1K4Q

Human Glutathione Reductase Inactivated by Peroxynitrite

Summary for 1K4Q

• Entry DOI: 10.2210/pdb1k4q/pdb
• Descriptor: Glutathione Reductase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: nitrotyrosine, flavoenzyme, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Mitochondrial: Mitochondrion. Isoform Cytoplasmic: Cytoplasm: P00390
• Total number of polymer chains: 1
• Total formula weight: 50853.97

Authors

Savvides, S.N.,Scheiwein, M.,Boehme, C.C.,Arteel, G.E.,Karplus, P.A.,Becker, K.,Schirmer, R.H. (deposition date: 2001-10-08, release date: 2002-01-30, Last modification date: 2025-03-26)

Primary citation

Savvides, S.N.,Scheiwein, M.,Bohme, C.C.,Arteel, G.E.,Karplus, P.A.,Becker, K.,Schirmer, R.H.
Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite.
J.Biol.Chem., 277:2779-2784, 2002

PubMed 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-A 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.

PubMed: 11705998
DOI: 10.1074/jbc.M108190200

Experimental method

X-RAY DIFFRACTION (1.9 Å)