8UO8

Structure of synaptic vesicle protein 2B with padsevonil

これはPDB形式変換不可エントリーです。

8UO8 の概要

• エントリーDOI: 10.2210/pdb8uo8/pdb
• EMDBエントリー: 42430
• 分子名称: 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)
• 機能のキーワード: synaptic vesicle, slc22, inhibitor, antiepileptic, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 81124.77

構造登録者

Martin, M.F.,Mittal, A.,Levin, E.,Adams, C.,Yang, M.,Ledecq, M.,Horanyi, P.S.,Coleman, J.A. (登録日: 2023-10-19, 公開日: 2024-05-22, 最終更新日: 2024-12-25)

主引用文献

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., 31:1964-1974, 2024

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: 38898101
DOI: 10.1038/s41594-024-01335-1

実験手法

ELECTRON MICROSCOPY (3.2 Å)