Putrescine activated S-adenosylmethionine decarboxylase from Trypanosoma brucei brucei

Babu L. Tekwani, Cyrus J. Bacchi, Anthony Pegg

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Trypanosoma brucei brucei contained a S-adenosyl-L-methionine decarboxylase (AdoMetDC) strongly activated by putrescine. The enzyme was also activated to a lesser extent by cadaverine and 1,3-diaminopropane. Spermidine and spermine had no effect on basal activity of the enzyme. However, they interfered with putrescine activation of trypanosomal AdoMetDC. The trypanosomal enzyme could not be precipitated with antiserum against human AdoMetDC. The trypanosomal AdoMetDC enzyme subunit was labeled by reaction with 35S-decarboxylated AdoMet in the presence of NaCNBH4, and found to have a molecular weight of 34 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The subunit was readily degraded on storage to a form with a molecular weight of 26 kDa. The specificity of labeling of AdoMetDC by this procedure was confirmed by the prevention of 35S-decarboxylated S-adenosylmethionine (AdoMet) binding in the presence of specific AdoMetDC inhibitors [either methylglyoxal bis(guanylhydrazone (MGBG), a reversible inhibitor, or 5′-deoxy-5′-[(2-hydrazinoethyl)methylamino]adenosine (MHZEA), an irreversible inactivator]. As compared to human AdoMetDC, the trypanosomal enzyme showed weaker binding to a column of MGBG-Sepharose and also was significantly less sensitive to inhibition by MGBG and its congener ethylglyoxal bis(guanylhydrazone) (EGBG). Thus, the trypanosomal AdoMetDC differs significantly from its mammalian and bacterial counterparts and may therefore be exploited as a specific target for chemotherapy of trypanosomiasis.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume117
Issue number1
DOIs
StatePublished - Mar 1992

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Putrescine activated S-adenosylmethionine decarboxylase from Trypanosoma brucei brucei'. Together they form a unique fingerprint.

  • Cite this