Logo image
Metabolic Synthesis of Clickable Glutathione for Chemoselective Detection of Glutathionylation
Journal article   Peer reviewed

Metabolic Synthesis of Clickable Glutathione for Chemoselective Detection of Glutathionylation

Kusal T. G. Samarasinghe, Dhanushka N. P. Munkanatta Godage, Garrett C. VanHecke and Young-Hoon Ahn
Journal of the American Chemical Society, v 136(33), pp 11566-11569
20 Aug 2014
PMID: 25079194

Abstract

Chemistry Chemistry, Multidisciplinary Physical Sciences Science & Technology
Glutathionylation involves reversible protein cysteine modification that regulates the function of numerous proteins in response to redox stimuli, thereby altering cellular processes. Herein we developed a selective and versatile approach to identifying glutathionylation by using a mutant of glutathione synthetase (GS). GS wildtype catalyzes coupling of gamma Glu-Cys to Gly to form glutathione. We generated a GS mutant that catalyzes azido-Ala in place of Gly with high catalytic efficiency and selectivity. Transfection of this GS mutant (F152A/S151G) and incubation of azido-Ala in cells efficiently afford the azide-containing glutathione derivative, gamma Glu-Cys-azido-Ala. Upon H2O2 treatment, clickable glutathione allowed for selective and sensitive detection of glutathionylated proteins by Western blotting or fluorescence after click reaction with biotin-alkyne or rhodamine-alkyne. This approach affords the efficient metabolic tagging of intracellular glutathione with small clickable functionality, providing a versatile handle for characterizing glutathionylation.

Metrics

8 Record Views
45 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Chemistry, Multidisciplinary
Logo image