Biochemical characterisation and novel classification of monofunctional S-adenosylmethionine decarboxylase of Plasmodium falciparum

Research output: Contribution to journalArticle

Abstract

Plasmodium falciparum like other organisms is dependent on polyamines for proliferation. Polyamine biosynthesis in these parasites is regulated by a unique bifunctional S-adenosylmethionine decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC). Only limited biochemical and structural information is available on the bifunctional enzyme due to the low levels and impurity of an instable recombinantly expressed protein from the native gene. Here we describe the high level expression of stable monofunctional PfAdoMetDC from a codon-harmonised construct, which permitted its biochemical characterisation indicating similar catalytic properties to AdoMetDCs of orthologous parasites. In the absence of structural data, far-UV CD showed that at least on secondary structure level, PfAdoMetDC corresponds well to that of the human protein. The kinetic properties of the monofunctional enzyme were also found to be different from that of PfAdoMetDC/ODC as mainly evidenced by an increased K-m. We deduced that complex formation of PfAdoMetDC and PfODC could enable coordinated modulation of the decarboxylase activities since there is a convergence of their k(cat) and lowering of their K-m. Such coordination results in the aligned production of decarboxylated AdoMet and putrescine for the subsequent synthesis of spermidine. Furthermore, based on the results obtained in this study we propose a new AdoMetDC subclass for plasmodial AdoMetDCs. (C) 2011 Elsevier B.V. All rights reserved.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology

Keywords

  • Codon-harmonize, S-adenosylmethionine decarboxylase, Malaria, Oligomerization, Polyamines
Original languageEnglish
Pages (from-to)17-26
JournalMolecular and Biochemical Parasitology
Volume180
Issue number1
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes

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