Eukaryotic copper-only superoxide dismutases (SODs): A new class of SOD enzymes and SOD-like protein domains

• Published in: The Journal of biological chemistry Vol. 293; no. 13; pp. 4636 - 4643
• Main Authors: Robinett, Natalie G., Peterson, Ryan L., Culotta, Valeria C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.03.2018; American Society for Biochemistry and Molecular Biology
• Subjects: copper; Copper - chemistry; Copper - metabolism; Fungal Proteins - chemistry; Fungal Proteins - classification; Fungal Proteins - metabolism; Fungi - enzymology; metalloprotein; Metalloproteins - chemistry; Metalloproteins - classification; Metalloproteins - metabolism; Minireviews; Mycobacterium - enzymology; Oomycetes - enzymology; Periplasmic Proteins - chemistry; Periplasmic Proteins - classification; Periplasmic Proteins - metabolism; redox signaling; superoxide dismutase (SOD); Superoxide Dismutase - chemistry; Superoxide Dismutase - classification; Superoxide Dismutase - metabolism; superoxide ion; Zinc - chemistry; Zinc - metabolism; superoxide ion; metalloprotein; copper; redox signaling; superoxide dismutase (SOD)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.TM117.000182

The copper-containing superoxide dismutases (SODs) represent a large family of enzymes that participate in the metabolism of reactive oxygen species by disproportionating superoxide anion radical to oxygen and hydrogen peroxide. Catalysis is driven by the redox-active copper ion, and in most cases, SODs also harbor a zinc at the active site that enhances copper catalysis and stabilizes the protein. Such bimetallic Cu,Zn-SODs are widespread, from the periplasm of bacteria to virtually every organelle in the human cell. However, a new class of copper-containing SODs has recently emerged that function without zinc. These copper-only enzymes serve as extracellular SODs in specific bacteria (i.e. Mycobacteria), throughout the fungal kingdom, and in the fungus-like oomycetes. The eukaryotic copper-only SODs are particularly unique in that they lack an electrostatic loop for substrate guidance and have an unusual open-access copper site, yet they can still react with superoxide at rates limited only by diffusion. Copper-only SOD sequences similar to those seen in fungi and oomycetes are also found in the animal kingdom, but rather than single-domain enzymes, they appear as tandem repeats in large polypeptides we refer to as CSRPs (copper-only SOD-repeat proteins). Here, we compare and contrast the Cu,Zn versus copper-only SODs and discuss the evolution of copper-only SOD protein domains in animals and fungi.