regions are provided. Topography of the binding sites at subunit-interfaces is examined and possible targets for rational mutagenesis studies are suggested. Allosteric motions are considered and a mechanism for mediation of positive cooperativity at the benzodiazepine site is proposed. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.

引用

页码：933 / 943

页数：11

共 63 条

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