Open AccessA specific fluorescent probe reveals compromised activity of methionine sulfoxide reductases in Parkinson's disease
Author(s) -
Liangwei Zhang,
Shoujiao Peng,
Jinyu Sun,
Juan Yao,
Jie Kang,
Yuesong Hu,
Jianguo Fang
Publication year - 2017
Publication title -
chemical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.687
H-Index - 172
eISSN - 2041-6539
pISSN - 2041-6520
DOI - 10.1039/c6sc04708d
Subject(s) - methionine sulfoxide reductase , methionine sulfoxide , methionine , biochemistry , enzyme , neurodegeneration , chemistry , fluorescence , sulfoxide , biology , disease , amino acid , medicine , physics , quantum mechanics , organic chemistry , pathology
Oxidation of methionine residues to methionine sulfoxide (MetSO) may cause changes in protein structure and function, and may eventually lead to cell damage. Methionine sulfoxide reductases (Msrs) are the only known enzymes that catalyze the reduction of MetSO back to methionine by taking reducing equivalents from the thioredoxin system, and thus protect cells from oxidative damage. Nonetheless, a lack of convenient assays for the enzymes hampers the exploration of their functions. We report the discovery of Msr-blue, the first turn-on fluorescent probe for Msr with a >100-fold fluorescence increment from screening a rationally-designed small library. Intensive studies demonstrated the specific reduction of Msr-blue by the enzymes. Msr-blue is ready to determine Msr activity in biological samples and live cells. Importantly, we disclosed a decline of Msr activity in a Parkinson's model, thus providing a mechanistic linkage between the loss of function of Msrs and the development of neurodegeneration. The strategy for the discovery of Msr-blue would also provide guidance for developing novel probes with longer excitation/emission wavelengths and specific probes for Msr isoforms.