PRMT1 is one of nine currently known protein arginine methyltransferases, which transfer the methyl group from S-adenosylmethionine (SAM) to arginine residues of the substrate. Arginine methylation is involved in a vast range of cellular processes, and its dysfunction has been implicated to a number of pathological conditions, including cancer, diabetes and heart disease, thus PRMT1 regulation is a topic of interest. Using kinetic assays we have shown that PRMT1 activity is markedly lower in oxidized versus reduced samples. We have also determined that the SAM dissociation constant of oxidized samples is roughly twofold higher than in reduced samples, and that the binding of SAM is more than twenty times faster in reduced samples than in oxidized samples. The kinetic properties of PRMT1 are thought to be owed, in part, to the oligomeric state of the enzyme. Our studies indicate that the oligomeric state of PRMT1 is also influenced by the presence of reductant. PRMT1 samples treated with reductant were analyzed via size exclusion chromatography and shown to form smaller oligomers than untreated samples. However, a cysteine-less PRMT1 mutant does not exhibit redox dependent effects on activity or oligomerization. Based on these initial studies it seems likely that a cysteine residue is causing the effects we have observed. We are currently working to discover which cysteine(s) is responsible for these effects. This knowledge will provide a foundation for further research into the kinetic mechanism of PRMT1 and may lead to the development of novel therapeutic pathways.

Investigation into the kinetics and oligomerization of PRMT1

247th National Meeting (2014)

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