Structure-based discovery of prescription drugs that interact with the norepinephrine transporter, NET.

ABSTRACT: The norepinephrine transporter (NET) transports norepinephrine from the synapse into presynaptic neurons, where norepinephrine regulates signaling pathways associated with cardiovascular effects and behavioral traits via binding to various receptors (e.g., β2-adrenergic receptor). NET is a known target for a variety of prescription drugs, including antidepressants and psychostimulants, and may mediate off-target effects of other prescription drugs. Here, we identify prescription drugs that bind NET, using virtual ligand screening followed by experimental validation of predicted ligands. We began by constructing a comparative structural model of NET based on its alignment to the atomic structure of a prokaryotic NET homolog, the leucine transporter LeuT. The modeled binding site was validat

SUBMITTER: Schlessinger A 

PROVIDER: S-EPMC3179104 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature