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• W2024187762 endingPage "18374" @default.
• W2024187762 startingPage "18369" @default.
• W2024187762 abstract "Significance Morphine and related compounds are the gold standard for the management of pain. Such drugs bind to the orthosteric site on the mu-opioid receptor (MOPr), a G protein-coupled receptor (GPCR). We have proposed that targeting an allosteric site on MOPr could result in improved pain management and have reported positive allosteric modulators (PAMs) of MOPr. High-resolution X-ray structures have identified a Na + binding site on multiple GPCRs and have shown how bound Na + stabilizes inactive receptor states. Here we demonstrate that PAM activity at MOPr allosterically disrupts Na + binding, thereby forming an active-state receptor. The Na + binding site is highly conserved across class A GPCRs so this may represent a fundamental mechanism of allosteric modulation." @default.
• W2024187762 created "2016-06-24" @default.
• W2024187762 creator A5022375777 @default.
• W2024187762 creator A5058049840 @default.
• W2024187762 date "2014-12-08" @default.
• W2024187762 modified "2023-10-16" @default.
• W2024187762 title "Disruption of the Na ⁺ ion binding site as a mechanism for positive allosteric modulation of the mu-opioid receptor" @default.
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• W2024187762 doi "https://doi.org/10.1073/pnas.1415013111" @default.
• W2024187762 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4280615" @default.
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