| http://purl.uniprot.org/citations/26912815 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26912815 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26912815 | http://www.w3.org/2000/01/rdf-schema#comment | "N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels that play key roles in brain physiology and pathology. Because numerous pathologic conditions involve NMDAR overactivation, subunit-selective antagonists hold strong therapeutic potential, although clinical successes remain limited. Among the most promising NMDAR-targeting drugs are allosteric inhibitors of GluN2B-containing receptors. Since the discovery of ifenprodil, a range of GluN2B-selective compounds with strikingly different structural motifs have been identified. This molecular diversity raises the possibility of distinct binding sites, although supporting data are lacking. Using X-ray crystallography, we show that EVT-101, a GluN2B antagonist structurally unrelated to the classic phenylethanolamine pharmacophore, binds at the same GluN1/GluN2B dimer interface as ifenprodil but adopts a remarkably different binding mode involving a distinct subcavity and receptor interactions. Mutagenesis experiments demonstrate that this novel binding site is physiologically relevant. Moreover, in silico docking unveils that GluN2B-selective antagonists broadly divide into two distinct classes according to binding pose. These data widen the allosteric and pharmacological landscape of NMDARs and offer a renewed structural framework for designing next-generation GluN2B antagonists with therapeutic value for brain disorders."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.115.103036"xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.115.103036"xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Pandit J."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Pandit J."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Knafels J.D."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Knafels J.D."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Green M."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Green M."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Chanda P.K."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Chanda P.K."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Stroebel D."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Stroebel D."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Buhl D.L."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Buhl D.L."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Mony L."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Mony L."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Paoletti P."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Paoletti P."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Sciabola S."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/author | "Sciabola S."xsd:string |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26912815 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |