View source for 8jlc


==Cryo-EM structure of SV2A in complex with BoNT/A2 Hc and levetiracetam==
<StructureSection load='8jlc' size='340' side='right'caption='[[8jlc]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jlc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JLC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UKX:(2~{S})-2-(2-oxidanylidenepyrrolidin-1-yl)butanamide'>UKX</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8jlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jlc OCA], [https://pdbe.org/8jlc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jlc RCSB], [https://www.ebi.ac.uk/pdbsum/8jlc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jlc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SV2A_HUMAN SV2A_HUMAN] Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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(C,) and either LEV or BRV. The large fourth luminal domain of SV2A binds to BoNT/A2 H(C) 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.

Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A.,Yamagata A, Ito K, Suzuki T, Dohmae N, Terada T, Shirouzu M Nat Commun. 2024 Apr 18;15(1):3027. doi: 10.1038/s41467-024-47322-4. PMID:38637505<ref>PMID:38637505</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8jlc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Clostridium botulinum]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Yamagata A]]