Protein methylation and protein methylases in Leishmania donovani and Leishmania tropica promastigotes.
We studied the content of acid-stable methylated amino acids of soluble proteins in promastigotes of Leishmania donovani and L. tropica. epsilon-N-Trimethyllysine and NG,NG-dimethylarginine were found in both Leishmania species after culture in the presence of [methyl-14C]methionine. In addition, 3-N-methylhistidine was found only in L. tropica and epsilon-N-dimethyllysine only in proteins of L. donovani. As sinefungin, an antileishmanial nucleoside antibiotic, is a known transmethylase inhibitor, its effect on protein methylation was studied, in whole cells and in vitro. In the first case the drug had no effect on the content of methylated amino acid residues of soluble proteins. In vitro, histone methylation by crude extracts was studied at pH 7.2 and 9.0, known in other organisms as optimum pH values for arginine and lysine methylation, respectively. Surprisingly, arginine methylation by extracts of L. donovani was the same at both pH values while lysine residues were more efficiently methylated at pH 7.2 than at pH 9 by the extracts of the two species. These results indicate that the properties of protein methylases I and III of these parasites are different from those of other organisms hitherto studied. The inhibition constants of sinefungin for the leishmanial protein methylases were weak in comparison with those for enzymes from other sources, with the exception of the constant of L. donovani enzyme at pH 9.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007895:Leishmania tropica / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008745:Methylation; D011496:Protein Methyltransferases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000032:analysis / Q000378:metabolism
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D006657:Histones; D011506:Proteins; D011496:Protein Methyltransferases; D000241:Adenosine; C006235:sinefungin