Thursday, November 14, 2013
Publication and contact
Engineered bacterial LeuT
to detail antidepressant binding mechanisms
An engineered bacterial
homolog of eukaryotic biogenic amine transporters could be useful for
informing how marketed antidepressants interact with their targets. Biogenic
amine transporters are targeted by classes of drugs including selective serotonin
reuptake inhibitors, serotonin-noradrenaline reuptake inhibitors and
tricyclic antidepressants. Bacterial LeuT was engineered to have human
biogenic amine transporter-like pharmacology and then crystallized in complex
with drugs from four classes of antidepressants. Crystallographic analysis
showed that drugs from all four antidepressant classes have similar modes of
binding to the engineered LeuT and lock the protein in an outward-facing,
open conformation. Next steps could include generating additional crystal
structures of LeuT in complex with additional drug classes and using this
information to inform compound design.
Published online Nov. 14, 2013
Patent and licensing status
Wang, H. et al. Nature;
published online Oct. 13, 2013;
Contact: Eric Gouaux, Oregon Health & Science
University, Portland, Ore.
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