Research
Our research focuses on the energy converting enzymes of bacterial respiratory chains, mainly on the proton pumping NADH:ubiquinone oxidoreductase, respiratory complex I, and the cytochrome bd ubiquinol oxidase.
Respiratory complex I couples the electron transfer from NADH to ubiquinone with the translocation of protons across the membrane. The structure of the complex from several sources was determined at molecular resolution by x-ray crystallography and cryo-electron microscopy. Complex I has a L-shaped appearance consisting of a peripheral arm made up by globular subunits and a membrane arm composed of polytopic subunits. The peripheral arm catalyzes electron transfer and the membrane arm proton translocation. We are working with the Escherichia coli complex I that is composed of 13 subunits resulting in a molecular mass of approximately 530 kDa. It contains one non-covalently bound flavin mononucleotide and nine iron-sulfur clusters as cofactors for electron transfer. The coupling of electron tranfer with proton translocation is still under debate. In humans a dysfunction of the complex is associated with several neurodegenerative diseases such as Parkinson’s disease.
Cytochrome bd ubiquinol oxidase uses the electron transfer from ubiquinol to oxygen to establish a proton gradient across the membrane by a vectorial mechanism. The enzyme complex consists of the major subunits CydA and B and, depending on the species, of one or two small proteins that are made up one single transmembranous helix called CydX and Y. The presence of either CydX alone or CydX and Y together is indicative for a different physiological role of the enzyme as an oxidase or a defense factor. Cytochrome bd ubiquinol oxidase contains two b- and one d-type hemes as cofactors. This enzyme is only present in bacteria some of which are pathogens. Thus, bd oxidase is a promising target to fight e.g. Vibrio cholera. As a curiosity, E. coli contains two bd oxidases that share a high structural similarity but which are produced under different growth conditions.