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1.
Braz. j. med. biol. res ; 40(11): 1419-1427, Nov. 2007. ilus, tab
Article in English | LILACS | ID: lil-464312

ABSTRACT

Ionotropic glutamate receptors are major excitatory receptors in the central nervous system and also have a far reaching influence in other areas of the body. Their modular nature has allowed for the isolation of the ligand-binding domain and for subsequent structural studies using a variety of spectroscopic techniques. This review will discuss the role of specific ligand:protein interactions in mediating activation in the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype of glutamate receptors as established by various spectroscopic investigations of the GluR2 and GluR4 subunits of this receptor. Specifically, this review will provide an introduction to the insight gained from X-ray crystallography and nuclear magnetic resonance investigations and then go on to focus on studies utilizing vibrational spectroscopy and fluorescence resonance energy transfer to study the behavior of the isolated ligand-binding domain in solution and discuss the importance of specific ligand:protein interactions in the mechanism of receptor activation.


Subject(s)
Humans , Receptors, Glutamate/chemistry , Energy Transfer , Excitatory Amino Acid Antagonists/chemistry , Excitatory Amino Acid Antagonists/metabolism , Ligands , Magnetic Resonance Spectroscopy , Protein Binding , Protein Conformation , Receptors, Glutamate/metabolism , Spectroscopy, Fourier Transform Infrared , Structure-Activity Relationship , /chemistry , /metabolism
2.
Journal of Veterinary Science ; : 185-191, 2002.
Article in English | WPRIM | ID: wpr-22474

ABSTRACT

Using site-directed mutagenesis technique, I have replaced serine 285 and serine 292 with the alanine, and assessed the binding of agonist and signaling such as the inhibition of adenylyl cyclase activity.I have found that serine 292 has an important role in the signal transduction of cannabinoid agonists, HU-210 and CP55940, but not in that of aminoalkylindoles derivatives WIN55,212-2. All mutants express well in protein level determined by western blot using monoclonal antibody HA 11 as compared with the wild type receptor.Interestingly, binding affinity of S285A and S292A mutants with classical cannabinoid agonist HU-243 was somewhat decreased. In signaling assay, the inhibition of adenylyl cyclase by HU-210, CP55940 and WIN55, 212-2 is the same order in both wild type receptor and S285A mutant receptor. However, S292A have been shown that the inhibition curves of adenylyl cyclase activity moved to the right by HU-210 and CP55940, but those of adenylyl cyclase activity did not by aminoalkylindole WIN55,212-2, which is indicating that this residue is closely related to the binding site with HU-210 and CP55940. In addition, serine 292 might take more important role in CB2 receptor and G-protein signaling than serine 285.


Subject(s)
Animals , Adenylyl Cyclases/metabolism , Binding, Competitive , Blotting, Western , COS Cells , Cannabinoids/metabolism , Chlorocebus aethiops , Cyclohexanols/metabolism , Excitatory Amino Acid Antagonists/metabolism , Mutagenesis, Site-Directed , Protein Conformation , Protein Structure, Tertiary , Receptors, Cannabinoid , Receptors, Drug/genetics , Serine/metabolism , Signal Transduction/physiology , Dronabinol , Transfection
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