L‐2,3‐diaminopropionate generates diverse metabolic stresses in <i>Salmonella enterica</i>

Ernst, Dustin C.; Anderson, Mary E.; Downs, Diana M.

doi:10.1111/mmi.13384

Cited by 23 publications

(18 citation statements)

References 57 publications

(91 reference statements)

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“…Growth defects of a ridA mutant have been attributed to the accumulation of 2-aminoacrylate in vivo [ 6 , 19 – 21 , 41 ]. The standard in vitro assay for RidA activity uses a PLP-dependent dehydratase to generate 2-aminoacrylate in situ .…”

Section: Resultsmentioning

confidence: 99%

Members of the Rid protein family have broad imine deaminase activity and can accelerate the Pseudomonas aeruginosa D-arginine dehydrogenase (DauA) reaction in vitro

Hodge‐Hanson

Downs

2017

PLoS ONE

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The Rid (YjgF/YER057c/UK114) protein family is a group of small, sequence diverse proteins that consists of eight subfamilies. The archetypal RidA subfamily is found in all domains, while the Rid1-7 subfamilies are present only in prokaryotes. Bacterial genomes often encode multiple members of the Rid superfamily. The best characterized member of this protein family, RidA from Salmonella enterica, is a deaminase that quenches the reactive metabolite 2-aminoacrylate generated by pyridoxal 5’-phosphate-dependent enzymes and ultimately spares certain enzymes from damage. The accumulation of 2-aminoacrylate can damage enzymes and lead to growth defects in bacteria, plants, and yeast. While all subfamily members have been annotated as imine deaminases based on the RidA characterization, experimental evidence to support this annotation exists for a single protein outside the RidA subfamily. Here we report that six proteins, spanning Rid subfamilies 1–3, deaminate a variety of imine/enamine substrates with differing specific activities. Proteins from the Rid2 and Rid3 subfamilies, but not from the RidA and Rid1 subfamilies deaminated iminoarginine, generated in situ by the Pseudomonas aeruginosa D-arginine dehydrogenase DauA. These data biochemically distinguished the subfamilies and showed Rid proteins have activity on a metabolite that is physiologically relevant in Pseudomonas and other bacteria.

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Section: Resultsmentioning

confidence: 99%

Members of the Rid protein family have broad imine deaminase activity and can accelerate the Pseudomonas aeruginosa D-arginine dehydrogenase (DauA) reaction in vitro

Hodge‐Hanson

Downs

2017

PLoS ONE

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“…RidA/YER057c/UK114 (Rid) family proteins (PF14588) are ubiquitous; phylogenetic analysis identified the archetypal RidA throughout all three domains of life, with additional subgroups (Rid1 to Rid7) present in prokaryotes ( 1 , 2 ). Biochemical genetic studies in the bacterium Salmonella enterica determined that RidA proteins are deaminases that hydrolyze the reactive enamine 2-aminoacrylate (2AA), and other enamine/imine substrates, to ketoacids ( 3 – 8 ). In cellular metabolism, 2AA is generated by pyridoxal 5′-phosphate (PLP)-dependent α,β-eliminase enzymes as an intermediate in the conversion of amino acids to pyruvate ( 3 , 4 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae

Ernst

Downs

2018

mBio

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A variety of metabolic deficiencies and human diseases arise from the disruption of mitochondrial enzymes and/or loss of mitochondrial DNA. Mounting evidence shows that eukaryotes have conserved enzymes that prevent the accumulation of reactive metabolites that cause stress inside the mitochondrion. 2-Aminoacrylate is a reactive enamine generated by pyridoxal 5′-phosphate-dependent α,β-eliminases as an obligatory intermediate in the breakdown of serine. In prokaryotes, members of the broadly conserved RidA family (PF14588) prevent metabolic stress by deaminating 2-aminoacrylate to pyruvate. Here, we demonstrate that unmanaged 2-aminoacrylate accumulation in Saccharomyces cerevisiae mitochondria causes transient metabolic stress and the irreversible loss of mitochondrial DNA. The RidA family protein Mmf1p deaminates 2-aminoacrylate, preempting metabolic stress and loss of the mitochondrial genome. Disruption of the mitochondrial pyridoxal 5′-phosphate-dependent serine dehydratases (Ilv1p and Cha1p) prevents 2-aminoacrylate formation, avoiding stress in the absence of Mmf1p. Furthermore, chelation of iron in the growth medium improves maintenance of the mitochondrial genome in yeast challenged with 2-aminoacrylate, suggesting that 2-aminoacrylate-dependent loss of mitochondrial DNA is influenced by disruption of iron homeostasis. Taken together, the data indicate that Mmf1p indirectly contributes to mitochondrial DNA maintenance by preventing 2-aminoacrylate stress derived from mitochondrial amino acid metabolism.

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“…RidA, reactive intermediate deaminase A, the archetypal protein of the family, has been primarily studied in Salmonella enterica for its role in quenching the reactive metabolite 2-aminoacrylate (2AA), a catalytic intermediate in a number of pyridoxal 5=-phosphate (PLP)-dependent reactions (Fig. 1) (3)(4)(5). RidA 2AA deaminase activity requires an active site arginine reside (Arg105 in S. enterica), and no other residues have been found to be essential for this activity (3).…”

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confidence: 99%

PA5339, a RidA Homolog, Is Required for Full Growth in Pseudomonas aeruginosa

2018

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The Rid protein superfamily (YjgF/YER057c/UK114) is found in all domains of life. The archetypal protein, RidA from , is a deaminase that quenches the reactive metabolite 2-aminoacrylate (2AA). 2AA deaminase activity is conserved in RidA proteins from humans, plants, yeast, archaea, and bacteria. Mutants of, , and that lack a functional RidA exhibit growth defects, suggesting that 2AA metabolic stress is similarly conserved. The PubSEED database shows (PAO1) encodes eight members of the Rid superfamily. Mutants of PAO1 lacking each of five Rid proteins were screened, and the mutant phenotypes that arose in the absence of PA5339 were dissected. A PA5339::Tn mutant has growth, motility, and biofilm defects that can all be linked to the accumulation of 2AA. Further, the PA5339 protein was demonstrably a 2AA deaminase and restored metabolic balance to a mutant The data presented here show that the RidA paradigm in had similarities to those described in other organisms but was distinct in that deleting only one of multiple homologs generated deficiencies. Based on the collective data presented here in, PA5339 was renamed RidA. RidA is a widely conserved protein that prevents endogenous metabolic stress caused by 2-aminoacrylate (2AA) damage to pyridoxal 5'-phosphate (PLP)-dependent enzymes in prokaryotes and eukaryotes. The framework for understanding the accumulation of 2AA and its consequences have largely been defined in We show here that in (PAO1), 2AA accumulation leads to reduced growth, compromised motility, and defective biofilm formation. This study expands our knowledge how the metabolic architecture of an organism contributes to the consequences of 2AA inactivation of PLP-dependent enzymes and identifies a key RidA protein in .

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L‐2,3‐diaminopropionate generates diverse metabolic stresses in Salmonella enterica

Cited by 23 publications

References 57 publications

Members of the Rid protein family have broad imine deaminase activity and can accelerate the Pseudomonas aeruginosa D-arginine dehydrogenase (DauA) reaction in vitro

Members of the Rid protein family have broad imine deaminase activity and can accelerate the Pseudomonas aeruginosa D-arginine dehydrogenase (DauA) reaction in vitro

Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae

PA5339, a RidA Homolog, Is Required for Full Growth in Pseudomonas aeruginosa

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