Matches in SemOpenAlex for { <https://semopenalex.org/work/W4230407570> ?p ?o ?g. }
- W4230407570 abstract "Abstract Context-dependent inhibition of N -methyl-D-aspartate (NMDA) receptors has important therapeutic implications for the treatment of neurological diseases that are associated with altered neuronal firing and signaling. This is especially true in stroke, where the proton concentration in the afflicted area can increase by an order of magnitude. A class of allosteric inhibitors, the 93-series, shows greater potency against GluN1-GluN2B NMDA receptors in such low pH environments, allowing targeted therapy only within the ischemic region. Here we map the 93-series compound binding site in the GluN1-GluN2B NMDA receptor amino terminal domain and show that the interaction of the N-alkyl group with a hydrophobic cage of the binding site is critical for pH-dependent inhibition. Mutation of residues in the hydrophobic cage alters pH-dependent potency, and remarkably, can convert inhibitors into potentiators. Our study provides a foundation for the development of highly specific neuroprotective compounds for the treatment of neurological diseases." @default.
- W4230407570 created "2022-05-11" @default.
- W4230407570 creator A5007211751 @default.
- W4230407570 creator A5017011355 @default.
- W4230407570 creator A5032077625 @default.
- W4230407570 creator A5032949226 @default.
- W4230407570 creator A5039738992 @default.
- W4230407570 creator A5041161550 @default.
- W4230407570 creator A5051202816 @default.
- W4230407570 creator A5086553722 @default.
- W4230407570 creator A5091825209 @default.
- W4230407570 date "2019-01-18" @default.
- W4230407570 modified "2023-10-01" @default.
- W4230407570 title "Structural elements of a pH-sensitive inhibitor binding site in NMDA receptors" @default.
- W4230407570 cites W157021211 @default.
- W4230407570 cites W1774281578 @default.
- W4230407570 cites W1903831724 @default.
- W4230407570 cites W1980311878 @default.
- W4230407570 cites W1994732950 @default.
- W4230407570 cites W2005416458 @default.
- W4230407570 cites W2008351358 @default.
- W4230407570 cites W2011243320 @default.
- W4230407570 cites W2013172353 @default.
- W4230407570 cites W2024380057 @default.
- W4230407570 cites W2036968549 @default.
- W4230407570 cites W2037852973 @default.
- W4230407570 cites W2038301210 @default.
- W4230407570 cites W2042742187 @default.
- W4230407570 cites W2047397795 @default.
- W4230407570 cites W2078130861 @default.
- W4230407570 cites W2089094370 @default.
- W4230407570 cites W2093954744 @default.
- W4230407570 cites W2095447700 @default.
- W4230407570 cites W2097095684 @default.
- W4230407570 cites W2112445212 @default.
- W4230407570 cites W2113000521 @default.
- W4230407570 cites W2134544862 @default.
- W4230407570 cites W2139976683 @default.
- W4230407570 cites W2162454135 @default.
- W4230407570 cites W2164370979 @default.
- W4230407570 cites W2174668858 @default.
- W4230407570 cites W2274889205 @default.
- W4230407570 cites W2294208894 @default.
- W4230407570 cites W2343219805 @default.
- W4230407570 cites W2537627674 @default.
- W4230407570 cites W2558403885 @default.
- W4230407570 cites W2581539125 @default.
- W4230407570 cites W2590999072 @default.
- W4230407570 cites W2611061689 @default.
- W4230407570 cites W2796905767 @default.
- W4230407570 cites W2891053092 @default.
- W4230407570 cites W2900144052 @default.
- W4230407570 doi "https://doi.org/10.1038/s41467-019-08291-1" @default.
- W4230407570 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30659174" @default.
- W4230407570 hasPublicationYear "2019" @default.
- W4230407570 type Work @default.
- W4230407570 citedByCount "30" @default.
- W4230407570 countsByYear W42304075702019 @default.
- W4230407570 countsByYear W42304075702020 @default.
- W4230407570 countsByYear W42304075702021 @default.
- W4230407570 countsByYear W42304075702022 @default.
- W4230407570 countsByYear W42304075702023 @default.
- W4230407570 crossrefType "journal-article" @default.
- W4230407570 hasAuthorship W4230407570A5007211751 @default.
- W4230407570 hasAuthorship W4230407570A5017011355 @default.
- W4230407570 hasAuthorship W4230407570A5032077625 @default.
- W4230407570 hasAuthorship W4230407570A5032949226 @default.
- W4230407570 hasAuthorship W4230407570A5039738992 @default.
- W4230407570 hasAuthorship W4230407570A5041161550 @default.
- W4230407570 hasAuthorship W4230407570A5051202816 @default.
- W4230407570 hasAuthorship W4230407570A5086553722 @default.
- W4230407570 hasAuthorship W4230407570A5091825209 @default.
- W4230407570 hasBestOaLocation W42304075701 @default.
- W4230407570 hasConcept C107824862 @default.
- W4230407570 hasConcept C12554922 @default.
- W4230407570 hasConcept C151730666 @default.
- W4230407570 hasConcept C164718446 @default.
- W4230407570 hasConcept C166342909 @default.
- W4230407570 hasConcept C169760540 @default.
- W4230407570 hasConcept C170493617 @default.
- W4230407570 hasConcept C17077164 @default.
- W4230407570 hasConcept C185592680 @default.
- W4230407570 hasConcept C202751555 @default.
- W4230407570 hasConcept C25498285 @default.
- W4230407570 hasConcept C2778938600 @default.
- W4230407570 hasConcept C2779343474 @default.
- W4230407570 hasConcept C55493867 @default.
- W4230407570 hasConcept C57992300 @default.
- W4230407570 hasConcept C67018056 @default.
- W4230407570 hasConcept C86803240 @default.
- W4230407570 hasConcept C98274493 @default.
- W4230407570 hasConceptScore W4230407570C107824862 @default.
- W4230407570 hasConceptScore W4230407570C12554922 @default.
- W4230407570 hasConceptScore W4230407570C151730666 @default.
- W4230407570 hasConceptScore W4230407570C164718446 @default.
- W4230407570 hasConceptScore W4230407570C166342909 @default.
- W4230407570 hasConceptScore W4230407570C169760540 @default.
- W4230407570 hasConceptScore W4230407570C170493617 @default.
- W4230407570 hasConceptScore W4230407570C17077164 @default.
- W4230407570 hasConceptScore W4230407570C185592680 @default.