Focussing on water-protein coupled motions
It is nowadays widely accepted that the water in complex biological processes plays a key role, however it is still not fully understood, due to the technical challenges associated with probing real-time changes in water dynamics during reaction. By integrating hard-core experimental technologies, such as terahertz spectroscopy, to X-ray absorption and analyses the researchers measured changes in the coupled protein-water motions during enzymatic reaction. In addition, by means of molecular dynamics simulations, they could provide atomistic detail of the underlying mechanism. The investigated enzyme belongs to the family of the metalloproteinases, involved in the degradation of extracellular matrix proteins.
A new biological phenomenon
Using this integrated approach, the authors revealed a new biological phenomenon, in which water motions do not follow the classical enzymatic theory, but generate long-lasting protein-water motions that last longer than a single catalytic cycle. They observe the formation of a “hydrogen funnel” towards the molecular recognition site. The motions of the water are then adapted to the motions of the substrate which seems to be critical for binding, explains Prof. Dr. Martina Havenith-Newen. Furthermore, this new phenomenon has been shown to depend on the binding partner, being the optimized molecular architecture of a binding partner critical for water-mediated effective binding. To conclude, altogether these observations revise the classical theory of enzymatic catalysis by including long-lasting protein-water coupled motions into models of functional catalysis.
Source: Ruhr University Bochum