Abstract
Two X-ray structures of the GluR2 ligand-binding core in complex with (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid ((S)-ATPA) have been determined with and without Zn(2+) ions. (S)-ATPA induces a domain closure of ca. 21 degrees compared to the apo form. The tert-butyl moiety of (S)-ATPA is buried in a partially hydrophobic pocket and forces the ligand into the glutamate-like binding mode. The structures provide new insight into the molecular basis of agonist selectivity between AMPA and kainate receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Crystallography, X-Ray
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Dimerization
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Excitatory Amino Acid Agonists / chemistry*
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Isoxazoles / chemistry*
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Ligands
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Models, Molecular
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Propionates / chemistry*
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Protein Conformation
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Protein Subunits
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Receptors, AMPA / agonists
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Receptors, AMPA / chemistry*
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Stereoisomerism
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Zinc / chemistry
Substances
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Excitatory Amino Acid Agonists
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Isoxazoles
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Ligands
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Propionates
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Protein Subunits
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Receptors, AMPA
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alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate
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Zinc
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glutamate receptor ionotropic, AMPA 2