Title
Activity-based protein profiling of protein arginine methyltransferase 1
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
2011-10-21
Document Type
Article
Subjects
Breast Neoplasms; Cell Line, Tumor; *Drug Design; Enzyme Inhibitors; Female; Humans; Inhibitory Concentration 50; Protein-Arginine N-Methyltransferases; Repressor Proteins
Disciplines
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
Abstract
The protein arginine methyltransferases (PRMTs) are SAM-dependent enzymes that catalyze the mono- and dimethylation of peptidyl arginine residues. PRMT1 is the founding member of the PRMT family, and this isozyme is responsible for methylating approximately 85% of the arginine residues in mammalian cells. Additionally, PRMT1 activity is aberrantly upregulated in heart disease and cancer. As a part of a program to develop isozyme-specific PRMT inhibitors, we recently described the design and synthesis of C21, a chloroacetamidine bearing histone H4 tail analogue that acts as an irreversible PRMT1 inhibitor. Given the covalent nature of the interaction, we set out to develop activity-based probes (ABPs) that could be used to characterize the physiological roles of PRMT1. Herein, we report the design, synthesis, and characterization of fluorescein-conjugated C21 (F-C21) and biotin-conjugated C21 (B-C21) as PRMT1-specific ABPs. Additionally, we provide the first evidence that PRMT1 activity is negatively regulated in a spatial and temporal fashion.
DOI of Published Version
10.1021/cb2001473
Source
ACS Chem Biol. 2011 Oct 21;6(10):1127-35. doi: 10.1021/cb2001473. Epub 2011 Aug 23. Link to article on publisher's site
Journal/Book/Conference Title
ACS chemical biology
Related Resources
Repository Citation
Obianyo O, Causey CP, Jones JE, Thompson PR. (2011). Activity-based protein profiling of protein arginine methyltransferase 1. Thompson Lab Publications. https://doi.org/10.1021/cb2001473. Retrieved from https://escholarship.umassmed.edu/thompson/43
Comments
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.