Insights into transport mechanism from LeuT engineered to transport tryptophan.

ABSTRACT: LeuT is a bacterial homologue of the neurotransmitter:sodium symporter (NSS) family and, being the only NSS member to have been structurally characterized by X-ray crystallography, is a model protein for studying transporter structure and mechanism. Transport activity in LeuT was hypothesized to require structural transitions between open-to-out and occluded conformations dependent upon protein:ligand binding complementarity. Here, using crystallographic and functional analysis, we show that binding site modification produces changes in both structure and activity that are consistent with complementarity-dependent structural transitions to the occluded state. The mutation I359Q converts the activity of tryptophan from inhibitor to transportable substrate. This mutation changes the local en

SUBMITTER: Piscitelli CL 

PROVIDER: S-EPMC3252571 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature