Extended glutamate activates metabotropic receptor types 1, 2 and 4: selective features at mGluR4 binding site.
To get an insight into the bioactive conformation of glutamic acid and its topological environment at the mGluR4 binding site, a pharmacophore model was constructed using molecular modeling. Agonists of known activities were used to run the Apex-3D program or to validate the resulting model. An extended glutamate conformer, two selective hydrophilic sites and bulk tolerance regions are disclosed. Selective features of mGluR1, mGluR2 and mGluR4 are discussed.
Bessis
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Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR8601-CNRS, Université René Descartes-Paris V, France.
Jullian
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N
Coudert
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Pin
J P
JP
Acher
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F
D000818:Animals; D001665:Binding Sites; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship
D018690:Excitatory Amino Acid Agonists; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; C108823:metabotropic glutamate receptor 4