Glutathione Reductase Activity With an Oxidized Methylated Glutathione Analog
Document Type
Article
Publication Date
7-1-2013
Department
Chemistry and Biochemistry
School
Mathematics and Natural Sciences
Abstract
The activity of glutathione reductase with an unnatural analog of oxidized glutathione was explored. The analog, L-γ-glutamyl-2-methyl-L-cysteinyl-glycine disulfide, places an additional methyl group on the alpha position of each of the central cysteine residues, which significantly increases steric bulk near the disulfide bond. Glutathione reductase was completely unable to catalyze the sulfur-sulfur bond reduction of the analog. Additionally, enzyme kinetics experiments indicated that the analog acts as a competitive inhibitor of glutathione reductase. Computational studies confirm that the methylated analog fits within the active site of the enzyme but its disulphide bond geometry is altered, preventing reduction by the enzyme. The substitution of (R)-2-methylcysteine in place of natural (R)-cysteine in peptides constitutes a new strategy for stabilizing disulphide bonds from enzyme-catalyzed degradation. © 2014 Informa UK Ltd.
Publication Title
Journal of Enzyme Inhibition and Medicinal Chemistry
Volume
29
Issue
4
First Page
491
Last Page
494
Recommended Citation
Kedrowski, B.,
Gutow, J.,
Stock, G.,
Smith, M.,
Jordan, C.,
Masterson, D.
(2013). Glutathione Reductase Activity With an Oxidized Methylated Glutathione Analog. Journal of Enzyme Inhibition and Medicinal Chemistry, 29(4), 491-494.
Available at: https://aquila.usm.edu/fac_pubs/20149