Crystal Structure and Pharmacological Characterization of a Novel NMDA Receptor Antagonist at the GluN1 Glycine Binding Site
نویسندگان
چکیده
From Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Schrödinger, Inc. 120 West 45 St., New York, NY 10036, USA. Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA. ! Running title: Molecular Mechanism of a Novel GluN1 Glycine-Site Antagonist ! To whom correspondence should be addressed: Hans Bräuner-Osborne, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Fruebjergvej 3, DK2100 Copenhagen, Denmark, Phone: (+45) 3917 9659, E-mail: [email protected] !
منابع مشابه
Crystal structure and pharmacological characterization of a novel N-methyl-D-aspartate (NMDA) receptor antagonist at the GluN1 glycine binding site.
NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission in the brain. They are tetrameric complexes composed of glycine-binding GluN1 and GluN3 subunits together with glutamate-binding GluN2 subunits. Subunit-selective antagonists that discriminate between the glycine sites of GluN1 and GluN3 subunits would be valuable pharmacological tools for studies on the func...
متن کاملStructure-based discovery of antagonists for GluN3-containing N-methyl-D-aspartate receptors.
NMDA receptors are ligand-gated ion channels that assemble into tetrameric receptor complexes composed of glycine-binding GluN1 and GluN3 subunits (GluN3A-B) and glutamate-binding GluN2 subunits (GluN2A-D). NMDA receptors can assemble as GluN1/N2 receptors and as GluN3-containing NMDA receptors, which are either glutamate/glycine-activated triheteromeric GluN1/N2/N3 receptors or glycine-activat...
متن کاملSubunit-selective allosteric inhibition of glycine binding to NMDA receptors.
NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission in the brain and are involved in numerous neuropathological conditions. NMDA receptors are activated upon simultaneous binding of coagonists glycine and glutamate to the GluN1 and GluN2 subunits, respectively. Subunit-selective modulation of NMDA receptor function by ligand binding to modulatory sites distinc...
متن کاملDirect pharmacological monitoring of the developmental switch in NMDA receptor subunit composition using TCN 213, a GluN2A-selective, glycine-dependent antagonist
BACKGROUND AND PURPOSE Developmental switches in NMDA receptor subunit expression have been inferred from studies of GluN2 expression levels, changes in kinetics of glutamatergic synaptic currents and sensitivity of NMDA receptor-mediated currents to selective GluN2B antagonists. Here we use TCN 213, a novel GluN2A-selective antagonist to identify the presence of this subunit in functional NMDA...
متن کاملStructural Mechanism of N-Methyl-D-Aspartate Receptor Type 1 Partial Agonism
N-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that contribute to the signal transmission in the central nervous system. NMDA receptors are heterotetramers that usually consist of two GluN1 and GluN2 monomers. The extracellular ligand-binding domain (LBD) of a monomer is comprised of discontinuous segments that form the functional domains D1 and D2. W...
متن کامل