Abstract
L-glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). Although just a few glutamate receptor ligands have turned out to be clinically useful, primarily because of unfavorable psychotropic side effects, the glutamate system remains an attractive molecular target in the treatment of epilepsy, neurodegenerative diseases (Alzheimers disease, Parkinsons disease, Huntingtons chorea), schizophrenia, ischemia, pain, alcoholism and mood disorders. Knowledge about the structure of ionotropic glutamate receptors (iGluRs) at atomic resolution is vital for the determination of their physiological and pathological importance and, thus, for drug design. Recently, tremendous progress has been made in structure elucidation and understanding of the functioning of iGluRs. The data about general topology and modular composition of iGluRs as well as numerous crystal structures of ligand binding domains of many iGluR subtypes has been supplemented with the first molecular models of the whole receptor protein, followed by the first crystal structures of N-terminal domains and finally by the first crystal structure of the whole tetrameric iGluR. This review summarizes experimental and computational efforts to determine iGluR molecular architecture and focus on the above listed achievements of the last years. In particular, the aspects of iGluR structure which are important for drug design, like the molecular characterstics of the ligand binding sites, are depicted in detail.
Keywords: NTD of ionotropic glutamate receptors, LBD of ionotropic glutamate receptors, glutamate ion channel, gating of glutamate ion channels, symmetry of ionotropic glutamate receptors
Current Medicinal Chemistry
Title: Molecular Structure of Ionotropic Glutamate Receptors
Volume: 17 Issue: 24
Author(s): A.A. Kaczor and D. Matosiuk
Affiliation:
Keywords: NTD of ionotropic glutamate receptors, LBD of ionotropic glutamate receptors, glutamate ion channel, gating of glutamate ion channels, symmetry of ionotropic glutamate receptors
Abstract: L-glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). Although just a few glutamate receptor ligands have turned out to be clinically useful, primarily because of unfavorable psychotropic side effects, the glutamate system remains an attractive molecular target in the treatment of epilepsy, neurodegenerative diseases (Alzheimers disease, Parkinsons disease, Huntingtons chorea), schizophrenia, ischemia, pain, alcoholism and mood disorders. Knowledge about the structure of ionotropic glutamate receptors (iGluRs) at atomic resolution is vital for the determination of their physiological and pathological importance and, thus, for drug design. Recently, tremendous progress has been made in structure elucidation and understanding of the functioning of iGluRs. The data about general topology and modular composition of iGluRs as well as numerous crystal structures of ligand binding domains of many iGluR subtypes has been supplemented with the first molecular models of the whole receptor protein, followed by the first crystal structures of N-terminal domains and finally by the first crystal structure of the whole tetrameric iGluR. This review summarizes experimental and computational efforts to determine iGluR molecular architecture and focus on the above listed achievements of the last years. In particular, the aspects of iGluR structure which are important for drug design, like the molecular characterstics of the ligand binding sites, are depicted in detail.
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Cite this article as:
Kaczor A.A. and Matosiuk D., Molecular Structure of Ionotropic Glutamate Receptors, Current Medicinal Chemistry 2010; 17 (24) . https://dx.doi.org/10.2174/092986710791859379
DOI https://dx.doi.org/10.2174/092986710791859379 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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