ArticleBiochemistry2008
Chemical interplay in the mechanism of partial agonist activation in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Partial agonism in heteromeric GLUK2/GLUK5 kainate receptor.Proteins · 2025Article
- Structural dynamics of the glycine-binding domain of the N-methyl-D-aspartate receptor.The Journal of biological chemistry · 2015Article
- Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2.PloS one · 2015Article
- Role of conformational dynamics in α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor partial agonism.The Journal of biological chemistry · 2012Article
- Conformational changes at the agonist binding domain of the N-methyl-D-aspartic acid receptor.The Journal of biological chemistry · 2011Article
- Subunit arrangement in N-methyl-D-aspartate (NMDA) receptors.The Journal of biological chemistry · 2010Article
- Vibrational spectroscopic investigation of the ligand binding domain of kainate receptors.Protein science : a publication of the Protein Society · 2009Article
- Mechanism of partial agonism at the GluR2 AMPA receptor: Measurements of lobe orientation in solution.Biochemistry · 2008Article
- Luminescence resonance energy transfer investigation of conformational changes in the ligand binding domain of a kainate receptor.The Journal of biological chemistry · 2008Article
- LRET investigations of conformational changes in the ligand binding domain of a functional AMPA receptor.Biochemistry · 2008Article
- NMR spectroscopy of the ligand-binding core of ionotropic glutamate receptor 2 bound to 5-substituted willardiine partial agonists.Journal of molecular biology · 2008Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, one subtype in the family of ionotropic glutamate receptors, are the main receptors responsible for excitatory signaling in the mammalian central nervous system. Previous studies utilitizing the isolated ligand binding domain of these receptors have provided insight into the role of specific ligand-protein interactions in mediating receptor activation. However, these studies relied heavily on the partial agonist kainate, in which the alpha-amine group is constrained in a pyrrolidine ring. Here we have studied a series of substituted and unsubstituted willardiines with primary alpha-amine groups similar to that of the full agonist glutamate whose activation can be varied depending on the size of the substituent. The specific ligand-protein interactions in the mechanism of partial agonism in this subtype were investigated using vibrational spectroscopy, and the large-scale conformational changes in the ligand binding domain were studied with fluorescence resonance energy transfer (FRET). These investigations show that the strength of the interaction at the alpha-amine group correlates with the extent of cleft closure and extent of activation, with the agonist of higher efficacy showing larger cleft closure and stronger interactions at this group, suggesting that this is one of the mechanisms by which the agonist controls receptor activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.