Combined spectroscopic/computational studies on Fe- and Mn-dependent superoxide dismutases: insights into second-sphere tuning of active site properties.
Superoxide dismutases (SODs) are metalloenzymes that protect aerobic organisms from oxidative damage mediated by the superoxide radical. While the Fe- and Mn-dependent SODs from E. coli possess virtually identical protein folds and active-site geometries, they are strictly metal specific. To explore the origin of this extraordinary metal-ion specificity and to elucidate the mechanisms by which these enzymes tune the geometric and electronic properties, and thus the reactivity, of their active-site metal ions, we utilized a combination of spectroscopic and computational methods to study the native enzymes, their metal-substituted derivatives, and several mutant proteins. Results from our research described in this Account reveal that second-sphere residues are critically involved in controlling both thermodynamic and kinetic properties of the Fe- and MnSOD active sites.
Jackson
Timothy A
TA
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Brunold
Thomas C
TC
D001665:Binding Sites; D002942:Circular Dichroism; D019295:Computational Biology; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D008345:Manganese / Q000737:chemistry*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism
D008345:Manganese; D007501:Iron; D013482:Superoxide Dismutase; D010100:Oxygen