Nitric oxide (NO) is an important signalling molecule in biological systems, but it is unclear exactly how it interacts with some metalloproteins. Now, a collection of articles in this issue reveal how NO binds to proteins containing type-1 copper sites.
Nitric oxide (NO) has important functions in all forms of life and serves, for example, as a signalling molecule in mammals. Now, two complementary studies have uncovered how NO binds to blue copper proteins. This research suggests a mechanism by which NO could regulate the activity of blue copper proteins involved in denitrification.
NO participates in numerous physiological processes of which many involve the reaction of
NOwith metalloenzymes to form a metal–nitrosyl (M–NO). Now, addition of NOto models of type 1 Cu sites has provided a fully characterized S-nitrosothiol adduct, [CuI](κ1-N(O)SR), that reversibly loses NOupon purging with an inert gas. These findings suggest a new motif for reversible binding of nitric oxide at bioinorganic metal centres.
S-Nitrosylation has emerged as an important pathway for dynamic post-translational regulation of many classes of proteins. Now, the reversible insertion of NO into a copper–thiolate bond has been observed under physiologically relevant conditions using an engineered azurin. DFT calculation indicates that the reaction proceeds via a radical combination mechanism.