8jlh: Difference between revisions

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-'''Unreleased structure'''
-The entry 8jlh is ON HOLD
+==Cryo-EM structure of SV2A dimer in complex with BoNT/A2 Hc and levetiracetam==
+<StructureSection load='8jlh' size='340' side='right'caption='[[8jlh]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8jlh]] is a 4 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=8JLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JLH 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]] 2.9&#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=8jlh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jlh OCA], [https://pdbe.org/8jlh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jlh RCSB], [https://www.ebi.ac.uk/pdbsum/8jlh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jlh 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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8jlh" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Clostridium botulinum]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Yamagata A]]