Crystallographic Investigations of Respiratory Proteins

All organisms require a respiratory process to produce energy. In eukaryotes, this process occurs in the mitochondria, and requires a respiratory chain of four integral membrane proteins as well as a membrane-soluble quinone pool and cytochrome c. The respiratory proteins transfer electrons to oxygen as the terminal electron acceptor with the electron transfer coupled to the translocation of protons across the mitochondrial membrane. Not all organisms use oxygen as the terminal electron acceptor of their electron transport chain. One of the more common alternative electron acceptors is fumarate, but other common electron acceptors include nitrogen-containing compounds, the transformation of which represents an important step in the biological nitrogen cycle. This thesis discusses the structural investigations of proteins involved in diverse respiratory processes. The crystal structure of the Escherichia coli fumarate reductase, an integral-membrane enzyme complex involved in anaerobic respiration with fumarate as the terminal electron acceptor, has been solved. This structure both suggests the mechanism of the terminal step of anaerobic fumarate respiration and gives a model for the function of the homologous protein succinate dehydrogenase from mitochondrial respiration. The crystal structure of cytochrome c554 from the chemoautotrophic nitrifer Nitrosomonas europaea shows a heme-packing motif that may be important in respiratory pathways that require the simultaneous transfer of multiple electrons.