Highlights •Large-library docking finds conformationally and target-selective SERT inhibitors •Cryo-EM supports the computationally predicted structure •The inhibitors are anti-depressant-like and alleviate opioid withdrawal in mice •Targeting of transporters for structure-based ligand discovery 5-hydroxytryptamine transporter (SERT) is a common target for antidepressants as it can “transport” serotonin from synapses. Transporting protein transporters is a process of “swallowing and vomiting”, completed by alternating protein conformations opening outward and inward. Research…
SERT
Antidepressant Target-Serotonin Transporter Reveals Its Shape
Prozac and its kin — drugs called selective serotonin reuptake inhibitors (SSRIs) — were first discovered in 1972. They address one hallmark of depression: low levels of the molecule serotonin, which neurons use to signal one another. By preventing a protein called serotonin transporter (SERT) form absorbing the serotonin back into neurons that release it, the drugs boost serotonin levels in the junctions between cells. It is exciting that the…