Journalartikel

Jahr der Veröffentlichung: 2000

Seiten: 40180-40186

Zeitschrift: Journal of Biological Chemistry

Bandnummer: 275

Heftnummer: 51

ISSN: 0021-9258

eISSN: 1083-351X

DOI Link: https://doi.org/10.1074/jbc.M007633200

Verlag: Elsevier

Abstract: 
In most living cells, redox homeostasis is based both on the glutathione and the thioredoxin system. In the malaria parasite Plasmodium falciparum antioxidative proteins represent promising targets for the development of antiparasitic drugs. We cloned and expressed a thioredoxin of P. falciparum (pftrx), and we improved the stable expression of the thioredoxin reductase (PfTrxR) of the parasite by multiple silent mutagenesis. Both proteins were biochemically characterized and compared with the human host thioredoxin system. Intriguingly, the 13-kDa protein PfTrx is a better substrate for human TrxR (K-m = 2 muM, K-cat = 3300 min(-1)) than for P. falciparum TrxR (K-m = 10.4 muM, k(cat) = 3100 min(-1)). Possessing a midpoint potential of -270 mV, PfTrx was found to reduce the disease-related metabolites S-nitrosoglutathione and GSSG;. The rate constant Fz, for the reaction between reduced P. falciparum thioredoxin and GSSG was determined to be 0.039 muM(-1) min(-1) at 25 degreesC and pH 7.4. The k(2) for thioredoxins from man, Drosophila melanogaster, and Escherichia coli was similar to5 times lower. Our data suggest that GSSG reduction can be supported at a high rate by the TrxR/Trx system in glutathione reductase-deficient cells; this may be relevant for certain stages of the malarial parasite but also for cells containing high [GSSG] of other organisms like dormant forms of Neurospora, glutathione reductase-deficient yeast mutants, or CD4(+) lymphocytes of AIDS patients.

Harvard-Zitierstil: Kanzok, S., Schirmer, R., Türbachova, I., Iozef, R. and Becker, K. (2000) The thioredoxin system of the malaria parasite Plasmodium falciparum - Glutathione reduction revisited, Journal of Biological Chemistry, 275(51), pp. 40180-40186. https://doi.org/10.1074/jbc.M007633200

APA-Zitierstil: Kanzok, S., Schirmer, R., Türbachova, I., Iozef, R., & Becker, K. (2000). The thioredoxin system of the malaria parasite Plasmodium falciparum - Glutathione reduction revisited. Journal of Biological Chemistry. 275(51), 40180-40186. https://doi.org/10.1074/jbc.M007633200