9LK8
Cryo-EM structure of GAT3
Summary for 9LK8
| Entry DOI | 10.2210/pdb9lk8/pdb |
| EMDB information | 63171 |
| Descriptor | Sodium- and chloride-dependent GABA transporter 3, GAMMA-AMINO-BUTANOIC ACID, CHLORIDE ION (3 entities in total) |
| Functional Keywords | protein structure, structual protein, structural protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 70799.01 |
| Authors | |
| Primary citation | Xu, H.,Zhang, Y.,Bai, Q.,He, L.,Chen, Q.,Qiu, Y.,Li, R.,Yu, J.,Zhao, J.,Zhao, Y. Substrate and inhibitor binding of human GABA transporter 3. Structure, 33:2049-2057.e5, 2025 Cited by PubMed Abstract: GABA (g-aminobutyric acid) transporter 3 (GAT3) is primarily found in glial cells and is essential for regulating GABA homeostasis in the central nervous system by mediating GABA uptake. Consequently, GAT3 has emerged as a significant therapeutic target for the treatment of epilepsy. In this study, we present the cryoelectron microscopy (cryo-EM) structures of GAT3 bound to its substrate GABA, the selective inhibitor SNAP-5114, and in the substrate-free state. GAT3 binds to GABA in an inward-facing conformation, while SNAP-5114 occupies the GABA-binding pocket and is stabilized by extensive interactions with surrounding residues. Functional studies reveal that E66 plays a pivotal role in determining the substrate-binding mode and specificity of SNAP-5114 binding. Taken together, our study clarifies the GABA binding mechanism of GAT3 and reveals the molecular basis for the specific inhibition of SNAP-5114, offering valuable insights for developing GAT3 subtypes selective inhibitors, which hold potential as a treatment for epilepsy. PubMed: 40914153DOI: 10.1016/j.str.2025.08.012 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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