title: Binding modes of noncompetitive AMPA antagonists: a computational approach.
abstract: The activity of functional AMPA receptors (AMPARs) is modulated by noncompetitive antagonists. So far, no information about the molecular mechanism of action and the localization of the binding pocket(s) is available. We speculated that the leucine/isoleucine/valine binding protein (LIVBP)-like domain of AMPAR, localized at the extracellular N-terminus of the receptor, might be involved in the binding of noncompetitive antagonists and we tested this hypothesis through a computational approach involving the comparison with NMDA and metabotropic glutamate receptors and the generation of a 3D homology model of the LIVBP-like domain of AMPAR. The results suggest that the interdomain cleft of the LIVBP-like domain of AMPAR may contain the noncompetitive antagonist binding pocket.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata 98168, Messina, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Costantino
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Barreca
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
authors.forename: Roberto
authors.initials: R
authors.lastname: Pellicciari
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D019295:Computational Biology / Q000379:methods*; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA