Title
Kinetic mechanism of protein arginine methyltransferase 6 (PRMT6).
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
2012-02-17
Document Type
Article
Subjects
Amino Acid Sequence; Biocatalysis; Drug Discovery; Enzyme Inhibitors; Humans; Kinetics; Nuclear Proteins; Peptides; Protein-Arginine N-Methyltransferases
Disciplines
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
Abstract
The protein arginine methyltransferases (PRMTs) are a family of enzymes that catalyze the mono- and dimethylation of arginine residues in a variety of proteins. Although these enzymes play important roles in a variety of cellular processes, aberrant PRMT activity is associated with several disease states, including heart disease and cancer. In an effort to guide the development of inhibitors targeting individual PRMTs, we initiated studies to characterize the molecular mechanisms of PRMT catalysis. Herein, we report studies on the kinetic mechanism of PRMT6. Initial velocity, product inhibition, and dead-end analog inhibition studies with the AcH4-21 and R1 peptides, as well as their monomethylated versions, indicate, in contrast to a previous report, that PRMT6 utilizes a rapid equilibrium random mechanism with dead-end EAP and EBQ complexes.
DOI of Published Version
10.1074/jbc.M111.333609
Source
J Biol Chem. 2012 Feb 17;287(8):6062-71. doi: 10.1074/jbc.M111.333609. Epub 2012 Jan 3. Link to article on publisher's site
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
Repository Citation
Obianyo, Obiamaka and Thompson, Paul R., "Kinetic mechanism of protein arginine methyltransferase 6 (PRMT6)." (2012). Thompson Lab Publications. 39.
https://escholarship.umassmed.edu/thompson/39
Comments
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.