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Publication Abstract from PubMed

In eukaryotes, the bimetallic Cu/Zn superoxide dismutase (SOD) enzymes play important roles in the biology of reactive oxygen species by disproportionating superoxide anion. Recently, we reported that the fungal pathogen Candida albicans expresses a novel Cu-only SOD known as SOD5, that lacks the Zn cofactor and electrostatic loop (ESL) domain of Cu/Zn SODs for substrate guidance. Despite these abnormalities, C. albicans SOD5 can disproportionate superoxide at rates limited only by diffusion. Here we demonstrate that this curious Cu-only SOD occurs throughout the fungal kingdom as well as in phylogenetically distant oomycetes or pseudofungi species. It is the only form of extracellular SOD in fungi and oomycetes, in stark contrast to the extracellular Cu/Zn SODs of plants and animals. Through structural biology and biochemical approaches we demonstrate that these Cu-only SODs have evolved with a specialized active site consisting of two highly conserved residues equivalent to SOD5 E110 and D113. The equivalent positions are Zn binding ligands in Cu/Zn SODs and have evolved in Cu-only SODs to control catalysis and Cu binding in lieu of Zn and the ESL. Similar to the Zn ion in Cu/Zn SODs, SOD5 E110 helps orients a key Cu coordinating histidine and extends the pH range of enzyme catalysis. SOD5 D113 connects to the active site in a manner similar to that of the ESL in Cu/Zn SODs and assists in Cu cofactor binding. Cu-only SODs are virulence factors for certain fungal pathogens; thus this unique active site may be a target for future anti-fungal strategies.

The Phylogeny and Active Site Design of Eukaryotic Cu-only Superoxide Dismutases.,Peterson RL, Galaleldeen A, Villarreal J, Taylor AB, Cabelli DE, Hart PJ, Culotta VC J Biol Chem. 2016 Aug 17. pii: jbc.M116.748251. PMID:27535222^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.