Conserved asparagine residue located in binding pocket controls cation selectivity and substrate interactions in neuronal glutamate transporter.

ABSTRACT: Transporters of the major excitatory neurotransmitter glutamate play a crucial role in glutamatergic neurotransmission by removing their substrate from the synaptic cleft. The transport mechanism involves co-transport of glutamic acid with three Na(+) ions followed by countertransport of one K(+) ion. Structural work on the archeal homologue Glt(Ph) indicates a role of a conserved asparagine in substrate binding. According to a recent proposal, this residue may also participate in a novel Na(+) binding site. In this study, we characterize mutants of this residue from the neuronal transporter EAAC1, Asn-451. None of the mutants, except for N451S, were able to exhibit transport. However, the K(m) of this mutant for l-aspartate was increased ∼30-fold. Remarkably, the increase for d-aspartate

SUBMITTER: Teichman S 

PROVIDER: S-EPMC3366809 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature