The overall goal of this project is to understand the structure and function of diiron-oxo sites in proteins. Two such proteins have been chosen as the focus of investigations: hemerythrin (and myohemerythrin), an O 2-carrying protein from marine invertebrates, rubreythrin, a protein of unknown biological function form anaerobic sulfate-reducing bacteria, and bacterioferritin,and iron storage protein found in several bacteria. Since the structure and function of hemerythrin is already known in some detail, the proposed research aims to examine a relatively neglected but crucial aspect, namely, the roles of conserved residues lining the O2 binding pocket in modulation of O2 affinity and in protection of the diiron site against autoxidation. Rubrerythrin is a diiron-oxo from the anaerobic sulfate-reducing bacterium, Desulfovibrio vulgaris. The major unsolved problem for this protein is biological function. The results obtained during the previous projects period show that the diiron domain of the rubreythrin subunit a strong structural resemblance to the subunits of the iron storage proteins, ferritin and bacterioferritin. The results strongly suggest that rubreythrin's biological function involves iron metabolism, perhaps connected to oxygen tolerance of the bacteria. A systematic investigation of the function of rubrerythrin both in vitro and in vivo is proposed. Since many infections bacteria have developed mechanisms for obtaining iron from their host, an understanding of iron metabolism in the bacteria mentioned above will increase our understanding of pathogenesis. This includes anaerobic sulfate-reducing bacteria, which have been found in the human gut. A health-related goal of understanding the dioxygen- carrying mechanism of hemerythrin is to develop this protein for use in blood substitutes.
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