Functional characterization of methionine sulfoxide reductase A from Trypanosoma spp.

Arias, Diego Gustavo; Cabeza, Matías Sebastián; Erben, Esteban; Carranza, Pedro Gabriel; Luján, Hugo D.; Iñón, Maria T. Téllez de; Iglesias, Alberto A.; Guerrero, Sandra

doi:10.1016/j.freeradbiomed.2010.10.695

Cited by 31 publications

(47 citation statements)

References 48 publications

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“…T. brucei Tpx plays a central role in most of the T(SH 2 )-dependent parasite pathways (1). Examples are the detoxification of hydroperoxides and, as shown recently, the reduction of protein-bound methionine sulfoxide residues (13). Most importantly, the T(SH) 2 /Tpx system delivers the reducing equivalents for the synthesis of DNA precursors catalyzed by ribonucleotide reductase and thus is involved in parasite replication (14).…”

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confidence: 99%

High Throughput Screening against the Peroxidase Cascade of African Trypanosomes Identifies Antiparasitic Compounds That Inactivate Tryparedoxin

Fueller

Jehle

Putzker

et al. 2012

Journal of Biological Chemistry

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Background: Hydroperoxide detoxification in African trypanosomes relies on a cascade composed of trypanothione, trypanothione reductase, tryparedoxin, and tryparedoxin peroxidases. Results: A library screening against the peroxidase system unraveled trypanocidal compounds that inactivate tryparedoxin in vitro and in the intact parasite. Conclusion: Tryparedoxin is a druggable target. Significance: Detection of novel target molecules is a crucial step to overcome the unsatisfactory chemotherapy of sleeping sickness.

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High Throughput Screening against the Peroxidase Cascade of African Trypanosomes Identifies Antiparasitic Compounds That Inactivate Tryparedoxin

Fueller

Jehle

Putzker

et al. 2012

Journal of Biological Chemistry

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“…The main low molecular mass thiol is trypanothione [T(SH) 2 ]. It is synthesized from two molecules of glutathione (GSH, light gray background) and one spermidine (Sp, dark gray background) with mono(glutathionyl)spermidine (Gsp; gray backgrounds) as intermediate.…”

Section: Fig 1 the Trypanothione-based Redox Metabolism Of Trypanosmentioning

confidence: 99%

“…For instance, the parasite thiol redox homeostasis is maintained by the unique trypanothione/trypanothione reductase couple, which substitutes for the glutathione/ glutathione reductase and the thioredoxin/thioredoxin reductase systems of the host (24,39,44,45). Trypanothione [T(SH) 2 ; Fig. 1A] is synthesized from glutathione and spermidine with monoglutathionylspermidine (Gsp) as intermediate (44).…”

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“…The dithiol T(SH) 2 constitutes the main low molecular mass thiol of trypanosomatids and acts as redox cofactor in a plethora of cellular functions (39,44,45). The transfer of reducing equivalents from T(SH) 2 to protein targets can be mediated by thioredoxin-(Trx), tryparedoxin-(TXN) and glutaredoxin-type oxidoreductases (12,20,63,77; Fig. 1B).…”

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“…The parasite glutaredoxins (Grxs) probably have rather specialized functions and are the subject of this review. T(SH) 2 has also been shown to complex to electrophiles such as heavy metals and drugs or to ligate endobiotics (i.e., methylglyoxal) or nitro-iron complexes (7, for recent reviews see 44,45). On the other hand, iron is an essential element that trypanosomatids take up from the extracellular milieu by mechanisms that differ between species (reviewed in 55,83).…”

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Mono- and Dithiol Glutaredoxins in the Trypanothione-Based Redox Metabolism of Pathogenic Trypanosomes

Comini

Krauth‐Siegel²,

Bellanda³

2013

Antioxidants & Redox Signaling

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Significance: Glutaredoxins are ubiquitous small thiol proteins of the thioredoxin-fold superfamily. Two major groups are distinguished based on their active sites: the dithiol (2-C-Grxs) and the monothiol (1-C-Grxs) glutaredoxins with a CXXC and a CXXS active site motif, respectively. Glutaredoxins are involved in cellular redox and/or iron sulfur metabolism. Usually their functions are closely linked to the glutathione system. Trypanosomatids, the causative agents of several tropical diseases, rely on trypanothione as principal low molecular mass thiol, and their glutaredoxins readily react with the unique bis(glutathionyl) spermidine conjugate.

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Trypanothione‐Based Redox Metabolism of Trypanosomatids

Comini

Flohé

2013

Trypanosomatid Diseases

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Functional characterization of methionine sulfoxide reductase A from Trypanosoma spp.

Cited by 31 publications

References 48 publications

High Throughput Screening against the Peroxidase Cascade of African Trypanosomes Identifies Antiparasitic Compounds That Inactivate Tryparedoxin

High Throughput Screening against the Peroxidase Cascade of African Trypanosomes Identifies Antiparasitic Compounds That Inactivate Tryparedoxin

Mono- and Dithiol Glutaredoxins in the Trypanothione-Based Redox Metabolism of Pathogenic Trypanosomes

Trypanothione‐Based Redox Metabolism of Trypanosomatids

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