STRUCTURAL CHARACTERIZATION OF RUBRERYTHRIN, A KEY COMPONENT IN ENTAMOEBA HISTOLYTICA RESISTANCE TO OXIDATIVE STRESS

Entamoeba histolytica (Eh) is the parasite that causes amoebic dysentery, a disease that is mainly spread in developing countries1. Eh can live in the gut, an anaerobic environment where its metabolism has evolved. During tissue invasion, E. histolytica must withstand the oxidative burst from the host's immune system. It accomplishes this by utilizing a unique arsenal of redox proteins, many of which were acquired from prokaryotes via horizontal gene transfer².
One of the key enzymes modulated during oxidative stress is Rubrerythrin (Rr)³. All Rubrerythrins structurally characterized to date are from prokaryotic sources and function as homodimers. These enzymes catalyze the two-electron reduction of hydrogen peroxide to water. This reaction occurs at a di-iron active site within one subunit, which receives electrons from a rubredoxin-like Fe(Cys)₄ center located in the adjacent subunit, approximately 12 Å away.
In this study, we present the first X-ray crystal structure of a eukaryotic Rubrerythrin, that of E. histolytica, determined at 2.4 Å resolution. Our results reveal a significant deviation from the established structural motif. Unlike the previously reported dimeric structures from organisms like Desulfovibrio vulgaris ^{4 5} and Pyrococcus furiosus ⁶, the E. histolytica Rubrerythrin is organized as a tetramer. This novel quaternary structure raises intriguing questions about its potential implications for the enzyme's physiological function and its role in the parasite's defense against oxidative stress.

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