| http://purl.uniprot.org/citations/29576321 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29576321 | http://www.w3.org/2000/01/rdf-schema#comment | "Small conductance potassium (SK) ion channels define neuronal firing rates by conducting the after-hyperpolarization current. They are key targets in developing therapies where neuronal firing rates are dysfunctional, such as in epilepsy, Parkinson's, and amyotrophic lateral sclerosis (ALS). Here, we characterize a binding pocket situated at the intracellular interface of SK2 and calmodulin, which we show to be shared by multiple small-molecule chemotypes. Crystallization of this complex revealed that riluzole (approved for ALS) and an analog of the anti-ataxic agent (4-chloro-phenyl)-[2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidin-4-yl]-amine (CyPPA) bind to and allosterically modulate via this site. Solution-state nuclear magnetic resonance demonstrates that riluzole, NS309, and CyPPA analogs bind at this bipartite pocket. We demonstrate, by patch-clamp electrophysiology, that both classes of ligand interact with overlapping but distinct residues within this pocket. These data define a clinically important site, laying the foundations for further studies of the mechanism of action of riluzole and related molecules."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.str.2018.02.017"xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Liu S."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Bell S."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Taylor T."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Horst R."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Withka J.M."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Pandit J."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Knafels J."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Torella R."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Hobbs J."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Young G.T."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Cho L.T."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Stevens E.B."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Pryde D.C."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Konopacka A."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Alexandrou A.J."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/author | "Loucif A."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/name | "Structure"xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/pages | "533-544.e3"xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/title | "An Intracellular Allosteric Modulator Binding Pocket in SK2 Ion Channels Is Shared by Multiple Chemotypes."xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://purl.uniprot.org/core/volume | "26"xsd:string |
| http://purl.uniprot.org/citations/29576321 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29576321 |