Mechanisms of activation, inhibition and specificity: crystal structures of the NMDA receptor NR1 ligand-binding core. Export

@article{citeulike:1577076, abstract = {Excitatory neurotransmission mediated by the N-methyl-D-aspartate subtype of ionotropic glutamate receptors is fundamental to the development and function of the mammalian central nervous system. NMDA receptors require both glycine and glutamate for activation with NR1 and NR2 forming glycine and glutamate sites, respectively. Mechanisms to describe agonist and antagonist binding, and activation and desensitization of NMDA receptors have been hampered by the lack of high-resolution structures. Here, we describe the cocrystal structures of the NR1 S1S2 ligand-binding core with the agonists glycine and D-serine (DS), the partial agonist D-cycloserine (DCS) and the antagonist 5,7-dichlorokynurenic acid (DCKA). The cleft of the S1S2 'clamshell' is open in the presence of the antagonist DCKA and closed in the glycine, DS and DCS complexes. In addition, the NR1 S1S2 structure reveals the fold and interactions of loop 1, a cysteine-rich region implicated in intersubunit allostery.}, address = {Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, NY 10032, USA.}, author = {Furukawa, H. and Gouaux, E.}, citeulike-article-id = {1577076}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/12805203}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=12805203}, day = {16}, issn = {0261-4189}, journal = {EMBO J}, keywords = {docking, ion\_channels, nmda, nr1, sar}, month = {June}, number = {12}, pages = {2873--2885}, posted-at = {2008-07-20 16:10:50}, priority = {5}, title = {Mechanisms of activation, inhibition and specificity: crystal structures of the NMDA receptor NR1 ligand-binding core.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12805203}, volume = {22}, year = {2003} }

TY - JOUR ID - citeulike:1577076 L3 - citeulike-article-id:1577076 N2 - Excitatory neurotransmission mediated by the N-methyl-D-aspartate subtype of ionotropic glutamate receptors is fundamental to the development and function of the mammalian central nervous system. NMDA receptors require both glycine and glutamate for activation with NR1 and NR2 forming glycine and glutamate sites, respectively. Mechanisms to describe agonist and antagonist binding, and activation and desensitization of NMDA receptors have been hampered by the lack of high-resolution structures. Here, we describe the cocrystal structures of the NR1 S1S2 ligand-binding core with the agonists glycine and D-serine (DS), the partial agonist D-cycloserine (DCS) and the antagonist 5,7-dichlorokynurenic acid (DCKA). The cleft of the S1S2 'clamshell' is open in the presence of the antagonist DCKA and closed in the glycine, DS and DCS complexes. In addition, the NR1 S1S2 structure reveals the fold and interactions of loop 1, a cysteine-rich region implicated in intersubunit allostery. IS - 12 JF - EMBO J SN - 0261-4189 AD - Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, NY 10032, USA. EP - 2885 TI - Mechanisms of activation, inhibition and specificity: crystal structures of the NMDA receptor NR1 ligand-binding core. VL - 22 SP - 2873 KW - docking KW - ion_channels KW - nmda KW - nr1 KW - sar AU - Furukawa, H AU - Gouaux, E PY - 2003/06/16/ UR - http://view.ncbi.nlm.nih.gov/pubmed/12805203 ER -