A Reexamination of Thioredoxin Reductase from <i>Thermoplasma acidophilum</i>, a Thermoacidophilic Euryarchaeon, Identifies It as an NADH-Dependent Enzyme

Susanti, Dwi; Loganathan, Usha; Compton, Austin; Mukhopadhyay, Biswarup

doi:10.1021/acsomega.7b00640

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…Generation of recombinant proteins. The method for generation of recombinant proteins has been described previously (55,56). In short, the DNA for the coding region of M. tuberculosis fbiB (rv3262) was PCR amplified and cloned into the NdeI and BamHI sites of pTEV5 (55), generating the expression vector pUL3262; pTEV5 allows the expression of a cloned gene under the control of a lacO/LacI-controlled T7 promoter, producing a protein linked to an NH 2 -terminal His 6 -tag via a tobacco etch virus (TEV) protease cleavage site (55,57).…”

Section: Methodsmentioning

confidence: 99%

Coenzyme F ₄₂₀ -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F ₄₂₀ in Mycobacteria

2018

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Coenzyme F420 plays a key role in the redox metabolisms of various archaea and bacteria, including Mycobacterium tuberculosis. In M. tuberculosis, F420-dependent reactions have been linked to several virulence factors. F420 carries multiple glutamate residues in the side chain, forming F420-n species (n, number of glutamate residues), and the length of this side chain impacts cellular physiology. M. tuberculosis strains with F420 species carrying shorter side chains exhibit resistance to delamanid and pretomanid, two new tuberculosis (TB) drugs. Thus, the process of polyglutamylation of F420 is of great interest. It has been known from genetic analysis that in mycobacteria an F420-0 γ-glutamyl ligase (FbiB) introduces up to seven glutamate residues into F420. However, purified FbiB of M. tuberculosis (MtbFbiB) is either inefficient or incapable of incorporating more than two glutamates. We found that, in vitro, MtbFbiB synthesized side chains containing up to seven glutamate residues if F420 was presented to the enzyme in a two-electron reduced state (F420H2). Our genetic analysis in Mycobacterium bovis BCG and Mycobacterium smegmatis and an analysis of literature data on M. tuberculosis revealed that in these mycobacteria the polyglutamylation process requires the assistance of F420-dependent glucose-6-phosphate dehydrogenase (Fgd) which reduces F420 to F420H2. We hypothesize that, starting with F420-0H2, the amino-terminal domain of FbiB builds F420-2H2, which is then transferred to the carboxy-terminal domain for further glutamylation; F420-2H2 modifies the carboxy-terminal domain structurally to accommodate longer glutamyl chains. This system is analogous to folylpolyglutamate synthase, which introduces more than one glutamate residue into folate only after this vitamin is reduced to tetrahydrofolate. IMPORTANCE Coenzyme F420-dependent reactions of Mycobacterium tuberculosis, which causes tuberculosis, potentially contributes to the virulence of this bacterium. The coenzyme carries a glutamic acid-derived tail, the length of which influences the metabolism of M. tuberculosis. Mutations that eliminate the production of F420 with longer tails make M. tuberculosis resistant to two new tuberculosis drugs. This report describes that the synthesis of longer glutamyl tails of F420 requires concerted actions of two enzymes, one of which reduces the coenzyme prior to the action of the other, which catalyzes polyglutamylation. This knowledge will help to develop more effective tuberculosis (TB) drugs. Remarkably, the introduction of multiple glutamate residues into the sidechain of folate (vitamin B9) requires similar concerted actions, where one enzyme reduces the vitamin to tetrahydrofolate and the other catalyzes polyglutamylation; folate is required for DNA and amino acid synthesis. Thus, the reported research has also revealed a key similarity between two important cellular systems.

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Section: Methodsmentioning

confidence: 99%

Coenzyme F ₄₂₀ -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F ₄₂₀ in Mycobacteria

2018

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“…Archaeal protein disulfide relay systems may provide the reductant for MetO reduction by MSR enzymes that use a Cys A nucleophile. Archaeal NAD(P)H-dependent protein disulfide oxidoreductase relay systems which could serve this role include: (i) Trx or Grx/TrxR [ 66 , 67 ], (ii) protein disulfide oxidoreductase (PDO)/TrxR [ 68 ], (iii) methanoredoxin (Mrx)/coenzyme M disulfide reductase (CoMR) [ 69 , 70 ] and (iv) bis-γ-glutamylcystine reductase (BggR) [ 71 , 72 ] ( Figure 5 ). An archaeal F420-dependent TrxR is also described [ 73 ].…”

Section: Protein Disulfide Relay Systems Of Archaeamentioning

confidence: 99%

Methionine Sulfoxide Reductases of Archaea

Maupin-Furlow

2018

Antioxidants

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Methionine sulfoxide reductases are found in all domains of life and are important in reversing the oxidative damage of the free and protein forms of methionine, a sulfur containing amino acid particularly sensitive to reactive oxygen species (ROS). Archaea are microbes of a domain of life distinct from bacteria and eukaryotes. Archaea are well known for their ability to withstand harsh environmental conditions that range from habitats of high ROS, such as hypersaline lakes of intense ultraviolet (UV) radiation and desiccation, to hydrothermal vents of low concentrations of dissolved oxygen at high temperature. Recent evidence reveals the methionine sulfoxide reductases of archaea function not only in the reduction of methionine sulfoxide but also in the ubiquitin-like modification of protein targets during oxidative stress, an association that appears evolutionarily conserved in eukaryotes. Here is reviewed methionine sulfoxide reductases and their distribution and function in archaea.

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“…archaeon Methanocaldococcus jannaschii, mediates electron transfer from coenzyme F 420 (8-hydroxy-5-deazaflavin) to the disulfide bridge in Trx (11).…”

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confidence: 99%

Direct Electron Transfer between the frhAGB -Encoded Hydrogenase and Thioredoxin Reductase in the Nonmethanogenic Archaeon Thermococcus onnurineus NA1

Jung

Lim

Yang

et al. 2020

Appl Environ Microbiol

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To date, NAD(P)H, ferredoxin, and coenzyme F420 have been identified as electron donors for thioredoxin reductase (TrxR). In this study, we present a novel electron source for TrxR. In the hyperthermophilic archaeon Thermococcus onnurineus NA1, the frhAGB-encoded hydrogenase, a homolog of the F420-reducing hydrogenase of methanogens, was demonstrated to interact with TrxR in coimmunoprecipitation experiments and in vitro pulldown assays. Electrons derived from H2 oxidation by the frhAGB-encoded hydrogenase were transferred to TrxR and reduced Pdo, a redox partner of TrxR. Interaction and electron transfer were observed between TrxR and the heterodimeric hydrogenase complex (FrhAG) as well as the heterotrimeric complex (FrhAGB). Hydrogen-dependent reduction of TrxR was 7-fold less efficient than when NADPH was the electron donor. This study not only presents a different type of electron donor for TrxR but also reveals new functionality of the frhAGB-encoded hydrogenase utilizing a protein as an electron acceptor. IMPORTANCE This study has importance in that TrxR can use H2 as an electron donor with the aid of the frhAGB-encoded hydrogenase as well as NAD(P)H in T. onnurineus NA1. Further studies are needed to explore the physiological significance of this protein. This study also has importance as a significant step toward understanding the functionality of the frhAGB-encoded hydrogenase in a nonmethanogen; the hydrogenase can transfer electrons derived from oxidation of H2 to a protein target by direct contact without the involvement of an electron carrier, which is distinct from the mechanism of its homologs, F420-reducing hydrogenases of methanogens.

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A Reexamination of Thioredoxin Reductase from Thermoplasma acidophilum, a Thermoacidophilic Euryarchaeon, Identifies It as an NADH-Dependent Enzyme

Cited by 10 publications

References 34 publications

Coenzyme F ₄₂₀ -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F ₄₂₀ in Mycobacteria

Coenzyme F ₄₂₀ -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F ₄₂₀ in Mycobacteria

Methionine Sulfoxide Reductases of Archaea

Direct Electron Transfer between the frhAGB -Encoded Hydrogenase and Thioredoxin Reductase in the Nonmethanogenic Archaeon Thermococcus onnurineus NA1

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A Reexamination of Thioredoxin Reductase from Thermoplasma acidophilum, a Thermoacidophilic Euryarchaeon, Identifies It as an NADH-Dependent Enzyme

Cited by 10 publications

References 34 publications

Coenzyme F 420 -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F 420 in Mycobacteria

Coenzyme F 420 -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F 420 in Mycobacteria

Methionine Sulfoxide Reductases of Archaea

Direct Electron Transfer between the frhAGB -Encoded Hydrogenase and Thioredoxin Reductase in the Nonmethanogenic Archaeon Thermococcus onnurineus NA1

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Coenzyme F ₄₂₀ -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F ₄₂₀ in Mycobacteria

Coenzyme F ₄₂₀ -Dependent Glucose-6-Phosphate Dehydrogenase-Coupled Polyglutamylation of Coenzyme F ₄₂₀ in Mycobacteria