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

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.

Grantor dc:publisher.institution

University of Zululand

Year dc:date.issued

2017

Author dc:creator

• Masamba, Priscilla

Advisor dc:contributor.advisor

• Kappo, A.P

• docking --isothermal titratiuon calorimetry --neglected tropical deisease --praziquantel --Schistosoma mansoni --universal stress protein

Licence

• https://devspace.unizulu.ac.za/bitstreams/23bada10-14a2-4a2c-988d-ddd3d502b9c4/download