Specific and nonhomologous isofunctional enzymes of the genetic information processing pathways as potential therapeutical targets for tritryps

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.

Figure 1

Venn diagram of shared enzymatic activities between the Tritryps. Yellow: L. major unique ECs; red: T. cruzi unique ECs; blue: T. brucei unique ECs; orange: between T. cruzi and T. brucei; green: between L. major and T. brucei; purple: between T. cruzi and L. major; gray: between all Tritryps.

Figure 2

Aminoacyl-tRNA biosynthesis map. Gray boxes represent enzymes identified by AnEnPi for the Tritryps. White boxes are those that were not identified by KEGG neither by AnEnPi. Blue star: ECs identified by KEGG for the Tritryps. Red star: ECs identified by KEGG for L. major and T. brucei. Modified from http://www.genome.jp/kegg/pathway/map/map00970.html.