Probing norepinephrine transporter (NET) structure-function (2012-2014)
Abstract
The transporter for noradrenaline (NET) is an important regulatory protein found in the cell membrane of noradrenergic nerves. We have recently identified a second norepinephrine translocation site in the mouth of NET that appears to be gated by a tryptophan. Our aims are to (i) use site-directed mutagenenesis to define the role of W80 and adjacent residues in substrate transport and ligand binding, and (ii) develop predictive molecular models of hNET that describe the step-wise transport of substrate and where small molecule and conotoxin inhibitors bind. Achieving these aims will facilitate the design of more selective NET inhibitors for the treatment of diseases including pain and depression.
