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Studies on protein methyltransferase in human cerebrospinal fluid

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Abstract

Protein methyltransferases, rich in most mammalian brains, were studied in human cerebrospinal fluid (CSF). Among several well-characterized groups of methyltransferases, protein methylase I (S-adenosyl-methionine:protein-arginineN-methyltransferase, EC 2.1.1.23) was found in significant amounts in human CSF samples. Both myelin basic protein (MBP)-specific and histone-specific protein methylase I activities were observed, the latter being generally higher in most CSF.S-Adenosyl-l-homocysteine, a potent product inhibitor for the methyltransferase, inhibited approximately 90% of MBP-specific protein methylase I activity at a concentration of 1 mM. The optimum pH of the MBP-specific protein methylase I was found to be around 7.2. Identity of exogenously added MBP as the methylated substrate for CSF enzyme was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An amino acid analysis of the [methyl-3H]protein hydrolysate showed two major radioactive peaks cochromatographing with monomethyl- and dimethyl (symmetric)-arginine. Human CSF contained relatively high endogenous protein methylase I activity (activity measured without added substrate protein): The endogenous substrate can be immunoprecipitated by antibody raised against calf brain MBP. Finally, CSF from several neurological patients were analyzed for protein methylase I, and the results are presented.

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Authors and Affiliations

  1. Fels Research Institute, Temple University School of Medicine, 19140, Philadelphia, PA, USA

    Jongok Park, Woon Ki Paik & Sangduk Kim

  2. Department of Neurology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

    Jeffrey I. Greenstein

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  1. Jongok Park
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  2. Jeffrey I. Greenstein
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  3. Woon Ki Paik
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  4. Sangduk Kim
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Park, J., Greenstein, J.I., Paik, W.K. et al. Studies on protein methyltransferase in human cerebrospinal fluid. J Mol Neurosci 1, 151–157 (1989). https://doi.org/10.1007/BF02918901

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