1887

Abstract

Protein methylases I, II and III were detected in extracts of , and characterized according to the specific amino substituent methylated. Only protein methylase II activity was elevated by difluoromethylornithine treatment of , and hence this enzyme was characterized further. Protein methylase II transferred methyl groups from -adenosyl-l-methionine (-AdoMet) to the carboxyl residues of several protein substrates, exhibiting highest activity with histone VIII-S (arginine-rich subgroup f). The crude enzyme had an apparent for histone VIII-S of 28 mg ml (11.4 mM-aspartyl and 18.4 mM-glutamyl residues methylated), and an apparent for -AdoMet of 8.4 μM. protein methylase II was sensitive to inhibition by -adenosyl-l-homocysteine and its analogue sinefungin with apparent values of 12.9 and 1.6 μm, respectively. Using a partially purified preparation, analysis of kinetic data in the presence and absence of sinefungin indicated that this analogue acts as a competitive inhibitor of the -AdoMet binding site, and as a non-competitive inhibitor of the (protein) histone VIII-S binding site. The possible role of the enzyme in morphological control and its potential as a chemotherapeutic target are discussed.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-137-3-717
1991-03-01
2021-08-06
Loading full text...

Full text loading...

/deliver/fulltext/micro/137/3/mic-137-3-717.html?itemId=/content/journal/micro/10.1099/00221287-137-3-717&mimeType=html&fmt=ahah

References

  1. AviLA J. L. , Avila A. . 1987; Correlation of sinefungin susceptibility and drug-affinity for protein carboxymethyltransferase activity in American Leishmania species.. Molecular and Biochemical Parasitology 26 69 76
    [Google Scholar]
  2. Bacchi C. J. , McCann P. P. . 1987; Parasitic protozoa and polyamines.. Inhibition of Polyamine Metabolism 317 344 P. P. McCann , A. E. Pegg , A. Sjoerdsma. . New York: Academic Press;
    [Google Scholar]
  3. Bacchi C. J. , Garofalo J. , Mockenhaupt D. , McCann P. P. , Diekema K. A. , Pegg A. E. , Nathan H. C , Mullaney E. A. , Chunosoff L. T. , Sjoerdsma A. , Hutner S. H. . 1983; In vivo effects of dl-α-difluoromethylornithine on the metabolism and morphology of Trypanosoma brucei brucei.. Molecular and Biochemical Parasitology 7 209 225
    [Google Scholar]
  4. Bacchi C. J. , Berens R. L. , Nathan H. C , Klein R. S. , Elegbe I. A. , Rao K. V. B. , McCann P. P. , Marr J. J. . 1987; Synergism between 9-deazainosine and dl-α-difluoromethylornithine in treatment of experimental African trypanosomiasis.. Antimicrobial Agents and Chemotherapy 31 1406 1413
    [Google Scholar]
  5. Bachrach U. , Schnur L. F. , El-On J. , Greenblatt C. L. , Pearlman E. , Robert-Gero M. , Lederer M. . 1980; Inhibitory action of sinefungin and SIB A (5′-deoxy-5′-S-isobutylthioadenosine) on the growth of promastigotes and amastigotes of different species of Leishmania.. FEBS Letters 121 287 291
    [Google Scholar]
  6. Bernards A. , van Harten-Loosbroek N. , Borst P. . 1984; Modification of telomeric DNA in Trypanosoma brucei; a role in antigenic variation?. Nucleic Acids Research 12 4153 4170
    [Google Scholar]
  7. Bienen E. J. , Hill G. C. , Shin K. O. . 1983; Elaboration of mitochondrial function during Trypanosoma brucei differentiation.. Molecular and Biochemical Parasitology 7 75 86
    [Google Scholar]
  8. Blanchard P. , Dodic N. , Fourrey J. L. , Geze M. , Lawrence F. , Malina H. , Paolantonacci P. , Vedel M. , Tempete C , Robert-Gero M. , Lederer E. . 1986; Sinefungin and derivatives: synthesis, biosynthesis and molecular target studies in Leishmania.. Biological Methylation and Drug Design 435 446 R. T. Borchardt , C. R. Creveling , P. M. Ueland . Clifton: The Humana Press;
    [Google Scholar]
  9. Diliberto E. J. , Axelrod J. . 1974; Characterization and substrate specificity of a protein carboxymethylase in the pituitary gland.. Proceedings of the National Academy of Sciences of the United States of America 71 1701 1704
    [Google Scholar]
  10. Dube D. K. , Mpimbaza G. , Allison A. C , Lederer E. , Rovis L. . 1983; Antitrypanosomal activity of sinefungin.. American Journal of Tropical Medicine and Hygiene 32 31 33
    [Google Scholar]
  11. Duschak V. G. , Cazzulo J. J. . 1990; The histones of the insect trypanosomatid, Crithidia fasciculata.. Biochimica et Biophysica Acta 1040 159 166
    [Google Scholar]
  12. Fairlamb A. , Henderson G. B. , Bacchi C. J. , Cerami A. . 1987; In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei.. Molecular and Biochemical Parasitology 24 185 192
    [Google Scholar]
  13. Feagin J. E. , Jasmer D. P. , Stuart K. . 1986; Differential mitochondrial gene expression between slender and stumpy blood-forms of Trypanosoma brucei.. Molecular and Biochemical Parasitology 20 207 214
    [Google Scholar]
  14. Fieser L. F. , Fieser M. . 1963 Advanced Organic Chemistry New York: Reinhold;
    [Google Scholar]
  15. Fuller R. W. , Nagarajan R. . 1978; Inhibition of methyltransfer-ases by some new analogs of S-adenosylhomocysteine.. Biochemical Pharmacology 27 1981 1983
    [Google Scholar]
  16. De Gee A. L. W. , Carsten P. H. B. , McCann P. P. , Mansfield J. M. . 1984; Morphological changes in Trypanosoma brucei rhodesiense following inhibition of polyamine biosynthesis in vivo . Tissue and Cell 16 731 738
    [Google Scholar]
  17. Giffin B. F. , McCann P. P. . 1989; Physiological activation of the mitochondrion and the transformation capacity of DFMO-induced intermediate and short stumpy bloodstream form trypanosomes.. American Journal of Tropical Medicine and Hygiene 40 487 493
    [Google Scholar]
  18. Giffin B. F. , McCann P. P. , Bitonti A. J. , Bacchi C. J. . 1986; Polyamine depletion following exposure to dl-α-difluoromethylor-nithine both in vivo and in vitro initiates morphological alterations and mitochondrial activation in a monomorphic strain of Trypanosoma brucei brucei . Journal of Protozoology 33 238 243
    [Google Scholar]
  19. Haklai R. , Kloog Y. . 1990; Carboxyl methylation of 21-23 kDa membrane proteins in intact neuroblastoma cells is increased with differentiation.. FEBS Letters 259 233 236
    [Google Scholar]
  20. Kim S. . 1977; Enzymatic esterification of proteins.. The Biochemistry of Adenosylmethionine 415 434 F. Salvatore , E. Borek , V. Zappia , H. G. Williams-Ashman , F. Schlenk . New York: Columbia University Press;
    [Google Scholar]
  21. Kim S. , Paik W. K. . 1970; Purification and properties of protein methylase II.. Journal of Biological Chemistry 245 1806 1813
    [Google Scholar]
  22. Kloog Y. , Axelrod J. , Spector I. . 1983; Protein carboxylmethy-lation increases in parallel with differentiation of neuroblastoma cells.. Journal of Neurochemistry 40 522 529
    [Google Scholar]
  23. Lanham S. M. , Godfrey D. G. . 1970; Isolation of salivarian trypanosomes from man and other animals using DEAE cellulose.. Experimental Parasitology 28 521 523
    [Google Scholar]
  24. Nadler J. P. , Lederer E. , Wittner M. , Baum S. G. , Tanowitz H. B. . 1982; The effect of adenosine analogues on the in vitro growth of Trypanosoma cruzi.. Transactions of the Royal Society of Tropical Medicine and Hygiene 76 285 287
    [Google Scholar]
  25. Nolan L. . 1987; Molecular target of the antileishmanial action of sinefungin.. Antimicrobial Agents and Chemotherapy 31 1542 1548
    [Google Scholar]
  26. Paik W. K. , Kim S. . 1968; Protein methylase I. Purification and properties of the enzyme. Journal of Biological Chemistry 243 2108 2114
    [Google Scholar]
  27. Paik W. K. , Kim S. . 1969; Enzymatic methylation of histones.. Archives of Biochemistry and Biophysics 134 632 637
    [Google Scholar]
  28. Paik W. K. , Kim S. . 1970; Solubilization and partial purification of protein methylase III from calf thymus nuclei.. Journal of Biological Chemistry 245 6010 6015
    [Google Scholar]
  29. Paik W. K. , Kim S. . 1980 Protein Methylation Chichester: John Wiley;
    [Google Scholar]
  30. Paik W. K. , Lee H. W. , Morris H. P. . 1972; Protein methylases in hepatomas.. Cancer Research 32 37 40
    [Google Scholar]
  31. Paik M. K. , Hwang B. D. , Lim K. . 1988; Human placenta S-adenosylmethionine protein carboxyl O-methyltransferase (protein methylase II), purification and characterization.. International Journal of Biochemistry 20 1107 1112
    [Google Scholar]
  32. Paolantonacci P. , Lawrence F. , Robert-Gero M. . 1985; Differential effect of sinefungin and its analogs on the multiplication of three Leishmania species.. Antimicrobial Agents and Chemotherapy 28 528 531
    [Google Scholar]
  33. Paolantonacci P. , Lawrence F. , Nolan L. , Robert-Gero M. . 1986; Protein methylation and protein methylases in Leishmania donovani and Leishmania tropica promastigotes.. Molecular and Biochemical Parasitology 21 47 54
    [Google Scholar]
  34. Paolantonacci P. , Lawrence F. , Nolan L. L. , Robert-Gero M. . 1987; Inhibition of leishmanial DNA synthesis by sinefungin.. Biochemical Pharmacology 36 2813 2820
    [Google Scholar]
  35. Pays E. , Delauw M. F. , Laurent M. , Steinert M. . 1984; Possible DNA modification in GC dinucleotides of Trypanosoma brucei telomeric sequences; relationship with antigen gene transcription.. Nucleic Acids Research 12 5235 5247
    [Google Scholar]
  36. Penketh P. G. , Krishnamurthy S. , Divo A. A. , Patton C. L. , Sartorelli A. C. . 1990; Methylating agents as trypanocides.. Journal of Medicinal Chemistry 33 730 732
    [Google Scholar]
  37. Perry K. L. , Watkins K. P. , Agabian N. . 1987; Trypanosome mRNAs have unusual 'Cap 4' structures acquired by addition of a spliced leader.. Proceedings of the National Academy of Sciences of the .United States of America 84 8190 8194
    [Google Scholar]
  38. Robbins E. , Boron T. W. . 1967; The cytoplasmic synthesis of histones in HeLa cells and its temporal relationship to DNA replication.. Proceedings of the National Academy of Sciences of the United States of America 57 409 416
    [Google Scholar]
  39. Rojas M. V. , Galanti N. . 1990; DNA methylation in Trypanosoma cruzi.. FEBS Utters 263 113 116
    [Google Scholar]
  40. Shepherd G. R. , Hardin J. M. , Noland B. J. . 1971; Methylation of lysine residues of histone fractions in synchronized mammalian cells.. Archives of Biochemistry and Biophysics 143 1 5
    [Google Scholar]
  41. Tidwell T. , Allfrey V. G. , Mirsky A. E. . 1968; The methylation of histones during regeneration of liver.. Journal of Biological Chemistry 243 707 715
    [Google Scholar]
  42. Trivedi L. , Gupta A. , Paik W. K. , Kim S. . 1982; Purification and properties of protein methylase II from wheat germ.. European Journal of Biochemistry 128 349 354
    [Google Scholar]
  43. Ueland P. M. . 1982; Pharmacological and biochemical aspects of S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase.. Pharmacology Reviews 34 223 253
    [Google Scholar]
  44. van Waarde A. . 1987; What is the function of protein carboxyl methylation?. Comparative Biochemistry and Physiology 86B 423 438
    [Google Scholar]
  45. van Waarde A. , van Hoof P. J. M. . 1985; Pitfalls in the measurement of protein carboxyl methylation during chemotaxis of Dictyostelium discoideum.. Biochimica et Biophysica Acta 840,344 354
    [Google Scholar]
  46. Yarlett N. , Bacchi C. J. . 1988; Effect of dl-α-difluoromethyl-ornithine on methionine cycle intermediates in Trypanosoma brucei brucei.. Molecular and Biochemical Parasitology 27 1 10
    [Google Scholar]
  47. Zukerman S. H. , O’Dea R. F. , Olson J. M. , Douglas D. S. . 1982; Protein carboxylmethylation during in vitro culture of human peripheral blood monocytes and pulmonary alveolar macrophages.. Molecular Immunology 19 281 286
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-137-3-717
Loading
/content/journal/micro/10.1099/00221287-137-3-717
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error