Visualizing Transporter Structure Creates Platform for Antidepressant Drug Design

Researchers at Oregon Health and Sciences University’s Vollum Institute have revealed the molecular structure of the serotonin transporter (SERT), providing new insight into the mechanism of antidepressant action of two widely prescribed selective serotonin reuptake inhibitors (SSRIs) commonly used to treat depression. In their Nature paper, authors Jonathan Coleman, Evan Green, and Eric Gouaux describe their use of X-ray crystallography to capture images of human SERT structures. They collected data at Beamline 5.0.2 in the Berkeley Center for Structural Biology and used the Phenix software suite to build models and refine the structures. The resulting structures show antidepressants citalopram and paroxetine lock SERT in an outward-open conformation, directly blocking serotonin binding. Visualizing this structure provides a blueprint for future drug design to treat anxiety and depression. This work was highlighted by Nature News and OHSU News.