ArticleJournal of molecular biology2008
NMR spectroscopy of the ligand-binding core of ionotropic glutamate receptor 2 bound to 5-substituted willardiine partial agonists.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- ATP-competitive inhibitors modulate the substrate binding cooperativity of a kinase by altering its conformational entropy.Science advances · 2022Article
- Measurements of the Timescale and Conformational Space of AMPA Receptor Desensitization.Biophysical journal · 2020Article
- Mechanism of partial agonism in AMPA-type glutamate receptors.Nature communications · 2017Article
- Dysfunctional conformational dynamics of protein kinase A induced by a lethal mutant of phospholamban hinder phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Structural dynamics of the glycine-binding domain of the N-methyl-D-aspartate receptor.The Journal of biological chemistry · 2015Article
- Retour aux sources: defining the structural basis of glutamate receptor activation.The Journal of physiology · 2015Review
- Thermodynamics and mechanism of the interaction of willardiine partial agonists with a glutamate receptor: implications for drug development.Biochemistry · 2014Article
- Dynamics of cleft closure of the GluA2 ligand-binding domain in the presence of full and partial agonists revealed by hydrogen-deuterium exchange.The Journal of biological chemistry · 2013Article
- Article
- Role of conformational dynamics in α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor partial agonism.The Journal of biological chemistry · 2012Article
- Emerging models of glutamate receptor ion channel structure and function.Structure (London, England : 1993) · 2011Review
- Mechanism of AMPA receptor activation by partial agonists: disulfide trapping of closed lobe conformations.The Journal of biological chemistry · 2011Article
- Mechanisms of modal activation of GluA3 receptors.Molecular pharmacology · 2011Article
- Conformational changes at the agonist binding domain of the N-methyl-D-aspartic acid receptor.The Journal of biological chemistry · 2011Article
- Dynamically committed, uncommitted, and quenched states encoded in protein kinase A revealed by NMR spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Dynamics connect substrate recognition to catalysis in protein kinase A.Nature chemical biology · 2010Article
- Characterizing single-channel behavior of GluA3 receptors.Biophysical journal · 2010Article
- On the mechanisms of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor binding to glutamate and kainate.The Journal of biological chemistry · 2010Article
- Hydrophobic side chain dynamics of a glutamate receptor ligand binding domain.The Journal of biological chemistry · 2010Article
- Mechanisms of antagonism of the GluR2 AMPA receptor: structure and dynamics of the complex of two willardiine antagonists with the glutamate binding domain.Biochemistry · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glutamate receptors mediate neuronal intercommunication in the central nervous system by coupling extracellular neurotransmitter-receptor interactions to ion channel conductivity. To gain insight into structural and dynamical factors that underlie this coupling, solution NMR experiments were performed on the bilobed ligand-binding core of glutamate receptor 2 in complexes with a set of willardiine partial agonists. These agonists are valuable for studying structure-function relationships because their 5-position substituent size is correlated with ligand efficacy and extent of receptor desensitization, whereas the substituent electronegativity is correlated with ligand potency. NMR results show that the protein backbone amide chemical shift deviations correlate mainly with efficacy and extent of desensitization. Pronounced deviations occur at specific residues in the ligand-binding site and in the two helical segments that join the lobes by a disulfide bond. Experiments detecting conformational exchange show that micro- to millisecond timescale motions also occur near the disulfide bond and vary largely with efficacy and extent of desensitization. These results thus identify regions displaying structural and dynamical dissimilarity arising from differences in ligand-protein interactions and lobe closure that may play a critical role in receptor response. Furthermore, measures of line broadening and conformational exchange for a portion of the ligand-binding site correlate with ligand EC(50) data. These results do not have any correlate in the currently available crystal structures and thus provide a novel view of ligand-binding events that may be associated with agonist potency differences.
Indexed as
Identifiers
What OpenQuestion holds
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.