Chaugas Disease Research Paper
Chagas disease is a public health problem in Latin America with a great impact in Brazil. The latest estimates show that about seven million people in the world are infected by the kinetoplastid protozoa Trypanosoma cruzi (1). In spite of this, there are no vaccines against Chagas Disease (2). The current drugs used for treating this disease are effective only in the acute phase, with limited efficacy in the chronic stage of the disease and many toxic side effects (3) (4). Therefore, there is an urgent need for the development of new drugs more effective than the traditional treatment and less toxic to humans. For this purpose, new therapeutic targets with critical importance in the metabolism of the parasite and the absence of structurally
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In sum, analogous enzymes differ in their primary and tertiary structures, but have the same enzymatic functions. The analogy usually happens due to different origins of genes encoding the enzymes in question, which have the same enzymatic function by an evolutionary phenomenon of convergence (5)(6)(7). An important tool in the search for such enzymes is the Anenpi: a bioinformatic tool that, besides other functionalities, predicts analogy and specificity between enzymes of distinct organisms …show more content…
cruzi (TcRpi) and H. sapiens (HsRpi) are analogous enzymes (9), as previously shown as Anenpi's results. The Rpi enzymes can be divided into two protein families: type A and type B, which are analogues to each other. The Rpi of T. cruzi (TcRpi) belongs to the family of the type B Rpis generally encountered in prokaryotes and lower eukaryotes. On the other hand, the HsRpi belongs to the type A family of Rpis, which has representatives in most eukaryotes, as well as in prokaryotes. The type A Rpis are not present in trypanosomatids (10) (11). Besides, the Rpi plays a central role in the pentose phosphate pathway (PPP) that is responsible for the production of nucleotide precursors and NADPH. The latter one is critical for the protection of trypanosomatids against oxidative stress and for biosynthetic reactions. In the PPP, the Rpi enzyme catalyzes the reversible isomerization reaction between D-ribose-5-phosphate (R5P) and D-ribulose-5-phosphate (Ru5P) (12) (13) (14)
In sum, analogous enzymes differ in their primary and tertiary structures, but have the same enzymatic functions. The analogy usually happens due to different origins of genes encoding the enzymes in question, which have the same enzymatic function by an evolutionary phenomenon of convergence (5)(6)(7). An important tool in the search for such enzymes is the Anenpi: a bioinformatic tool that, besides other functionalities, predicts analogy and specificity between enzymes of distinct organisms …show more content…
cruzi (TcRpi) and H. sapiens (HsRpi) are analogous enzymes (9), as previously shown as Anenpi's results. The Rpi enzymes can be divided into two protein families: type A and type B, which are analogues to each other. The Rpi of T. cruzi (TcRpi) belongs to the family of the type B Rpis generally encountered in prokaryotes and lower eukaryotes. On the other hand, the HsRpi belongs to the type A family of Rpis, which has representatives in most eukaryotes, as well as in prokaryotes. The type A Rpis are not present in trypanosomatids (10) (11). Besides, the Rpi plays a central role in the pentose phosphate pathway (PPP) that is responsible for the production of nucleotide precursors and NADPH. The latter one is critical for the protection of trypanosomatids against oxidative stress and for biosynthetic reactions. In the PPP, the Rpi enzyme catalyzes the reversible isomerization reaction between D-ribose-5-phosphate (R5P) and D-ribulose-5-phosphate (Ru5P) (12) (13) (14)