Genetic Suppressors and Recovery of Repressed Biochemical Memory

Beckwith, Jon

doi:10.1074/jbc.x800017200

“…For instance, lipoylated E2 from Mycobacterium tuberculosis reduces a thioredoxinlike protein (AhpD), thereby indirectly supporting the peroxidase activity of a peroxiredoxin (AhpC) (26). Besides, it was also proposed that the reduced form of lipoylated enzymes could donate electrons to ribonucleotide reductase via Grx1 (40). Interestingly, the redox state of the complex-bound lipoate is an indicator of the availability of the reaction substrates (2-oxo acid, CoA, and NAD ϩ ) and thiol-disulfide status of the medium (19).…”

Section: Discussionmentioning

confidence: 99%

Ohr (Organic Hydroperoxide Resistance Protein) Possesses a Previously Undescribed Activity, Lipoyl-dependent Peroxidase

Cussiol

¹

,

Alegria

²

,

Szweda

³

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

The Ohr (organic hydroperoxide resistance) family of 15-kDa Cys-based, thiol-dependent peroxidases is central to the bacterial response to stress induced by organic hydroperoxides but not by hydrogen peroxide. Ohr has a unique three-dimensional structure and requires dithiols, but not monothiols, to support its activity. However, the physiological reducing system of Ohr has not yet been identified. Here we show that lipoylated enzymes present in the bacterial extracts of Xylella fastidiosa interacted physically and functionally with this Cys-based peroxidase, whereas thioredoxin and glutathione systems failed to support Ohr peroxidase activity. Furthermore, we could reconstitute in vitro three lipoyl-dependent systems as the Ohr physiological reducing systems. We also showed that OsmC from Escherichia coli, an orthologue of Ohr from Xylella fastidiosa, is specifically reduced by lipoyl-dependent systems. These results represent the first description of a Cys-based peroxidase that is directly reduced by lipoylated enzymes.

show abstract

“…Furthermore, lipoylated E2 from Mycobacterium tuberculosis reduces a thioredoxin-like protein (AhpD), thereby indirectly supporting the peroxidase activity of AhpC [207]. Besides, lipoylated enzymes can donate electrons to ribonucleotide reductase via Grx1 [208]. The factors responsible for the specificity of lipoylated proteins towards their targets are still poorly understood.…”

Section: Other Thiol-disulfide Oxidoreductasesmentioning

confidence: 99%

Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions

Netto

¹

,

Oliveira

²

,

Tairum

³

et al. 2016

Free Radical Research

View full text Add to dashboard Cite

Thiol-disulfide exchange reactions are highly reversible, displaying nucleophilic substitutions mechanism (S(N)2 type). For aliphatic, low molecular thiols, these reactions are slow, but can attain million times faster rates in enzymatic processes. Thioredoxin (Trx) proteins were the first enzymes described to accelerate thiol-disulfide exchange reactions and their high reactivity is related to the high nucleophilicity of the attacking thiol. Substrate specificity in Trx is achieved by several factors, including polar, hydrophobic, and topological interactions through a groove in the active site. Glutaredoxin (Grx) enzymes also contain the Trx fold, but they do not share amino acid sequence similarity with Trx. A conserved glutathione binding site is a typical feature of Grx that can reduce substrates by two mechanisms (mono and dithiol). The high reactivity of Grx enzymes is related to the very acid pK(a) values of reactive Cys that plays roles as good leaving groups. Therefore, although distinct oxidoreductases catalyze similar thiol–disulfide exchange reactions, their enzymatic mechanisms vary. PDI and DsbA are two other oxidoreductases, but they are involved in disulfide bond formation, instead of disulfide reduction, which is related to the oxidative environment where they are found. PDI enzymes and DsbC are endowed with disulfide isomerase activity, which is related with their tetra-domain architecture. As illustrative description of specificity in thiol-disulfide exchange, redox aspects of transcription activation in bacteria, yeast, and mammals are presented in an evolutionary perspective. Therefore, thiol-disulfide exchange reactions play important roles in conferring specificity to pathways, a required feature for signaling.

show abstract

“…For instance, lipoylated E2 from Mycobacterium tuberculosis reduces a thioredoxinlike protein (AhpD), thereby indirectly supporting the peroxidase activity of a peroxiredoxin (AhpC) (26). Besides, it was also proposed that the reduced form of lipoylated enzymes could donate electrons to ribonucleotide reductase via Grx1 (40). Interestingly, the redox state of the complex-bound lipoate is an indicator of the availability of the reaction substrates (2-oxo acid, CoA, and NAD ϩ ) and thiol-disulfide status of the medium (19).…”

Section: Discussionmentioning

confidence: 99%

Ohr (Organic hydroperoxide resistance protein) Possesses a Previously Undescribed Activity: Lipoyldependent Peroxidase

Cussiol

¹

,

Alegria

²

,

Szweda

³

et al. 2010

Free Radical Biology and Medicine

View full text Add to dashboard Cite

The Ohr (organic hydroperoxide resistance) family of 15-kDa Cys-based, thiol-dependent peroxidases is central to the bacterial response to stress induced by organic hydroperoxides but not by hydrogen peroxide. Ohr has a unique three-dimensional structure and requires dithiols, but not monothiols, to support its activity. However, the physiological reducing system of Ohr has not yet been identified. Here we show that lipoylated enzymes present in the bacterial extracts of Xylella fastidiosa interacted physically and functionally with this Cys-based peroxidase, whereas thioredoxin and glutathione systems failed to support Ohr peroxidase activity. Furthermore, we could reconstitute in vitro three lipoyl-dependent systems as the Ohr physiological reducing systems. We also showed that OsmC from Escherichia coli, an orthologue of Ohr from Xylella fastidiosa, is specifically reduced by lipoyl-dependent systems. These results represent the first description of a Cys-based peroxidase that is directly reduced by lipoylated enzymes.

show abstract

Genetic Suppressors and Recovery of Repressed Biochemical Memory

Cited by 10 publications

References 51 publications

Ohr (Organic Hydroperoxide Resistance Protein) Possesses a Previously Undescribed Activity, Lipoyl-dependent Peroxidase

Ohr (Organic Hydroperoxide Resistance Protein) Possesses a Previously Undescribed Activity, Lipoyl-dependent Peroxidase

Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions

Ohr (Organic hydroperoxide resistance protein) Possesses a Previously Undescribed Activity: Lipoyldependent Peroxidase

Contact Info

Product

Resources

About