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

Date

8-6-2016

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.

Rights and Permissions

Citation: 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

Related Resources

Link to article in PubMed

PubMed ID

27524296