Oxygen is required for the L-cysteine-mediated decomposition of protein-bound dinitrosyl-iron complexes.

Increasing evidence suggests that iron-sulfur proteins are the primary targets of nitric oxide (NO). Exposure of Escherichia coli cells to NO readily converts iron-sulfur proteins to protein-bound dinitrosyl-iron complexes (DNICs). Although the protein-bound DNICs are stable in vitro under aerobic or anaerobic conditions, they are efficiently repaired in aerobically growing E. coli cells even without new protein synthesis. The cellular repair mechanism for the NO-modified iron-sulfur proteins remains largely elusive. Here we report that, unlike aerobically growing E. coli cells, starved E. coli cells fail to reactivate the NO-modified iron-sulfur proteins. Significantly, the addition of L-cysteine, but not other related biological thiols, results in decomposition of the protein-bound DNICs in starved E. coli cells and in cell extracts under aerobic conditions. However, under anaerobic conditions, L-cysteine has little or no effect on the protein-bound DNICs in starved E. coli cells or in vitro, suggesting that oxygen is required for the L-cysteine-mediated decomposition of the protein-bound DNICs. Additional studies reveal that L-cysteine is able to release the DNIC from the protein and bind to it, and the L-cysteine-bound DNICs are rapidly disrupted by oxygen, resulting in the eventual decomposition of the protein-bound DNICs under aerobic conditions.