New Nitric Oxide Messenger

Nitric oxide mediates myriad physiological processes, including blood vessel dilation and immune response. Though most NO signaling relies on the messenger molecule guanosine 3′,5′-cyclic monophosphate (cGMP), NO sometimes exerts its effects by other pathways, not all of which are completely understood. Now, Takaaki Akaike of Kumamoto University, in Japan, and colleagues report 8-nitro-cGMP (shown), a newly confirmed offshoot of cellular NO production (Nat. Chem. Biol., DOI: 10.1038/nchembio.2007.33). Despite a strong resemblance to cGMP, 8-nitro-cGMP has unique signaling roles because the NO₂ group confers distinct properties. For example, the electron-poor molecule reacts with the thiol in glutathione and in a redox-sensor signaling protein. These interactions swap the NO₂ group for an SH group, tagging the substrates with cGMP. This reaction is a novel post-translational modification the researchers call S-guanylation. The team thinks that its discovery further illuminates the downstream effects of NO and could be relevant to studies of NO-linked biological responses and diseases.