1k4q
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | As part of our studies on the nitric oxide-related pathology of cerebral | + | 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== | ==Disease== | ||
| Line 17: | Line 17: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Arteel, G | + | [[Category: Arteel, G E.]] |
[[Category: Becker, K.]] | [[Category: Becker, K.]] | ||
| - | [[Category: Boehme, C | + | [[Category: Boehme, C C.]] |
| - | [[Category: Karplus, P | + | [[Category: Karplus, P A.]] |
| - | [[Category: Savvides, S | + | [[Category: Savvides, S N.]] |
[[Category: Scheiwein, M.]] | [[Category: Scheiwein, M.]] | ||
| - | [[Category: Schirmer, R | + | [[Category: Schirmer, R H.]] |
[[Category: FAD]] | [[Category: FAD]] | ||
[[Category: flavoenzyme]] | [[Category: flavoenzyme]] | ||
[[Category: nitrotyrosine]] | [[Category: nitrotyrosine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:30:09 2008'' |
Revision as of 11:30, 21 February 2008
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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 diseases associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[138300], Mental retardation, autosomal recessive, 6 OMIM:[138244]
About this Structure
1K4Q is a Single protein structure of sequence from Homo sapiens with 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
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