Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural pharmacology of SV2A reveals an allosteric modulation mechanism in the major facilitator superfamily.
Journal, issue, pages	Nat Commun, Vol. 16, Issue 1, Page 10748, Year 2025
Publish date	Nov 28, 2025
Authors	Shabareesh Pidathala / Xiao Chen / Yaxin Dai / Long N Nguyen / Christoph Gorgulla / Yiming Niu / Fangyu Liu / Chia-Hsueh Lee /
PubMed Abstract	The synaptic vesicle glycoprotein 2A (SV2A), a member of the major facilitator superfamily (MFS), is a key target for antiseizure medications and a biomarker for synaptic density imaging. Despite its ...The synaptic vesicle glycoprotein 2A (SV2A), a member of the major facilitator superfamily (MFS), is a key target for antiseizure medications and a biomarker for synaptic density imaging. Despite its clinical importance, the mechanisms underlying SV2A ligand binding and modulation remain poorly understood. Here, we report sub-3 Å resolution cryo-electron microscopy (cryo-EM) structures of human SV2A in its apo form and in complex with FDA-approved antiseizure medication levetiracetam; PET imaging tracer UCB-J; experimental antiseizure drug padsevonil; and allosteric modulator UCB1244283. We find that levetiracetam and UCB-J induce vestibule occlusion, a hallmark conformational transition of MFS transporters that had not been observed in previous SV2A structures. UCB1244283 binds to an allosteric site and enhances orthosteric ligand engagement by stabilizing the occluded state and slowing ligand dissociation. Notably, padsevonil occupies both orthosteric and allosteric sites, functionally precluding modulation. These findings uncover an allosteric mechanism of regulation and provide a structural framework for the development of modulators targeting SV2A and related MFS transporters.
External links	Nat Commun / PubMed:41315229 / PubMed Central
Methods	EM (single particle)
Resolution	2.39 - 3.03 Å
Structure data	70562 9okf EMDB-70562, PDB-9okf: Cryo-EM structure of human SV2A in the apo state Method: EM (single particle) / Resolution: 2.8 Å 70563 9okg EMDB-70563, PDB-9okg: Cryo-EM structure of human SV2A in complex with levetiracetam Method: EM (single particle) / Resolution: 2.58 Å 70564 9okh EMDB-70564, PDB-9okh: Cryo-EM structure of human SV2A in complex with UCBJ Method: EM (single particle) / Resolution: 2.39 Å 70565 9oki EMDB-70565, PDB-9oki: Cryo-EM structure of human SV2A in complex with UCBJ and UCB1244283 Method: EM (single particle) / Resolution: 2.67 Å 70566 9okj EMDB-70566, PDB-9okj: Cryo-EM structure of human SV2A in complex with padsevonil Method: EM (single particle) / Resolution: 2.68 Å 71812 9prs EMDB-71812, PDB-9prs: Cryo-EM structure of human SV2A in complex with Levetiracetam and UCB1244283 Method: EM (single particle) / Resolution: 3.03 Å
Chemicals	ChemComp, No image ChemComp-UKX: Unknown entry PDB-1cca: THE ASP-HIS-FE TRIAD OF CYTOCHROME C PEROXIDASE CONTROLS THE REDUCTION POTENTIAL, ELECTRONIC STRUCTURE, AND COUPLING OF THE TRYPTOPHAN FREE-RADICAL TO THE HEME PDB-1b1i: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN ChemComp, No image ChemComp-X3U: Unknown entry PDB-1b1j: CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN VARIANT H13A.
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / SLC transporter / SLC22 family / apo state / inhibitor / ligand binding