8UO8
Structure of synaptic vesicle protein 2B with padsevonil
This is a non-PDB format compatible entry.
Summary for 8UO8
| Entry DOI | 10.2210/pdb8uo8/pdb |
| EMDB information | 42430 |
| Descriptor | Synaptic vesicle glycoprotein 2B, 2-acetamido-2-deoxy-beta-D-glucopyranose, (4R)-4-(2-chloro-2,2-difluoroethyl)-1-{[(4R)-2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one, ... (8 entities in total) |
| Functional Keywords | synaptic vesicle, slc22, inhibitor, antiepileptic, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 81124.77 |
| Authors | Martin, M.F.,Mittal, A.,Levin, E.,Adams, C.,Yang, M.,Ledecq, M.,Horanyi, P.S.,Coleman, J.A. (deposition date: 2023-10-19, release date: 2024-05-22, Last modification date: 2024-10-23) |
| Primary citation | Mittal, A.,Martin, M.F.,Levin, E.J.,Adams, C.,Yang, M.,Provins, L.,Hall, A.,Procter, M.,Ledecq, M.,Hillisch, A.,Wolff, C.,Gillard, M.,Horanyi, P.S.,Coleman, J.A. Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants. Nat.Struct.Mol.Biol., 2024 Cited by PubMed Abstract: Epilepsy is a common neurological disorder characterized by abnormal activity of neuronal networks, leading to seizures. The racetam class of anti-seizure medications bind specifically to a membrane protein found in the synaptic vesicles of neurons called synaptic vesicle protein 2 (SV2) A (SV2A). SV2A belongs to an orphan subfamily of the solute carrier 22 organic ion transporter family that also includes SV2B and SV2C. The molecular basis for how anti-seizure medications act on SV2s remains unknown. Here we report cryo-electron microscopy structures of SV2A and SV2B captured in a luminal-occluded conformation complexed with anticonvulsant ligands. The conformation bound by anticonvulsants resembles an inhibited transporter with closed luminal and intracellular gates. Anticonvulsants bind to a highly conserved central site in SV2s. These structures provide blueprints for future drug design and will facilitate future investigations into the biological function of SV2s. PubMed: 38898101DOI: 10.1038/s41594-024-01335-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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