9W8J
Transport and inhibition mechanisms of human glycine transporter 2
This is a non-PDB format compatible entry.
Summary for 9W8J
| Entry DOI | 10.2210/pdb9w8j/pdb |
| EMDB information | 65747 |
| Descriptor | Sodium- and chloride-dependent glycine transporter 2, 4-butoxy-~{N}-[[4-(dimethylamino)oxan-4-yl]methyl]-3,5-dimethoxy-benzamide, SODIUM ION, ... (4 entities in total) |
| Functional Keywords | glyt2, membrane transport protein, opiranserin, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 67510.64 |
| Authors | |
| Primary citation | Ji, W.,Yu, Y.,Liu, Z.,Su, J.,Wang, Q.,Lai, M.,Wu, J.X. Transport and inhibition mechanisms of human glycine transporter 2. Nat Commun, 2026 Cited by PubMed Abstract: Neuronal human glycine transporter 2 (hGlyT2) plays a critical role in maintaining glycinergic neurotransmission via the reuptake of glycine into presynaptic neurons by using the driving force of sodium and chloride ion gradients. hGlyT2 represents an important drug target for analgesic purpose. However, its structure and the molecular mechanisms remain elusive. Here, we report structures of hGlyT2 in three functional states, including the apo state, the substrate glycine-bound state, and the inhibitor-bound states. The apo state of hGlyT2 adopts an inward conformation. The substrate glycine binds at the central pocket of hGlyT2 in its occluded conformation. Both inhibitors, ORG25543 and opiranserin, bind to an allosteric site, which is vertical to the extracellular tunnel, buried under the extracellular loop 4 (EL4) and near to the transmembrane helix 1b (TM1b). These inhibitors act as wedges to prevent the inward movement of TM1b and closure of the extracellular gate. Further structural analysis reveals both global and local conformational changes associated with the ions and glycine binding and release. These structures define the mechanisms governing transport and allosteric inhibition in hGlyT2, providing a blueprint for further development of non-opioid analgesics targeting hGlyT2. PubMed: 41991951DOI: 10.1038/s41467-026-71935-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.73 Å) |
Structure validation
No wwPDB Validation report is currently available for this entry.
