期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2000
卷号：97
期号：25
页码：13543-13548
DOI：10.1073/pnas.250398197
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Nitros(yl)ation is a widespread protein modification that occurs during many physiological and pathological processes. It can alter both the activity and function of a protein. Nitric oxide (*NO) has been implicated in this process, but its mechanism remained uncertain. *NO is unable to react with nucleophiles under oxygen-free conditions, suggesting that its higher oxides, such as N2O3, were actually nitrosylating agents. However, low concentrations and short lifespans of these species in vivo raise the question of how they could efficiently locate target proteins. Here we demonstrate that at physiological concentrations of *NO, N2O3 forms inside protein-hydrophobic cores and causes nitrosylation within the protein interior. This mechanism of protein modification has not been characterized, because all previously described mechanisms (e.g., phosphorylation, acetylation, ADP-ribosylation, etc.) occur via attack on a protein by an external modification agent. Oxidation of *NO to N2O3 is facilitated by micellar catalysis, which is mediated by the hydrophobic phase of proteins. Thus, a target protein seems to be a catalyst of its own nitrosylation. One of the applications of this finding, as we report here, is the design of specific hydrophobic compounds whose cooperation with *NO and O2 allows the rapid inactivation of target enzymes to occur.
