Binding of a single zinc ion to one subunit of copper-zinc superoxide dismutase apoprotein substantially influences the structure and stability of the entire homodimeric protein.

The thermodynamics of zinc binding to metal-free (apo) human and bovine copper-zinc superoxide dismutases (SOD1) were measured using isothermal titration calorimetry. The apparent thermodynamics of zinc binding to the apoproteins were favorable (Ka > 108 M-1), with an observed stoichiometry of one zinc per homodimer. The change in heat capacity for the one-zinc binding event was large and negative (approximately -650 cal mol-1 K-1), suggestive of significant structural changes to the protein upon zinc binding.

Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis.

Copper-zinc superoxide dismutase (CuZnSOD, SOD1 protein) is an abundant copper- and zinc-containing protein that is present in the cytosol, nucleus, peroxisomes, and mitochondrial intermembrane space of human cells. Its primary function is to act as an antioxidant enzyme, lowering the steady-state concentration of superoxide, but when mutated, it can also cause disease. Over 100 different mutations have been identified in the sod1 genes of patients diagnosed with the familial form of amyotrophic lateral sclerosis (fALS).

The perplexing role of copper-zinc superoxide dismutase in amyotrophic lateral sclerosis (Lou Gehrig's disease).

The existence of a link between some cases of familial amyotrophic lateral sclerosis (FALS) and copper-zinc superoxide dismutase (CuZnSOD) has been understood for almost a decade. However, beyond the fact that mutations in CuZnSOD cause FALS by a toxic gain of function, the mechanism whereby specific mutations in the protein structure result in development of the disease has remained almost a complete mystery to date. We have undertaken a critical survey of in vitro characteristics of over 30 of the 90 different CuZnSOD mutant proteins that are known to cause FALS in order to determine the differences that exist between mutant and wild-type properties.