Studies on the mechanism of the catalytic superoxide decomposition by the nickel-based superoxide dismutase employing functional peptide-based model compounds

• Applicant: Professor Dr. Gerd Buntkowsky
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 243977495

The aim of the proposal is the investigation of the catalytic mechanism of Nickel superoxide dismutase (NiSOD) through the study of small peptide based model compounds by a combination of liquid-state and solid-state nuclear magnetic resonance spectroscopy, kinetic measurements and theoretical calculations. In preliminary works we were able to produce a stable structural model complex, where cyanide coordinates as substrate analogue in the active center of the NiSOD model peptides and to determine the structure of the cyanide adduct. The first focus of the project is the study to what extent specific mutations of these model peptides influence the catalytic activity or the position of the substrate analogue in the active site of the NiSOD model peptides. In contrast to the model peptides, which are trans-configured, the natural enzyme is in a cis- configuration. Therefore the second focus of the project is to study the effect of the trans/cis configuration on the catalytic activity of the models and the binding of cyanide as substrate analogue. The third part of the project studies the role and binding of functional water molecules in the active site of the model peptides. This is intended to clarify whether there are similarities to the catalytic behavior of other SOD classes.

• DFG Programme: Research Grants
• Participating Person: Dr. Daniel Tietze