Structural Characterization of the interaction between divalent cations and the novel Schistosoma mansoni Universal Stress Protein G4LZI3

Abstract
Approximately 200 000 people in sub-Saharan Africa lose their lives to schistosomiasis every year. This coupled with other severe Neglected Tropical Diseases, HIV/AIDS, malaria, tuberculosis and poverty, does not make the situation any better. Vaccines targeting this disease are still yet to be discovered and current treatment is becoming a problem as drug resistance has been reported. Thus, looking for an alternative treatment regimen is fast becoming a priority. This study took an interest in Universal Stress Proteins and focused on a novel G4LZI3 USP, which has been put forward as a possible candidate vaccine. A sufficient amount (0.518mg/ml) of recombinant G4LZI3 protein was successfully expressed using 0.5mM IPTG and subjected to a Nickel-NTA column for purification. The fractions were pooled together, concentrated down and used to investigate the binding of the protein with 3 metallic divalent cations using Isothermal Titration Calorimetry (ITC). Additionally, bioinformatics was employed to predict the secondary structure of the protein, generate a 3-dimensional model of the protein and use it for docking the divalent cations. Moreover, the interacting partners of the G4LZI3 protein were determined, thus giving a clue towards the function of the protein. Bioinformatics tools assisted in confirming Ca2+, Mg2+ and Zn2+ as putative ligands and additionally identified ATP, AMP and U20 as possible molecules that interact with the G4LZI3 USP protein. However, in vivo studies only showed interaction between Mg2+ and the protein. These results provide prospects for future studies toward drug discovery for schistosomiasis.
Description
A dissertation submitted to the Faculty of Science and Agriculture in fulfillment of the requirements for the Degree of Master of Science (MSc) in Biochemistry in the Department of Biochemistry and Microbiology at the University of Zululand, 2017
Keywords
docking --isothermal titratiuon calorimetry --neglected tropical deisease --praziquantel --Schistosoma mansoni --universal stress protein
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