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

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Summary

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 NaCI 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.

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Abbreviations

AdoMet:

S-adenosyl-L-methionine

PM I:

protein methylase I

Arg-Fru:

arginyl-fructose

Arg-Fru-Glu:

arginyl-fructosyl-glucose

PMSF:

phenylmethylsulfonyl fluoride

MBP:

myelin basic protein

hnRNP:

heterogeneous ribonuclear particle

TCA:

trichloroacetic acid

EDTA:

ethylenediamine tetraacetic acid

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Authors and Affiliations

  1. Department of Biochemistry, Medical School, Korea University, Seoul, Korea

    B. C. Yool, G. H. Park, S. Kim & W. I. Hwang

  2. Graduate School of Biotechnology, Korea University, Seoul, Korea

    G. H. Park & S. Kim

  3. Central Research Laboratory and 2nd Department of Medical Biochemistry, School of Medicine, Ehime University, Japan

    H. Okuda & T. Takaku

Authors
  1. B. C. Yool
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  2. G. H. Park
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  3. H. Okuda
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  4. T. Takaku
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  5. S. Kim
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  6. W. I. Hwang
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Yool, B.C., Park, G.H., Okuda, H. et al. Inhibitory effect of arginine-derivatives from ginseng extract and basic amino acids on protein-arginine N-methyltransferase. Amino Acids 17, 391–400 (1999). https://doi.org/10.1007/BF01361664

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  • DOI: https://doi.org/10.1007/BF01361664

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