Metronidazole, a 5-nitroimidazole drug, has been the gold standard for several decades in the treatment of infections with microaerophilic protist parasites, including Entamoeba histolytica. For activation, the drug must be chemically reduced, but little is known about the targets of the active metabolites. Applying two-dimensional gel electrophoresis and mass spectrometry, we searched for prot...

Plasmodium falciparum, the causative agent of severe human malaria. The dominance of resistant strains has compelled to the discovery and development of new and different modes-ofaction. Current plasmodial drug discovery efforts remains lack far-reaching set of legitimated drug targets. Prerequisite of these targets (or the pathways in which they function) is that they prove to be crucial for p...

Purified calf thymus ribonucleoside-diphosphate reductase (2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1), showed an absolute requirement for a dithiol as hydrogen donor, whereas the natural monothiol glutathione (GSH) was inactive per se. However, a protein partially purified from thymus coupled the oxidation of GSH to the formation of deoxyribonucleoti...

The crystal structures of three forms of Escherichia coli thioredoxin reductase have been refined: the oxidized form of the wild-type enzyme at 2.1 A resolution, a variant containing a cysteine to serine mutation at the active site (Cys138Ser) at 2.0 A resolution, and a complex of this variant with nicotinamide adenine dinucleotide phosphate (NADP+) at 2.3 A resolution. The enzyme mechanism inv...

The thioredoxin system, comprising thioredoxin (Trx), thioredoxin reductase (TrxR) and NADPH, is one of the major cellular antioxidant systems, implicated in a large and growing number of biological functions. Trx acts as an oxidoreductase via a highly conserved dithiol/disulfide motif located in the active site ( Trp-Cys-Gly-Pro- Cys-Lys-). Different factors are involved in the regulation of T...

Ribonucleoside diphosphate reductase consists of two nonidentical subunits, proteins Bl and B2. The enzyme catalyzes the reduction of ribonucleotides to the corresponding deoxyribonucleotides. The electrons required in this reduction are transported from NADPH via a flavoprotein, thioredoxin reductase, to a low molecular weight protein, thioredoxin. The reduced form of thioredoxin acts as hydro...

Nicotinamide cofactor-dependent oxidoreductases have become a valuable tool for the synthesis of high value chiral compounds. The feasibility biocatalytic processes involving these enzymes stands and falls with efficiency regeneration cofactors. In this study, we describe novel NADPH method based on natural thioredoxin electron delivery system. Thioredoxin 1 (Trx1) reductase (TR) from Thermus t...

Myeloperoxidase produces strong oxidants during the immune response to destroy invading pathogens. However, these oxidants can also cause tissue damage, which contributes to the development of numerous inflammatory diseases. Selenium containing compounds, including selenomethionine (SeMet) and 1,4-anhydro-5-seleno-D-talitol (SeTal), react rapidly with different MPO-derived oxidants to form the ...

In P. falciparum, antioxidant proteins of the glutathione and thioredoxin systems are compartmentalized. Some subcellular compartments have only a partial complement of these proteins. This lack of key anti-oxidant proteins in certain sub-cellular compartments might be compensated by functional complementation between these systems. By assessing the cross-talk between these systems, we show for...