Free-Energy Simulations Resolve the Low-Affinity Na⁺-High-Affinity Asp Binding Paradox in Glt_Ph.

ABSTRACT: Glutamate transporters clear up excess extracellular glutamate by cotransporting three Na⁺ and one H⁺ with the countertransport of one K⁺. The archaeal homologs are selective to aspartate and only cotransport three Na⁺. The crystal structures of Glt_Ph from archaea have been used in computational studies to understand the transport mechanism. Although some progress has been made with regard to the ligand-binding sites, a consistent picture of transport still eludes us. A major concern is the discrepancy between the computed binding free energies, which predict high-affinity Na⁺-low-affinity aspartate binding, and the experimental results in which the opposite is observed. Here, we show that the binding of the first two Na

SUBMITTER: Setiadi J 

PROVIDER: S-EPMC6712548 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature