Extracellular superoxide dismutase: structural and functional considerations of a protein shaped by two different...

The effects of reactive oxygen species are detrimental and can cause damage to DNA, protein, and lipids. Hence, the etiology of a large range of diseases resides in the generation of excess reactive oxygen species. However, these species are also involved in the maintenance of physiological functions. In tissues, it is therefore essential to maintain a steady-state level of antioxidant activity to allow both for the physiological functions of reactive oxygen species to proceed and at the same time preventing tissue damage. Extracellular superoxide dismutase (EC-SOD) is the only extracellular scavenger of the superoxide radical. The reactivity of superoxide is promiscuous and it is crucial that EC-SOD is positioned at the site of superoxide production to prevent adventitious reactions. It is therefore likely beneficial to have mechanisms for regulating the EC-SOD tissue distribution and enzymatic activity. The modular architecture of EC-SOD, encompassing three functional regions, is an ideal construction to generate diversity. By intracellular proteolytic processing and generation of active and inactive molecules, EC-SOD represents a flexible protein with the capacity to fine-tune the tissue localization and the antioxidant level in the extracellular space. The present review will address the function and activity of the separate regions of EC-SOD.