Superoxide dismutases: active sites that save, but a protein that kills.
Protection from oxidative damage is sufficiently important that biology has evolved three independent enzymes for hastening superoxide dismutation: the Cu- and Zn-containing superoxide dismutases (Cu,Zn-SODs), the SODs that are specific for Fe or Mn or function with either of the two (Fe-SODs, Mn-SODs or Fe/Mn-SODs), and the SODs that use Ni (Ni-SODs). Despite the overwhelming similarities between the active sites of Fe-SOD and Mn-SOD, the mechanisms and redox tuning of these two sites appear to incorporate crucial differences consistent with the differences between Fe3+/2+ and Mn3+/2+. Ni-SOD is revealed by spectroscopy to employ completely different ligation to that of the other SODs while nonetheless incorporating a device also found in Cu,Zn-SOD. Finally, the protein of human Cu,Zn-SOD appears to be an important contributor to the development of amyotrophic lateral sclerosis, possibly because of its propensity for extended beta-sheet formation.
Miller
Anne-Frances
AF
Department of Chemistry, University of Kentucky, Lexington KY, 40506-0055, USA. afm@uky.edu
D001665:Binding Sites; D018384:Oxidative Stress; D040681:Structural Homology, Protein; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism*
D013482:Superoxide Dismutase