Parasitology Research

, Volume 100, Issue 1, pp 175–181 | Cite as

Responsiveness of parasite Cys His proteases to iron redox

Short Communication

Abstract

Plasmodium falciparum growth can be opposed in erythrocyte culture or in vivo by nonselective inhibitors of CysHis proteases or pro-oxidative drugs, which elevate erythrocyte Fe3+. However, no relationship between Fe redox and CysHis protease inhibition has been suggested. Here, mature falcipain-2 was found to be inhibited by relevant concentrations of Fe3+ but not Fe2+ in the presence of excess GSH or DTT. Initial inhibition of falcipain-2 by Fe3+ (1–50 μM) was reversed in temporal correlation with the 12–14 min half-time of Fe3+ reduction to Fe2+ caused by GSH or DTT (6 mM). The metal–redox responses of cathepsin B from mammal, cruzain from Trypanosoma cruzi, and falcipain-2 from P. falciparum were similar. Fe3+/Fe2+ speciation has features consistent with a natural redox switch modifying the reaction rate of mature CysHis proteases in virtually all cell types. Pro-oxidative antimalarial therapy might intervene in a natural mechanism normally modifying CysHis protease reaction rates via redox state of Fe pools.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Pharmacology and Toxicology, School of MedicineWright State UniversityKetteringUSA

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