EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 3027, Year 2024
掲載日	2024年4月18日
著者	Atsushi Yamagata / Kaori Ito / Takehiro Suzuki / Naoshi Dohmae / Tohru Terada / Mikako Shirouzu /
PubMed 要旨	More than one percent of people have epilepsy worldwide. Levetiracetam (LEV) is a successful new-generation antiepileptic drug (AED), and its derivative, brivaracetam (BRV), shows improved efficacy. ...More than one percent of people have epilepsy worldwide. Levetiracetam (LEV) is a successful new-generation antiepileptic drug (AED), and its derivative, brivaracetam (BRV), shows improved efficacy. Synaptic vesicle glycoprotein 2a (SV2A), a putative membrane transporter in the synaptic vesicles (SVs), has been identified as a target of LEV and BRV. SV2A also serves as a receptor for botulinum neurotoxin (BoNT), which is the most toxic protein and has paradoxically emerged as a potent reagent for therapeutic and cosmetic applications. Nevertheless, no structural analysis on AEDs and BoNT recognition by full-length SV2A has been available. Here we describe the cryo-electron microscopy structures of the full-length SV2A in complex with the BoNT receptor-binding domain, BoNT/A2 H and either LEV or BRV. The large fourth luminal domain of SV2A binds to BoNT/A2 H through protein-protein and protein-glycan interactions. LEV and BRV occupy the putative substrate-binding site in an outward-open conformation. A propyl group in BRV creates additional contacts with SV2A, explaining its higher binding affinity than that of LEV, which was further supported by label-free spectral shift assay. Numerous LEV derivatives have been developed as AEDs and positron emission tomography (PET) tracers for neuroimaging. Our work provides a structural framework for AEDs and BoNT recognition of SV2A and a blueprint for the rational design of additional AEDs and PET tracers.
リンク	Nat Commun / PubMed:38637505 / PubMed Central
手法	EM (単粒子)
解像度	2.82 - 3.38 Å
構造データ	36392 8jlc EMDB-36392, PDB-8jlc: Cryo-EM structure of SV2A in complex with BoNT/A2 Hc and levetiracetam 手法: EM (単粒子) / 解像度: 2.88 Å 36394 8jle EMDB-36394, PDB-8jle: Cryo-EM structure of SV2A LD4 in complex with BoNT/A2 Hc in the SV2A-levetiracetam-BoNT/A2 Hc complex 手法: EM (単粒子) / 解像度: 2.82 Å 36395 8jlf EMDB-36395, PDB-8jlf: Cryo-EM structure of SV2A in complex with BoNT/A2 Hc 手法: EM (単粒子) / 解像度: 3.01 Å 36396 8jlg EMDB-36396, PDB-8jlg: Cryo-EM structure of SV2A in complex with BoNT/A2 Hc 手法: EM (単粒子) / 解像度: 2.87 Å 36397 8jlh EMDB-36397, PDB-8jlh: Cryo-EM structure of SV2A dimer in complex with BoNT/A2 Hc and levetiracetam 手法: EM (単粒子) / 解像度: 2.9 Å 36398 8jli EMDB-36398, PDB-8jli: Cryo-EM structure of SV2A dimer in complex levetiracetam 手法: EM (単粒子) / 解像度: 3.38 Å 36616 8js8 EMDB-36616, PDB-8js8: Cryo-EM structure of SV2A in complex with BoNT/A2 Hc and levetiracetam 手法: EM (単粒子) / 解像度: 2.88 Å 36617 8js9 EMDB-36617, PDB-8js9: Cryo-EM structure of SV2A in complex with BoNT/A2 Hc 手法: EM (単粒子) / 解像度: 3.01 Å EMDB-36933: Cryo-EM map of SV2A in complex with brivaracetam and BoNT/A2 Hc 手法: EM (単粒子) / 解像度: 3.11 Å EMDB-36934: Local map of SV2A LD4-BoNT/A2 Hc from SV2A-BoNT/A2 Hc-brivaracetam complex 手法: EM (単粒子) / 解像度: 3.07 Å 36935 8k77 EMDB-36935, PDB-8k77: Cryo-EM structure of SV2A in complex with BoNT/A2 Hc and brivaracetam 手法: EM (単粒子) / 解像度: 3.11 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン化合物画像なし ChemComp-UKX: Unknown entry 化合物画像なし ChemComp-VLX: Unknown entry
由来	homo sapiens (ヒト) clostridium botulinum (ボツリヌス菌)
キーワード	TRANSPORT PROTEIN / Synaptic vesicle / epilepsy / MEMBRANE PROTEIN / botulinum neurotoxin / Synapse / antiepileptic drug