How do reactive oxygen species affect the active sites of metalloproteins?

• Applicant: Professor Dr. Thomas Happe
• Co-Applicant: Professor Dr. Markus Reiher
• Subject Area: Biochemistry
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 210711264

With the emergence of an aerobic atmosphere, organisms were forced to develop strategies to deal with the deleterious effects of exposition to dioxygen (O2) and highly reactive O2 derivatives designated as reactive oxygen species (ROS). Several metalloproteins which contain transition metal complexes exhibit a high sensitivity against molecular O2. Mechanistic studies on the enzyme destruction are restricted to only a few examples like the proteins aconitase or the fumarate nitrate reductase regulator (FNR). Enzymes that contain more intricate metal complexes like nitrogenases and hydrogenase are also quickly destroyed by dioxygen but due to their complexity it is more challenging to obtain structural insights into their reactivity. Out of the three existing hydrogenase classes, [FeFe] hydrogenases exhibit the highest catalytical activity for hydrogen production but at the same time also the highest O2-sensitivity. In the presented project the O2 induced inactivation of the [FeFe] hydrogenase active site will be elucidated in a synergistic cooperation between theoretical and experimental scientists. A systematical approach to the general problem of oxygen induced inhibition requires a detailed theoretical understanding of the reaction events involved and the development of suitable computational methods that in concert with experimental verification opens the path to a tailored, more oxygen stable enzyme.

• DFG Programme: Research Grants
• International Connection: Switzerland