1K4Q

Human Glutathione Reductase Inactivated by Peroxynitrite

1K4Q の概要

• エントリーDOI: 10.2210/pdb1k4q/pdb
• 分子名称: Glutathione Reductase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: nitrotyrosine, flavoenzyme, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform Mitochondrial: Mitochondrion. Isoform Cytoplasmic: Cytoplasm: P00390
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50853.97

構造登録者

Savvides, S.N.,Scheiwein, M.,Boehme, C.C.,Arteel, G.E.,Karplus, P.A.,Becker, K.,Schirmer, R.H. (登録日: 2001-10-08, 公開日: 2002-01-30, 最終更新日: 2025-03-26)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.9 Å)