Anshumali Mittal

Abstract Brivaracetam (BRV) and levetiracetam (LEV) are antiseizure medications (ASMs) that target synaptic vesicle protein 2A (SV2A), while UCB1244283 acts as a positive allosteric modulator of these medications. The SV2A-BRV-UCB1244283 complex reveals how UCB1244283 allosterically enhances BRV binding by occupying an allosteric site near the primary binding site, preventing BRV dissociation.

Correction to: Nature Structural & Molecular Biology https://doi.org/10.1038/s41594-024-01335-1, published online 19 June 2024. In the version of the article initially published, the text “A portion of this research was supported by NIH grant no. R24GM154185 and performed at the Pacific Northwest Center for Cryo-EM (PNCC) with assistance from Marcelo De Farias and Janette Myers” was omitted from the Acknowledgements and has now been added to the HTML and PDF versions of the article.

Abstract 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.