9VWS
Cryo-EM structure of human serotonin transporter in complex with tesofensine
This is a non-PDB format compatible entry.
Summary for 9VWS
| Entry DOI | 10.2210/pdb9vws/pdb |
| EMDB information | 65401 |
| Descriptor | Sodium-dependent serotonin transporter, CHLORIDE ION, SODIUM ION, ... (5 entities in total) |
| Functional Keywords | cryo-em structure of human serotonin transporter in complex with tesofensine, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 71267.74 |
| Authors | |
| Primary citation | Li, Y.,Meng, Y.,Li, N.,Zhao, J.,Li, R.,Bai, Q.,Wang, G.,Zhao, Y. Structural basis for pharmacotherapeutic action of triple reuptake inhibitors. Nat Commun, 17:61-61, 2025 Cited by PubMed Abstract: Most first-line pharmacotherapeutic strategies for depression aim to boost serotonin and norepinephrine levels. However, 35% of patients with depression do not respond adequately to these treatments or experience adverse side effects. The serotonin-norepinephrine-dopamine reuptake inhibitors, also known as triple reuptake inhibitors (TRIs), are emerging as promising antidepressants with greater potency and fewer side effects. Here, we determine an ensemble of structures of DAT in complex with five distinct TRIs. Tesofensine and dasotraline stabilize DAT in an outward-facing conformation, while centanafadine, ansofaxine, and nefazodone capture the inward-facing conformation. These structures reveal binding poses and interactions involved in the association of inhibitors. Notably, ansofaxine binds at a location which is much closer to the intracellular membrane surface. Through extensive structural analysis, we establish a comprehensive blueprint for the association of these TRIs, which is crucial for future drug development aimed at achieving potent antidepressant with fewer side effect. PubMed: 41392177DOI: 10.1038/s41467-025-66670-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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