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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2013 May 24; 288(21): 15268.
PMCID: PMC3663546

Trypanosomatid Parasites Exploit an Unusual Enzyme Activation Mechanism in Polyamine Biosynthesis♦

Allosteric Activation of Trypanosomatid Deoxyhypusine Synthase by a Catalytically Dead Paralog

♦ See referenced article, J. Biol. Chem. 2013, 288, 15256–15267

Trypanosomatid parasites cause several fatal human diseases, including African trypanosomiasis, Chagas disease, and leishmaniasis. Collectively, these parasites are rampant in tropical and subtropical regions, with more than 1.3 million new infections and about 70,000 deaths each year. Parasitic polyamines are critical for the infection process: the parasitic polyamine spermidine is a precursor for the hypusine modification of eukaryotic initiation factor 5A. This makes the parasitic polyamine biosynthetic pathway a critical drug target. In this Paper of the Week, Margaret A. Phillips and colleagues at the University of Texas Southwestern Medical Center at Dallas and the University of Dundee in Scotland demonstrated that the two paralogs of deoxyhypusine synthase (DHS) in Trypanosoma brucei were essential for parasitic growth. The investigators showed that one paralog was somewhat catalytically functional and the other was inactive when on its own. However, when the two paralogs formed a heterotetramer, the enzyme activity of the complex increased by 3000-fold. The investigators concluded that functional trypanosomatid DHS is a complex between catalytically impaired and inactive subunits and say, “Our results suggest that this mechanism may be more widely used by trypanosomatids to control enzyme activity and ultimately influence pathogenesis than currently appreciated.”

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Reaction mechanism of DHS.

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