An autocatalytic mechanism of protein nitrosylation

Andrey Nedospasov, Ruslan Rafikov, Natalya Beda, Evgeny Nudler

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13543-13548
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number25
DOIs
StatePublished - Dec 5 2000
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'An autocatalytic mechanism of protein nitrosylation'. Together they form a unique fingerprint.

Cite this