As the most reactive member of nature standard stable of amino acids, cysteine is commonly tapped as a nucleophile in enzyme active sites. But cysteine reactivity also makes it uniquely susceptible to oxidation by reactive oxygen species in the cell. Some cysteine oxidations are simply the result of collateral damage incurred during times of oxidative stress. But others appear to be highly regulated smoke signals sent in the name of cellular communication. Oxidation of cysteine at sites other than the active site can also have complex regulatory functions says Cristina M. Furdui, an assistant professor of molecular medicine at Wake Forest University School of Medicine. In some kinase enzymes, for example, oxidation of a cysteine outside of the active site causes that oxidized cysteine to form a disulfide bond with a neighboring cysteine residue, she notes. Such disulfide bond formation can dramatically change the conformation of an enzyme, thereby altering its activity or targeting it for degradation. The list of proteins suspected to undergo cysteine oxidation has dramatically increased in recent months, thanks to the development of chemical tools for detecting and isolating the “gateway” cysteine oxidation: sulfenic acid.