Structural studies and electron transfer on Cytochrome c Oxidases

ALEJANDRO J, VILA

Montevideo

Congreso; V International Conference on Peroxynitrite and Reactive Nitrogen Species “Free Radicals in Montevideo; 2007

Cytochrome c oxidases catalyze O2 reduction by coupling electron transfer with transmembrane proton pumping. The electron entry port in most oxidases is a dinuclear copper center (CuA) located in a highly conserved soluble subunit. This metal site is optimally design for efficient intra- and intermolecular electron transfer events. In order to be efficient, this metal site should be able to shutlle electrons with a low reorganization energy. We have studied the backbone mobility features in the soluble subunit of T.thermophilus ba3 oxidase. This protein is very rigid along different timescales, even in protein loops that provide the anchoring points for the copper site. This can be related to the functional needs of this center. We have also studied by paramagnetic NMR the electron spin distribution between the two copper ions and how this electrons are delocalized onto the metal ligands. The structure of the CuA center needs to be properly built. It has been proposed that Sco1, a protein conserved in many organisms, is responsible of the assembly of the CuA site. Indeed, pathogenic mutations in Sco1 have been identified in several cases of fatal infantile encephalopathy, which determine the correct assembly of the metal centers in cytochrome oxidase. We have also studied Sco1 from T.thermophilus in order to clarify its role in metal cofactor assembly in terminal oxidases.