1GRH

INHIBITION OF HUMAN GLUTATHIONE REDUCTASE BY THE NITROSOUREA DRUGS 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA AND 1-(2-CHLOROETHYL)-3-(2-HYDROXYETHYL)-1-NITROSOUREA

1GRH の概要

• エントリーDOI: 10.2210/pdb1grh/pdb
• 関連するPDBエントリー: 1GRG
• 分子名称: GLUTATHIONE REDUCTASE, PHOSPHATE ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: oxidoreductase, flavoenzyme
• 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: 52562.83

構造登録者

Karplus, P.A.,Schulz, G.E. (登録日: 1992-12-15, 公開日: 1994-01-31, 最終更新日: 2024-06-05)

主引用文献

Karplus, P.A.,Krauth-Siegel, R.L.,Schirmer, R.H.,Schulz, G.E.
Inhibition of human glutathione reductase by the nitrosourea drugs 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea. A crystallographic analysis.
Eur.J.Biochem., 171:193-198, 1988

PubMed Abstract: Glutathione reductase from human erythrocytes was inhibited by incubation with the drugs 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea (HeCNU) under quasi-physiological conditions. For reference purposes, iodoacetamide was used for inactivating alkylation of the enzyme. In each case the modified glutathione reductase was crystallized and its structure determined. These analyses showed that in all experiments the enzyme had reacted at the distal sulfur, that is at the thiol of Cys-58, and virtually nowhere else in the visible structure. The electron density of the HeCNU derivative at 0.3 nm resolution is consistent with a 2-hydroxyethyl group. This alkyl moiety has recently been identified by chemical analysis [Schirmer, R. H., Schöllhammer, T., Eisenbrand, G. and Krauth-Siegel, R. L. (1987) Free Radical Res. Commun. 3, 3-12]. The 0.2 nm resolution electron-density map of the BCNU-derivatized enzyme cannot be explained by a 2-hydroxyethyl group. Instead the modification appears as a carbamoyl moiety containing at least five non-hydrogen atoms. In this derivative the distal cysteine is forced into an unusual conformation.

PubMed: 3338461
DOI: 10.1111/j.1432-1033.1988.tb13775.x

実験手法

X-RAY DIFFRACTION (3 Å)