View source for 8uo8


==Structure of synaptic vesicle protein 2B with padsevonil==
<StructureSection load='8uo8' size='340' side='right'caption='[[8uo8]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8uo8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UO8 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=43Y:[(2R)-3-[OXIDANYL-[2-(TRIMETHYL-$L^{4}-AZANYL)ETHOXY]PHOSPHORYL]OXY-2-PROPANOYLOXY-PROPYL]+PROPANOATE'>43Y</scene>, <scene name='pdbligand=9Z9:(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en'>9Z9</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PS1:1,2-DIDECANOYL-SN-GLYCERO-3-[PHOSPHO-L-SERINE]'>PS1</scene>, <scene name='pdbligand=X3U:(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'>X3U</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=8uo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uo8 OCA], [https://pdbe.org/8uo8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uo8 RCSB], [https://www.ebi.ac.uk/pdbsum/8uo8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uo8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SV2B_HUMAN SV2B_HUMAN] Probably plays a role in the control of regulated secretion in neural and endocrine cells.  (Microbial infection) Receptor for the C.botulinum neurotoxin type A2 (BoNT/A, botA); glycosylation is not essential but enhances the interaction (PubMed:29649119). Probably also serves as a receptor for the closely related C.botulinum neurotoxin type A1.<ref>PMID:29649119</ref> <ref>PMID:29649119</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.,Mittal A, Martin MF, Levin EJ, Adams C, Yang M, Provins L, Hall A, Procter M, Ledecq M, Hillisch A, Wolff C, Gillard M, Horanyi PS, Coleman JA Nat Struct Mol Biol. 2024 Jun 19. doi: 10.1038/s41594-024-01335-1. PMID:38898101<ref>PMID:38898101</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8uo8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Adams C]]
[[Category: Coleman JA]]
[[Category: Horanyi PS]]
[[Category: Ledecq M]]
[[Category: Levin E]]
[[Category: Martin MF]]
[[Category: Mittal A]]
[[Category: Yang M]]