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Biological Chemistry

New Nitric Oxide Messenger

October 8, 2007 | A version of this story appeared in Volume 85, Issue 41

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.

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