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Computational Studies of Ligand-Receptor Interactions in Ionotropic Glutamate Receptors

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Molecular Neuropharmacology

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Abstract

The determination by Gouaux and co-workers of the three-dimensional (3D) structure of a construct corresponding to the ligand-binding domain (S1S2) of the iGluR2 ionotropic glutamate receptor subunit constitutes a breakthrough in glutamate receptor research. Since the first publication of an iGluR2 construct (S1S2I) in complex with kainate (1), a number of X-ray structures based on a slightly modified construct (S1S2J) have been reported, including the ligand-free apo form of the protein (2) and ligand—iGlur2 complexes involving antagonists as well as agonists. The ligands in these complexes include the agonists (S)-glutamate (Glu) (2), (S)-2-amino-3-hydroxy-5-methyl-4-isoxazolyl propionic acid (AMPA) (2), kainate (2), (S)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)-propionic acid (ACPA), (3), (S)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid (2-methyltetrazolyl AMPA) (3), (S)-2-amino-3-(4-bromo-3-hydroxy-5-isoxazolyl) propionic acid (Br-HIBO) (3); and the competitive antagonists 6,7-dinitro-2,3-quinoxalinedione (DNQX) (2) and (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]-propionic acid (ATPO) (4). The structures of these ligands are shown in Fig. 1.

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Authors
  1. Jeremy R. Greenwood
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  2. Tommy Liljefors
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Editors and Affiliations

  1. Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark

    Arne Schousboe PhD, DSc

  2. Department of Medical Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark

    Hans Bräuner-Osborne PhD, DSc

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Greenwood, J.R., Liljefors, T. (2004). Computational Studies of Ligand-Receptor Interactions in Ionotropic Glutamate Receptors. In: Schousboe, A., Bräuner-Osborne, H. (eds) Molecular Neuropharmacology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-672-0_1

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  • DOI: https://doi.org/10.1007/978-1-59259-672-0_1

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-384-8

  • Online ISBN: 978-1-59259-672-0

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