Abstract
Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryps) are unicellular protozoa that cause leishmaniasis, sleeping sickness and Chagas' disease, respectively. Most drugs against them were discovered through the screening of large numbers of compounds against whole parasites. Nonhomologous isofunctional enzymes (NISEs) may present good opportunities for the identification of new putative drug targets because, though sharing the same enzymatic activity, they possess different three-dimensional structures thus allowing the development of molecules against one or other isoform. From public data of the Tritryps' genomes, we reconstructed the Genetic Information Processing Pathways (GIPPs). We then used AnEnPi to look for the presence of these enzymes between Homo sapiens and Tritryps, as well as specific enzymes of the parasites. We identified three candidates (ECs 3.1.11.2 and 6.1.1.-) in these pathways that may be further studied as new therapeutic targets for drug development against these parasites.
Highlights
Nonhomologous isofunctional enzymes (NISEs) may present good opportunities for the identification of new putative drug targets because, though sharing the same enzymatic activity, they possess different threedimensional structures allowing the development of molecules against one or other isoform
Recent estimates indicate that more than one billion people, living in tropical and subtropical regions of developing countries, are at the risk of contracting diseases caused by the protozoans Leishmania major, Trypanosoma brucei and Trypanosoma cruzi [1,2,3]
We employed computational methods to identify specific and nonhomologous isofunctional enzymes in the genetic information processing pathways of the Tritryps, enzymes that could serve as interesting candidates for further studies aiming at their validation as drug targets
Summary
Recent estimates indicate that more than one billion people, living in tropical and subtropical regions of developing countries, are at the risk of contracting diseases (which are mostly endemic at these places) caused by the protozoans Leishmania major, Trypanosoma brucei and Trypanosoma cruzi [1,2,3]. Enzyme Research the drawing of the biological system to the generation of testable hypotheses about the structure and working of the pathway and from the elucidation of complex properties not inferred by the simple description of the individual components to the recognition of potential drug targets against pathogenic organisms via the identification of essential steps in these processes [16]. Analyses of genomic data from L. major, T. brucei, and T. cruzi have provided a global view of the proteincoding genes that produce enzymes belonging to important pathways through the identification of several processes in common between these parasites and other species.
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