Decoding Fundamental Principles in Enzymatic Catalysis

Enzymes can accelerate otherwise slow chemical reactions up to several billion fold.

Harnessing of this “super-power” in a rational manner would have enormous implications for biotechnological applications. This requires knowledge of the fundamental principles at play.

As an example, the development of the polymerase chain reaction (PCR) was, in part, dependent on the discovery of thermostable enzymes.

Here we will push the limits of the research field forward by decoding fundamental principles of enzymatic catalysis that remains enigmatic, including: (1) the evolutionary origin of enzymatic substrate specificity, (2) the evolutionary origin of enzyme dynamics and (3) spatial and dynamic reorganisation of an enzymatic active site.

We will develop a concept that is focused on the enzyme adenylate kinase (AK) isolated from the three domains of life, i.e: bacterial, archaeal and eukaryotic organisms. Comparative analysis between these domains will enable novel findings through evolutionary linkages. Experimentally, we will employ an integrated approach that is rooted in biophysics and structural biology.

The main techniques will be NMR spectroscopy, x-ray crystallography and computational structural biology together with biochemical and biophysical methodology.

The proposed research is designed for four years and will be performed by members of my group in collaboration with both national and international research labs.