1grh
From Proteopedia
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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
Overview
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., Schollhammer, 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.
About this Structure
1GRH is a Protein complex structure of sequences from [1] with CYS and EOH as ligands. Full crystallographic information is available from OCA.
Reference
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., Karplus PA, Krauth-Siegel RL, Schirmer RH, Schulz GE, Eur J Biochem. 1988 Jan 15;171(1-2):193-8. PMID:3338461
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