Characterizing protein kinase translation initiation factor 2 of Trypanosoma cruzi

• Grant number: 16/20743-6
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2016
• Effective date (End): October 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal researcher: Sergio Schenkman
• Grantee: Matheus Monteiro da Silva
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 15/22031-0 - Cell signaling in Trypanosoma during host-parasite interaction, AP.TEM

Abstract

We have previously found in our laboratory that gene knockout of a protein kinase (TcK2) that phosphorylate the eukaryotic translation initiation factor 2 (eIF2) affects growth of Trypanosoma cruzi, a protozoan parasite that causes Chagas disease. Therefore, TcK2 can be a drug target for Chagas' disease treatment. This enzyme is similar to protein kinase 3 of mammals (PERK) to which inhibitors were developed for the treatment of tumors. In this project, we intend to evaluate the action of developed inhibitors for PERK in T. cruzi enzyme activity. We propose in this project: 1) To generate a recombinant protein based on the sequence of the catalytic domain of protein kinase TcK2 fused to glutathione S-transferase (GST) and test it for kinase activity. 2) To examine the effect of different compounds on the activity of the recombinant kinase. 3) To test the compounds with inhibitory capacity in the autophosphorylation of TcK2 in the parasite. 4) To check whether the compounds affect the proliferation of parasites. (AU)