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

Protein-arginine N-methyltransferase (protein methylase I) catalyzes methyl ation of arginyl residues on substrate protein posttranslationally utilizin g S-adenosyl-L-methionine as the methyl donor and yields N-G-methylarginine residues. Arginyl-fructose and arginyl-fructosyl-glucose from Korean red g inseng were found to inhibit protein methylase I activity in vitro. This in hibitory activity was shown to be due to arginyl moiety in the molecules, r ather than that of carbohydrates. Several basic amino acids as well as poly amines were also found to inhibit protein methylase I activity. Interesting ly, 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 15mM, 25mM, 35m M, and 50mM, respectively. On the other hand, neutral amino acids or NaCl d id not inhibit the enzyme activity. Lineweaver-Burk plot analysis of the pr otein methylase I activity in the presence of arginine and spermidine indic ated that the inhibition was competitive in nature in respect to protein su bstrate, with the K-i values of 24.8mM and 11.5mM, respectively.