Superoxide (O2–) is a highly toxic species derived from the one electron reduction of dioxygen. To avoid oxidative damage induced by O2– and the production of toxic down-stream reduction products of O2–organisms have evolved pathways to rapidly degrade low concentrations of cellular superoxide. The most commonly employed pathways are the superoxide dismutases (SODs), which fall into five classes based on the metal(s) contained at their active-site. Nickel superoxide dismutase (NiSOD) is a relatively recently discovered SOD found primarily in aquatic and soli bacteria, and represents the most widely expressed SOD on Earth. Found as a homohexamer in solution, each NiSOD monomer contains a mononuclear nickel-site that cycles between formal Ni2+ and Ni3+ oxidation states during the disproportionation of O2– into O2 and H2O2. In its Ni2+ oxidation state, nickel is ligated in a nearly square-planar N2S2 coordination environment with ligands derived from cysteinate sulfur atoms, the N-terminal amine nitrogen and an amidates nitrogen. Oxidation to Ni3+ induces the coordination of an N-terminal histidine imidazole nitrogen to the axial nickel position, forming a square pyramidal structure. An additional structural feature observed in NiSOD is the observation that the coordinated S-atoms undergo reversible protonation events in response to enzymatic oxidation and reduction. In this work we will probe the mechanism of superoxide disprotportionation using high-level electronic structure calculations of the NiSOD active-site. The proposed mechanism will be supported through mechanistic studies of the employing the itself. It will be shown that the most viable pathway for superoxide disproportionation likely involves an inner-sphere O2– reduction mechanism.

Probing the mechanism of superoxide disproportionation by nickel-containing superoxide dismutase through experimental and computational studies

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.