From microbiology to cancer biology: the Rid protein family prevents cellular damage caused by endogenously generated reactive nitrogen species

Mol Microbiol. 2015 Apr;96(2):211-9. doi: 10.1111/mmi.12945. Epub 2015 Feb 26.


The Rid family of proteins is highly conserved and broadly distributed throughout the domains of life. Genetic and biochemical studies, primarily in Salmonella enterica, have defined a role for RidA in responding to endogenously generated reactive metabolites. The data show that 2-aminoacrylate (2AA), a reactive enamine intermediate generated by some pyridoxal 5'-phosphate-dependent enzymes, accumulates in the absence of RidA. The accumulation of 2AA leads to covalent modification and inactivation of several enzymes involved in essential metabolic processes. This review describes the 2AA hydrolyzing activity of RidA and the effect of this biochemical activity on the metabolic network, which impacts organism fitness. The reported activity of RidA and the consequences encountered in vivo when RidA is absent have challenged fundamental assumptions in enzymology, biochemistry and cell metabolism regarding the fate of transiently generated reactive enamine intermediates. The current understanding of RidA in Salmonella and the broad distribution of Rid family proteins provide exciting opportunities for future studies to define metabolic roles of Rid family members from microbes to man.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acrylates / metabolism
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Humans
  • Multigene Family*
  • Neoplasms / metabolism*
  • Reactive Nitrogen Species / metabolism*
  • Salmonella enterica / genetics
  • Salmonella enterica / metabolism*


  • Acrylates
  • Bacterial Proteins
  • Reactive Nitrogen Species
  • acrylic acid