Journal article

Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite


Authors listSavvides, SN; Scheiwein, M; Böhme, CC; Arteel, GE; Karplus, PA; Becker, K; Schirmer, RH

Publication year2002

Pages2779-2784

JournalJournal of Biological Chemistry

Volume number277

Issue number4

ISSN0021-9258

eISSN1083-351X

Open access statusHybrid

DOI Linkhttps://doi.org/10.1074/jbc.M108190200

PublisherElsevier


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.



Citation Styles

Harvard Citation styleSavvides, 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 Citation styleSavvides, 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


Last updated on 2025-10-06 at 09:25