1k4q
From Proteopedia
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Human Glutathione Reductase Inactivated by Peroxynitrite
Contents |
Overview
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.
Disease
Known disease associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[138300]
About this Structure
1K4Q is a Single protein structure of sequence from Homo sapiens with FAD as ligand. Active as Glutathione-disulfide reductase, with EC number 1.8.1.7 Full crystallographic information is available from OCA.
Reference
Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite., Savvides SN, Scheiwein M, Bohme CC, Arteel GE, Karplus PA, Becker K, Schirmer RH, J Biol Chem. 2002 Jan 25;277(4):2779-84. Epub 2001 Nov 8. PMID:11705998
Page seeded by OCA on Mon Nov 12 17:47:12 2007
