Redox modulation of glucose‐6‐P dehydrogenase in <i>Anacystis nidulans</i> and its ‘uncoupling’ by phage infection

Cséke, Csaba; Balogh, Árpád; Farkas, G. L.

doi:10.1016/0014-5793(81)81039-3

Cited by 31 publications

(9 citation statements)

References 17 publications

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“…These results suggested that, as has been proposed for the G6PDH from Anacystis nidulans (Cséke et al 1981), the activity of the long T. cruzi G6PDH may be regulated by the NADP/NADPH pair. We hypothesize that under normal conditions, the enzyme is maintained in its reduced lessactive form by NADPH, and under oxidative stress, in which the level of the reduced cofactor drops and other molecules like H 2 O 2 or dehydroascorbate are present, the enzyme is oxidized attaining its more active form.…”

Section: Glucose 6-phosphate Dehydrogenasesupporting

confidence: 69%

The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease

Igoillo-Esteve

Maugeri

Stern

et al. 2007

An. Acad. Bras. Ciênc.

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Trypanosoma cruzi is highly sensitive to oxidative stress caused by reactive oxygen species. Trypanothione, the parasite's major protection against oxidative stress, is kept reduced by trypanothione reductase, using NADPH; the major source of the reduced coenzyme seems to be the pentose phosphate pathway. Its seven enzymes are present in the four major stages in the parasite's biological cycle; we have cloned and expressed them in Escherichia coli as active proteins. Glucose 6-phosphate dehydrogenase, which controls glucose flux through the pathway by its response to the NADP/NADPH ratio, is encoded by a number of genes per haploid genome, and is induced up to 46-fold by hydrogen peroxide in metacyclic trypomastigotes. The genes encoding 6-phosphogluconolactonase, 6-phosphogluconate dehydrogenase, transaldolase and transketolase are present in the CL Brener clone as a single copy per haploid genome. 6-phosphogluconate dehydrogenase is very unstable, but was stabilized introducing two salt bridges by site-directed mutagenesis. Ribose-5-phosphate isomerase belongs to Type B; genes encoding Type A enzymes, present in mammals, are absent. Ribulose-5-phosphate epimerase is encoded by two genes. The enzymes of the pathway have a major cytosolic component, although several of them have a secondary glycosomal localization, and also minor localizations in other organelles.

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Section: Glucose 6-phosphate Dehydrogenasesupporting

confidence: 69%

The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease

Igoillo-Esteve

Maugeri

Stern

et al. 2007

An. Acad. Bras. Ciênc.

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“…This thioredoxin reductase is apparently identical to a previously described modulator protein called ferralterin [151]. In contrast to these results, two other groups have reported NADPHdependent thioredoxin reductase activity in partially purified extracts of Anacystis nidulans after phage infection [152] and Anabaena 7119 [66]. Whether one or both reductase systems function in cyanobacteria and under what conditions is not known.…”

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confidence: 58%

Thioredoxin and related proteins in procaryotes

Gleason

Holmgren

1988

FEMS Microbiology Letters

161

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Thioredoxin is a small (Mr 12,000) ubiquitous redox protein with the conserved active site structure: ‐Trp‐Cys‐Gly‐Pro‐Cys‐. The oxidized form (Trx‐S2) contains a disulfide bridge which is reduced by NADPH and thioredoxin reductase; the reduced form [Trx(SH)2] is a powerful protein disulfide oxidoreductase. Thioredoxins have been characterized in a wide variety of prokaryotic cells, and generally show about 50% amino acid homology to Escherichia coli thioredoxin with a known three‐dimensional structure. In vitro Trx‐(SH)2 serves as a hydrogen donor for ribonucleotide reductase, an essential enzyme in DNA synthesis, and for enzymes reducing sulfate or methionine sulfoxide. E. coli Trx‐(SH)2 is essential for phage T7 DNA replication as a subunit of T7 DNA polymerase and also for assembly of the filamentous phages f1 and M13 perhaps through its localization at the cellular plasma membrane. Some photosynthetic organisms reduce Trx‐S2 by light and ferrodoxin; Trx‐(SH)2 is used as a disulfide reductase to regulate the activity of enzymes by thiol redox control. Thioredoxin‐negative mutants (trxA) of E. coli are viable making the precise cellular physiological functions of thioredoxin unknown. Another small E. coli protein, glutaredoxin, enables GSH to be hydrogen donor for ribonucleotide reductase or PAPS reductase. Further experiments with molecular genetic techniques are required to define the relative roles of the thioredoxin and glutaredoxin systems in intracellular redox reactions.

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“…These observations suggest that among the trypanosomatid G6PDHs studied, only the activity of the T. cruzi enzyme is regulated by the redox state of the cell, in a similar way as reported for the enzyme from chloroplasts and cyanobacteria. Indeed, kinetic studies with the two purified recombinant forms showed that the long form was 4-fold more sensitive for inhibition by the product NAPDH than the short one, suggesting that its activity is regulated by the NADP + /NADPH ratio in the cell compartment where the enzyme is located, similarly as has been proposed for the enzyme from Anacystis nidulans [48]. …”

Section: Glucose-6-phosphate Dehydrogenase In Trypanosomatidsmentioning

confidence: 75%

Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery

Gupta

Igoillo-Esteve

Michels

et al. 2011

Molecular Biology International

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In trypanosomatids, glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentosephosphate pathway, is essential for the defense of the parasite against oxidative stress. Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana G6PDHs have been characterized. The parasites' G6PDHs contain a unique 37 amino acid long N-terminal extension that in T. cruzi seems to regulate the enzyme activity in a redox-state-dependent manner. T. brucei and T. cruzi G6PDHs, but not their Leishmania spp. counterpart, are inhibited, in an uncompetitive way, by steroids such as dehydroepiandrosterone and derivatives. The Trypanosoma enzymes are more susceptible to inhibition by these compounds than the human G6PDH. The steroids also effectively kill cultured trypanosomes but not Leishmania and are presently considered as promising leads for the development of new parasite-selective chemotherapeutic agents.

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Redox modulation of glucose‐6‐P dehydrogenase in Anacystis nidulans and its ‘uncoupling’ by phage infection

Cited by 31 publications

References 17 publications

The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease

The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease

Thioredoxin and related proteins in procaryotes

Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery

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