Avoiding high-valent iron intermediates: superoxide reductase and rubrerythrin

Area of Science:

• Biochemistry
• Enzymology
• Oxidative Stress

Background:

• Fenton-type reactions generate highly oxidizing species (e.g., hydroxyl radical) from ferrous ions and hydrogen peroxide.
• Uncontrolled intracellular Fenton chemistry can be lethal, necessitating cellular defense mechanisms.
• Superoxide reductase (SOR) and rubrerythrin (Rbr) are non-heme iron enzymes found in anaerobic organisms that scavenge reactive oxygen species.

Purpose of the Study:

• To investigate the roles of superoxide reductase (SOR) and rubrerythrin (Rbr) in managing intracellular Fenton-type reactions.
• To understand how these enzymes protect against oxidative damage initiated by hydrogen peroxide and ferrous ions.
• To elucidate the mechanisms by which SOR and Rbr mitigate the effects of reactive oxygen species.

Main Methods:

• Comparative analysis of SOR and Rbr enzyme structures and active sites.
• Investigation of enzyme kinetics with hydrogen peroxide.
• Assessment of enzyme function in scavenging reactive oxygen species and mitigating Fenton-type reactions.

Main Results:

• SOR and Rbr contain non-heme iron active sites with specific protein ligand coordination (His, Glu, Cys).
• SOR's mononuclear site rapidly expels peroxide, while Rbr's diferrous site reacts faster with hydrogen peroxide.
• Rbr can divert Fenton-type reactions to water, and aromatic residues may act as radical sinks, protecting active sites from damage.

Conclusions:

• SOR and Rbr are crucial enzymes for controlling intracellular Fenton-type chemistry in air-sensitive organisms.
• These enzymes employ distinct mechanisms to neutralize hydrogen peroxide and protect against oxidative damage.
• Fenton-initiated damage to these iron active sites is relevant under severe oxidative stress conditions.