Competition between Li⁺ and Na⁺ in sodium transporters and receptors: Which Na⁺-Binding sites are "therapeutic" Li⁺ targets?

ABSTRACT: Sodium (Na⁺) acts as an indispensable allosteric regulator of the activities of biologically important neurotransmitter transporters and G-protein coupled receptors (GPCRs), which comprise well-known drug targets for psychiatric disorders and addictive behavior. How selective these allosteric Na⁺-binding sites are for the cognate cation over abiogenic Li⁺, a first-line drug to treat bipolar disorder, is unclear. Here, we reveal how properties of the host protein and its binding cavity affect the outcome of the competition between Li⁺ and Na⁺ for allosteric binding sites in sodium transporters and receptors. We show that rigid Na⁺-sites that are crowded with multiple protein ligands are well-protected against Li⁺ a

SUBMITTER: Dudev T 

PROVIDER: S-EPMC5944251 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature