FeSuperoxide Dismutase

Abstract

Iron‐containing superoxide dismutases (FeSOD) are generally dimers of identical 21‐kDa monomers, each of which contains a single active site. Each active site binds one Fe ion with roughly trigonal bipyramidal geometry, employing two His and an Asp − residue as equatorial ligands, and one more His and a coordinated solvent as axial ligands. In the course of the catalytic cycle, the Fe alternates between the +3 and +2 states, and the coordinated solvent is believed to alternate between OH − and H 2 O, in concert. Activity is inhibited by coordination of F − , N 3 − , or OH − to the oxidized state. Decreased activity at high pH reflects the latter in addition to ionization of the conserved Tyr34 in the reduced state of the enzyme at pH 8.5. Despite strong structural homologies with the manganese containing superoxide dismutases (MnSODs), many FeSODs are inactive when reconstituted with Mn, and in the case of Escherichia coli SODs this appears to reflect, at least in part, very large differences in the reduction potentials produced by the two different SOD proteins, either Fe or Mn. Subtle changes in strengths of key active site H‐bonds could differently tune the p K s of the coordinated solvent molecule, whose participation in proton‐coupled electron transfer would in turn cause these differences to contribute to different reduction potentials, in the two proteins. Thus, SOD suggests that H‐bond mediated tuning of the protonation state and p K s of redox‐coupled coordinated solvents may serve as a means of tuning the E m in other cases as well.

Systematic structural studies of iron superoxide dismutases from human parasites and a statistical coupling analysis of metal binding specificity

“…Furthemore, there are no significant differences between the three structures reported here. All present the five ligands (His28, His76, His165, Asp161 and a water molecule) spatially arranged in a trigonal bipyramid around the iron atom 26. Beyond the ligands themselves, the active site neighbourhood also shows the well‐conserved hydrogen bonding network involving Trp125, Gln72, Tyr36, His32, and Tyr168 from the vicinal subunit 59.…”

“…and in several bacterial genomes,19, 20 and present a distinct four‐helix antiparallel bundle topology 21, 22. The different SOD types posses a widespread distribution in both eukaryotic and prokaryotic cells, appearing either in the cytosol, periplasm or compartmentalized in organelles such as mitochondria and chloroplasts 15, 23–27. For instance, while the protozoan parasites P. falciparum , T. cruzi , and T. brucei present only different isoforms of the iron‐containing SOD, distributed in the cytosol, glycosomes, and mitochondria,11, 28–32 their host human cells possess a mitochondrial MnSOD33 and a cytosolic Cu‐ZnSOD.…”

The effectiveness of Oral Superoxide Dismutase (SOD) on total antioxidant status, Trans Epidermal Water Loss (TEWL) and sebum concentration in photo aging skin

“…ROS accumulation plays an important role in photoaging where antioxidant enzyme significantly declines on the corneum layer and increase the concentration of protein oxidation in the upper dermis (Miller, 2011). Our study showed SOD increased TAS value and sebum concentration while decreasing in TEWL.…”

Exploring the selectivity of metal ions in the active site of the enzyme superoxide dismutase (SOD) using site-directed mutagenesis

“…Each subunit is composed of two domains: an α-helical N-terminal domain and a mixed α/β C-terminal domain. [43][44][45][46] The subunits have a single metal ion in the active site. The metal center is bound by equivalent residues, coordinated in trigonal bipiramidal geometry; two histidines and an aspartate residue occupy the equatorial plane with a histidine residue and a solvent molecule (water or hydroxide) occupying the axial positions.…”

“…Group 2; SODs that have an intervening fragment containing a short helix H2 between the two helices H1 and H3. (e.g., Fe-SODs from Escherichia coli 44 , cambialistic SOD from Porphyromonas gingivalis 39 ). Group 3; SODs with longer loop between H1 and H2 (e.g., Fe-SOD from Aquifex pyrophilus 134 ).…”