http://www.cnr.it/ontology/cnr/individuo/prodotto/ID55865

The mycobacterial thioredoxin peroxidase can act as a one-cysteine-peroxiredoxin (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

The mycobacterial thioredoxin peroxidase can act as a one-cysteine-peroxiredoxin (Articolo in rivista) (literal)

Anno

2006-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1074/jbc.M601008200 (literal)

Alternative label

Madia Trujillo, PierLuigi Mauri, Louise Benazzi, Marcelo Comini, Antonella De Palma, Leopold Flohé, Rafael Radi, Matthias Stehr, Mahavir Singh, Fulvio Ursini, Timo Jaeger (2006)
The mycobacterial thioredoxin peroxidase can act as a one-cysteine-peroxiredoxin
in The Journal of biological chemistry (Print)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Madia Trujillo, PierLuigi Mauri, Louise Benazzi, Marcelo Comini, Antonella De Palma, Leopold Flohé, Rafael Radi, Matthias Stehr, Mahavir Singh, Fulvio Ursini, Timo Jaeger (literal)

Pagina inizio

20555 (literal)

Pagina fine

20566 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

281 (literal)

Rivista

?The ?Journal of biological chemistry (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

29 (literal)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

ITB-CNR Università di Padova Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Avda. General Flores 2125, UY-11800 Montevideo, Uruguay, Centre of Biochemistry, University of Heidelberg, Im Neuenheimer Feld 504, D-69120 Heidelberg, Germany Department of Genome Analysis, German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany (literal)

Titolo

The mycobacterial thioredoxin peroxidase can act as a one-cysteine-peroxiredoxin (literal)

Abstract

Thioredoxin peroxidase (TPx) has been reported to dominate the defense against H2O2, other hydroperoxides, and peroxynitrite at the expense of thioredoxin (Trx) B and C in Mycobacterium tuberculosis (Mt). By homology, the enzyme has been classified as an atypical 2-C-peroxiredoxin (Prx), with Cys(60) as the \"peroxidatic\" cysteine (C-P) forming a complex catalytic center with Cys(93) as the \"resolving\" cysteine (CR). Site-directed mutagenesis confirms Cys(60) to be CP and Cys(80) to be catalytically irrelevant. Replacing Cys(93) with serine leads to fast inactivation as seen by conventional activity determination, which is associated with oxidation of Cys(60) to a sulfinic acid derivative. However, in comparative stopped-flow analysis, WT-MtTPx and MtTPx C93S reduce peroxynitrite and react with TrxB and -C similarly fast. Reduction of pre-oxidized WT-MtTPx and MtTPx C93S by MtTrxB is demonstrated by monitoring the redox-dependent tryptophan fluorescence of MtTrxB. Furthermore, MtTPx C93S remains stable for 10 min at a morpholinosydnonimine hydrochloride-generated low flux of peroxynitrite and excess MtTrxB in a dihydrorhodamine oxidation model. Liquid chromatography-tandem mass spectrometry analysis revealed disulfide bridges between Cys(60) and Cys(93) and between Cys(60) and Cys(80) in oxidized WT-MtTPx. Reaction of pre-oxidized WT-MtTPx and MtTPx (CS)-S-93 with MtTrxB C34S or MtTrxC C40S yielded dead-end intermediates in which the Trx mutants are preferentially linked via disulfide bonds to Cys(60) and never to Cys(93) of the TPx. It is concluded that neither Cys(80) nor Cys(93) is required for the catalytic cycle of the peroxidase. Instead, MtTPx can react as a 1-C-Prx with Cys(60) being the site of attack for both the oxidizing and the reducing substrate. The role of Cys(93) is likely to conserve the oxidation equivalents of the sulfenic acid state of CP as a disulfide bond to prevent overoxidation of Cys(60) under a restricted supply of reducing substrate. (literal)

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