Substrate binds in the S1 site of the F253A mutant of LeuT, a neurotransmitter sodium symporter homologue.

ABSTRACT: LeuT serves as the model protein for understanding the relationships between structure, mechanism and pharmacology in neurotransmitter sodium symporters (NSSs). At the present time, however, there is a vigorous debate over whether there is a single high-affinity substrate site (S1) located at the original, crystallographically determined substrate site or whether there are two high-affinity substrates sites, one at the primary or S1 site and the other at a second site (S2) located at the base of the extracellular vestibule. In an effort to address the controversy over the number of high-affinity substrate sites in LeuT, one group studied the F253A mutant of LeuT and asserted that in this mutant substrate binds exclusively to the S2 site and that 1 mM clomipramine entirely ablates substrate

SUBMITTER: Wang H 

PROVIDER: S-EPMC3432802 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature