Journalartikel

Jahr der Veröffentlichung: 2002

Seiten: 2779-2784

Zeitschrift: Journal of Biological Chemistry

Bandnummer: 277

Heftnummer: 4

ISSN: 0021-9258

eISSN: 1083-351X

Open Access Status: Hybrid

DOI Link: https://doi.org/10.1074/jbc.M108190200

Verlag: Elsevier

Abstract: 
As part of our studies on the nitric oxide-related pathology of cerebral malaria, we show that the antioxidative enzyme glutathione reductase (GR) is inactivated by peroxynitrite, with GR from the malarial parasite Plasmodium falciparum being more sensitive than human GR. The crystal structure of modified human GR at 1.9-Angstrom resolution provides the first picture of protein inactivation by peroxynitrite and reveals that this is due to the exclusive nitration of 2 Tyr residues (residues 106 and 114) at the glutathione disulfide-binding site. The selective nitration explains the impairment of binding the peptide substrate and thus the nearly 1000-fold decrease in catalytic efficiency (k(cat)/K-m) of glutathione reductase observed at physiologic pH. By oxidizing the catalytic dithiol to a disulfide, peroxynitrite itself can act as a substrate of unmodified and bisnitrated P. falciparum glutathione reductase.

Harvard-Zitierstil: Savvides, S., Scheiwein, M., Böhme, C., Arteel, G., Karplus, P., Becker, K., et al. (2002) Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite, Journal of Biological Chemistry, 277(4), pp. 2779-2784. https://doi.org/10.1074/jbc.M108190200

APA-Zitierstil: Savvides, S., Scheiwein, M., Böhme, C., Arteel, G., Karplus, P., Becker, K., & Schirmer, R. (2002). Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite. Journal of Biological Chemistry. 277(4), 2779-2784. https://doi.org/10.1074/jbc.M108190200