Unravelling the Enantioselective Mechanism of Benzylsuccinate Synthase - finally published

After 17 months of reviewing struggle, we finally managed to publish our paper in Biochemistry.

The paper describes a very complex mechanism of benzylsuccinate synthase studied by QM:MM and microkinetic analysis that is able to predict enantiospecificity of the enzyme.

What is interesting here is that it is not (only) the binding pose of the substrate that determines the final product's chiral structure, but also kinetics. The pathway leading to the wrong enantiomer is simply slower. Furthermore, when the fumarate is bound in the "wrong" position, the chance of forming a C-C bond at the carbon leading to a kinetic dead end is higher. So, in here, you would not be able to guess the right product solely by docking or even by the calculation of the DG of binding. You need to understand the whole reaction mechanism. The paper is the main achievement of the Beethoven Life Project.