State of the art  

Controlling the catalytic activity of enzymes is one of the central goals in biocatalysis. Nature has designed a large variety of control mechanisms of impressive robustness. These systems often comprise a combination of sensory and catalytic modules, the function of which relies on concerted conformational changes induced by the sensor. From an experimental point of view, systems using sensors for light, voltage, or redox potential are most attractive, because they represent well-defined and easy-to-control input signals.

In this research field, we will study enzyme complexes consisting of a catalytic and a light- or voltage-sensor module to gain insights into the structural and dynamic aspects involved in these regulation systems. In particular, we will use phosphatases and adenylate cyclases (ACs), which catalyse the production of phosphatidyl-inositol-biphosphate (PIP2 from PIP3) and cyclic-adenosyl monophosphate (cAMP) from ATP, respectively. The sensor modules of these systems are either membrane-associated blue-light receptors (BLUF), membrane-inserted green-light receptors (rhodopsins), or voltage sensors. Even though a substantial amount of information is already known for the individual modules, the properties of the coupled systems are largely unknown.

Our research will therefore concentrate on the spatial and dynamic properties of the conformational coupling process between sensor and catalyst, which will take advantage of the fact that enzymatic activity can most conveniently be triggered and synchronized by short light pulses or voltage steps. To understand the conformational fine-tuning of catalytically active sites, these investigations require close collaboration between researchers in spectroscopy, electrophysiology and structural biology.   

Research goals  

The goal of the project is the understanding of enzymes & catalysts that are modulated by light or membrane voltage, beginning from the sensing of the light absorption or voltage jump via early conformational changes in the chromophore domains, towards enzyme activation, adaptation and silencing. The five-year goal is to tailor new enzymes with specific chromophore or voltage sensor properties, and with catalytic activity that will be applicable to medical science and biotechnology (Optogenetic Technology).