Functional Implications of Heme-packing Motives in c-type Cytochromes

• Antragsteller: Professor Dr. Oliver Einsle
• Fachliche Zuordnung: Biochemie
• Förderung: Förderung von 2005 bis 2008
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5451573

Cytochromes are ubiquitous metalloproteins that play an essential role as redox enzymes or electron carriers in various metabolic pathways of organisms from all kingdoms of life. Among them, the subtype c is characterized by a covalent attachment of the cofactor heme to the protein chain. Cytochromes c often contain a large number of cofactors relative to the protein chain and play crucial roles in bacterial metabolic pathways, either as electron carriers or as redox enzymes. Hereby the arrangement of cofactors shows recurring motives of heme packing among different proteins, even in the absence of any detectable sequence homology. Being evolutionarily con-served, these packing motives are obviously of functional significance, but due to the strong cou-pling of multiple metal centers their properties are difficult to investigate using spectroscopic methods. In order to facilitate functional analyses we have set out to identify possible dihemic model systems for heme-heme interaction motives from the cytochrome-c-rich genome of Geobacter sulfurreducens or its relatives which are accessible to mutational studies and have interpretable spectroscopic properties. We have obtained a first model system, DHC2, determined its crystal structure and initiated spectroscopic analyses. Here we propose to identify and characterize further suitable model proteins and analyze their properties in a systematic, mutational study correlating spectroscopy, electrochemistry and crystallographic analysis. From simple model systems we want to develop a fundamental understanding of heme interaction and subsequently transfer this knowl-edge to larger and more complex proteins.

• DFG-Verfahren: Sachbeihilfen