Title
Activity-Based Profiling Reveals a Regulatory Link between Oxidative Stress and Protein Arginine Phosphorylation
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology; Program in Chemical Biology
Publication Date
2016-08-06
Document Type
Article
Disciplines
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
Abstract
Protein arginine phosphorylation is a recently discovered modification that affects multiple cellular pathways in Gram-positive bacteria. In particular, the phosphorylation of arginine residues by McsB is critical for regulating the cellular stress response. Given that the highly efficient protein arginine phosphatase YwlE prevents arginine phosphorylation under non-stress conditions, we hypothesized that this enzyme negatively regulates arginine phosphorylation and acts as a sensor of cell stress. To evaluate this hypothesis, we developed the first suite of highly potent and specific SO3-amidine-based YwlE inhibitors. With these protein arginine phosphatase-specific probes, we demonstrated that YwlE activity is suppressed by oxidative stress, which consequently increases arginine phosphorylation, thereby inducing the expression of stress-response genes, which is critical for bacterial virulence. Overall, we predict that these novel chemical tools will be widely used to study the regulation of protein arginine phosphorylation in multiple organisms.
DOI of Published Version
10.1016/j.chembiol.2016.07.008
Source
Fuhrmann J, Subramanian V, Kojetin DJ, Thompson PR. Activity-Based Profiling Reveals a Regulatory Link between Oxidative Stress and Protein Arginine Phosphorylation. Cell Chem Biol. 2016 Aug 6. pii: S2451-9456(16)30237-9. doi:10.1016/j.chembiol.2016.07.008. [Epub ahead of print] PubMed PMID: 27524296. Link to article on publisher's website
Journal/Book/Conference Title
Cell Chemical Biology
Related Resources
PubMed ID
27524296
Repository Citation
Fuhrmann J, Subramanian V, Kojetin DJ, Thompson PR. (2016). Activity-Based Profiling Reveals a Regulatory Link between Oxidative Stress and Protein Arginine Phosphorylation. Thompson Lab Publications. https://doi.org/10.1016/j.chembiol.2016.07.008. Retrieved from https://escholarship.umassmed.edu/thompson/107