Cysteine is the most intrinsically nucleophilic amino acid in proteins, but the absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here, a proteomics method to quantitatively profile the intrinsic reactivity of cysteine residues directly in native biological systems is described. Hyper-reactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotes that is shown to be required for yeast viability and involved in iron–sulphur protein biogenesis.
- Eranthie Weerapana
- Chu Wang
- Benjamin F. Cravatt
