Proteolysis induced by metal-catalyzed oxidation

Abstract

Many enzymes are now known to be subject to site-specific, covalent modification mediated by activated oxygen species. Oxidatively modified enzymes generally lose catalytic activity, gain carbonyl groups in their side chains, and become susceptible to proteolytic degradation. Thus, oxidative modification is one of the covalent alterations which marks proteins for degradation. This degradation is mediated by specific intracellular proteinases which degrade only the modified proteins. One can then view the turnover as occurring in two distinct steps: 1) Metal-catalyzed oxidative modification marks the protein for degradation. 2) The marked protein is degraded by a specific proteinase. Utilizing a model metal-catalyzed oxidation system (ascorbate/iron/oxygen) studies on bacterial glutamine synthetase revealed several functional and structural changes. Analysis of the time courses of these changes established correlations between specific structural alterations and increased susceptibility to proteolytic degradation.