Structural basis of vilazodone dual binding mode to the serotonin transporter.

• Tác giả: Nathan Adams, Iris Kalenderoglou, Claus Loland, Amy Newman, Andreas Nygaard, Tillmann Pape, Anton Turaev, Caleb Vogt
• Ngôn ngữ: eng
• Thông tin xuất bản: United States : Research square , 2025
• Bộ sưu tập: NCBI
• ID: 732494

Tóm tắt

The serotonin transporter (SERT) plays a pivotal role in regulating serotonin (5-HT) signaling and is a key target in treating psychiatric disorders. SERT has a binding site (S1) for 5-HT that also serves as a high-affinity binding site for antidepressants. The antidepressant vilazodone has been shown to inhibit SERT by binding to an allosteric site. Here, we present the cryo-EM structure of SERT with vilazodone bound to the S1 site and extending towards the allosteric site. We systematically dissect the vilazodone molecule into fragments and find that the terminal indole ring is the key determinant for its high affinity to SERT. Further, unlike typical Na