Title

Kinetic mechanism of protein arginine methyltransferase 6 (PRMT6).

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

2-17-2012

Document Type

Article

Medical Subject Headings

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.

Rights and Permissions

Citation: 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

Comments

At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed