The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa

Abstract

2-aminoacrylate (2AA) is a reactive metabolite formed as an intermediate in various enzymatic reactions. In the absence of RidA, this metabolite can persist in vivo where it attacks and inactivates specific PLP-dependent enzymes, causing metabolic defects and organism-specific phenotypes.

DadY (PA5303) is required for fitness of Pseudomonas aeruginosa when growth is dependent on alanine catabolism

“…Proteins in the RidA and Rid1-3 subfamilies, including RutC proteins, contain the relevant arginine residue, and all such proteins that have been assayed to date have some imine/enamine deaminase activity in vitro [18][19][20][21][22][23][24][25][26][27][28][29]. Significantly, the deaminase reaction catalyzed by Rid proteins assessed thus far can also be carried out spontaneously by solvent water, suggesting that these proteins simply accelerate a reaction that can occur in their absence [19][20][21][22][29][30][31]. Members of the RidA subfamily have been assigned a role in ameliorating 2-aminoacrylate stress in a paradigm that has been well established in several bacterial species, yeast, and higherorder eukaryotes [2,[23][24][25][30][31][32][33][34].…”

“…Significantly, the deaminase reaction catalyzed by Rid proteins assessed thus far can also be carried out spontaneously by solvent water, suggesting that these proteins simply accelerate a reaction that can occur in their absence [19][20][21][22][29][30][31]. Members of the RidA subfamily have been assigned a role in ameliorating 2-aminoacrylate stress in a paradigm that has been well established in several bacterial species, yeast, and higherorder eukaryotes [2,[23][24][25][30][31][32][33][34]. The deaminase activity of proteins in the other Rid subfamilies, except for RutC from Escherichia coli [22], has not been placed in a physiological context [15,20,21,24,35].…”