Inhibitory effect of arginine-derivatives from ginseng extract and basic amino acids on protein-arginine N-methyltransferase

Abstract

Protein-arginine N-methyltransferase (protein methylase I) catalyzes methylation of arginyl residues on substrate protein posttranslationally utilizing S-adenosyl-L-methionine as the methyl donor and yields NG-methylarginine residues. Arginyl-fructose and arginyl-fructosyl-glucose from Korean red ginseng were found to inhibit protein methylase I activity in vitro. This inhibitory activity was shown to be due to arginyl moiety in the molecules, rather than that of carbohydrates. Several basic amino acids as well as polyamines were also found to inhibit protein methylase I activity. Interestingly, the intensity of the inhibitory activity was correlated with the number of amino-group in polyamines, thus, in the order of spermine > spermidine > putrescine > agmatine-sulfate, with IC50 at approximately 15 mM, 25 mM, 35 mM, and 50 mM, respectively. On the other hand, neutral amino acids or NaCl did not inhibit the enzyme activity. Lineweaver-Burk plot analysis of the protein methylase I activity in the presence of arginine and spermidine indicated that the inhibition was competitive in nature in respect to protein substrate, with the Ki values of 24.8 mM and 11.5 mM, respectively.

PRMT3 Is a Distinct Member of the Protein Arginine N-Methyltransferase Family

“…These inconsistencies are perhaps explained by the fact that both high concentrations of Tris and arginine inhibit PRMT activity of recombinant GST fusion proteins, as well as the majority of PRMT activity in RAT1 cell extracts, presumably by competing with arginyl residues within methyl-accepting substrates. Recently, arginine derivatives found in Korean red ginseng as well as other polyamines were shown to effectively inhibit a purified mammalian PRMT activity (41). Although Tris and arginine are relatively poor methylation inhibitors, and free arginine does not appear to be a substrate as determined by thin layer chromatography (data not shown), their suspected mode of action suggests that PRMTs exhibit their substrate affinity toward protonated amino groups.…”

Detection and distribution of arginine derivatives in Panax quinquefolius L. and investigations of their antioxidant properties

“…AFG is generated by heating maltose and Larginine during the process of producing red ginseng. AF and AFG from red ginseng were found to inhibit protein-arginine N-methyltransferase activity (Yool et al, 1999).…”

In Vitro and In Vivo Antihyperglycemic Effect of 2 Amadori Rearrangement Compounds, Arginyl‐Fructose and Arginyl‐Fructosyl‐Glucose

“…In the early stage of Maillard reaction, amadori compounds such as arginyl‐fructosyl‐glucose (AFG) and arginyl‐fructose (AF) (Figure 1) are formed through amadori rearrangement of arginine with glucose or maltose, respectively (Takaku and others 1996; Suzuki and others 2004). AF and AFG are produced during the processing of raw ginseng to red ginseng and their contents are known to be dependent upon the preparation condition of Korean red ginseng (Matsuura and others 1994; Yoo and others 1999; Joo and others 2008). …”