Microseconds simulations reveal a new sodium-binding site and the mechanism of sodium-coupled substrate uptake by LeuT.

ABSTRACT: The bacterial sodium-coupled leucine/alanine transporter LeuT is broadly used as a model system for studying the transport mechanism of neurotransmitters because of its structural and functional homology to mammalian transporters such as serotonin, dopamine, or norepinephrine transporters, and because of the resolution of its structure in different states. Although the binding sites (S1 for substrate, and Na1 and Na2 for two co-transported sodium ions) have been resolved, we still lack a mechanistic understanding of coupled Na(+)- and substrate-binding events. We present here results from extensive (>20 μs) unbiased molecular dynamics simulations generated using the latest computing technology. Simulations show that sodium binds initially the Na1 site, but not Na2, and, consistently, sodiu

SUBMITTER: Zomot E 

PROVIDER: S-EPMC4281755 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature