In the human malaria parasite Plasmodium falciparum,polyamines are synthesized by a bifunctional ornithine decarboxylase, S-adenosylmethionine decarboxylase

Muller, Sylke ; Da'dara, Akram ; Luersen, Kai ; Wrenger, Carsten ; Gupta, Robin Das ; Madhubala, Rentala ; Walter, Rolf D. (2000) In the human malaria parasite Plasmodium falciparum,polyamines are synthesized by a bifunctional ornithine decarboxylase, S-adenosylmethionine decarboxylase Journal of Biological Chemistry, 275 (11). pp. 8097-8102. ISSN 0021-9258

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Official URL: http://www.jbc.org/content/275/11/8097.abstract

Related URL: http://dx.doi.org/10.1074/jbc.275.11.8097

Abstract

The polyamines putrescine, spermidine, and spermine are crucial for cell differentiation and proliferation. Interference with polyamine biosynthesis by inhibition of the rate-limiting enzymes ornithine decarboxylase (ODC) andS-adenosylmethionine decarboxylase (AdoMetDC) has been discussed as a potential chemotherapy of cancer and parasitic infections. Usually both enzymes are individually transcribed and highly regulated as monofunctional proteins. We have isolated a cDNA from the malaria parasite Plasmodium falciparumthat encodes both proteins on a single open reading frame, with the AdoMetDC domain in the N-terminal region connected to a C-terminal ODC domain by a hinge region. The predicted molecular mass of the entire transcript is 166 kDa. The ODC/AdoMetDC coding region was subcloned into the expression vector pASK IBA3 and transformed into the AdoMetDC- and ODC-deficient Escherichia coli cell line EWH331. The resulting recombinant protein exhibited both AdoMetDC and ODC activity and co-eluted after gel filtration on Superdex S-200 at ~333 kDa, which is in good agreement with the molecular mass of ~326 kDa determined for the native protein from isolated P. falciparum. SDS-polyacrylamide gel electrophoresis analysis of the recombinant ODC/AdoMetDC revealed a heterotetrameric structure of the active enzyme indicating processing of the AdoMetDC domain. The data presented describe the occurrence of a unique bifunctional ODC/AdoMetDC in P. falciparum, an organization which is possibly exploitable for the design of new antimalarial drugs.

Item Type:Article
Source:Copyright of this article belongs to American Society for Biochemistry and Molecular Biology.
ID Code:29833
Deposited On:23 Dec 2010 04:36
Last Modified:17 May 2016 12:37

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