Structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters

Abstract

The Drosophila dopamine transporter (dDAT) is a catecholamine neurotransmitter transporter that resembles the human norepinephrine transporter (hNET). Here the authors report X-ray structures of the dDAT in substrate-free form, norepinephrine-bound form and dDAT bound to commonly prescribed chronic pain inhibitors duloxetine, milnacipran and tramadol and shed light on the structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters.