Two decades of new concepts in nitric oxide signaling: from the discovery of a gas messenger to the mediation of nonenzymatic posttranslational modifications.

For the past 20 years, nitric oxide (NO) has established itself as a gaseous free radical with crucial and unpredicted roles in a wide spectrum of biological functions and organisms. We present here a case whereby NO-mediated signaling can be broadly classified into classical (cGMP-mediated) and nonclassical, the latter mainly alluding to posttranslational modifications related to NO and its interaction with reactive groups in proteins.