Sidec AB has together with UCB published the first direct structural evidence of the molecular mechanism of the Synaptic Vesicle protein 2A (SV2A) in mouse brain tissue. SV2A is the unique brain-binding site of the second generation anti-epileptic drug levetiracetam (LEV; Keppra® is a trademark of UCB). The result shows the first direct structural proof of the "alternating access model" that has been proposed for the MFS class of transporter proteins. The "alternating access model" postulates that the trans-membrane MFS class proteins can exist in two different conformations; as a valve that can be open to either side of the membrane. Prior to this Protein TomographyTM study, great efforts were made to prove this mechanism both by x-ray crystallography and indirectly by site directed mutagenesis.
"Obtaining structures of trans-membrane proteins is notoriously difficult, and the success of such endeavours is difficult to predict. This study demonstrates that Protein TomographyTM is well adopted to study structure, function and flexibility of trans-membrane proteins." says Anders Åberg, CSO at Sidec.
The publication is available on-line in the journal Biochemical and Biophysical Research Communications, August 7, 2008. Visualization of SV2A conformations in situ by the use of Protein Tomography