Structural and functional studies of Purine nucleoside phosphorylase isoform 2, Methylthioadenosine phosphorylase and participants enzymes of GTP production from purine salvage pathway from Schistosoma mansoni.
The parasitic diseases, are the biggest cause of the death on progress countries, therefore it don't receive any attention by pharmaceutical industry for development of therapeutics processes. The schistosomiasis affects approximately 207 million people worldwide and 6 million on Brazil. The parasite Schistosoma mansoni does not possess "de novo" pathway for purine bases biosynthesis and depends entirely on salvage pathways for its purine requirement. Thus this pathway can be identified as a potential target to be explored. The Inosine monophosphate dehydrogenase (IMPDH), GMP-syntetase (GMPS), Guanylate kinase (GK), Nucleoside diphosphate kinase (NDPK), Purine nucleoside phosphorylase isoform 2 (PNP2) and Methylthioadenosine phosphorylase (MTAP) enzymes are involved in this pathway. The IMPDH is responsible for converting inosine monophosphate into xhantine monophosphate, the GMPS for converting xhantine monophosphate into guanosine monophosphate, the NDPK for converting nucleotides diphosphate into correspondent nucleotides triphosphate, the PNP2 for reversible phosphorolysis of purines nucleosides and the MTAP for converting adenosine into adenine. The objectives this study are clone, express and purify the IMPDH, GMPS, GK e PNP2 enzymes for structural and functional determination, beyond accurate investigation of the catalytic mechanisms from MTAP enzyme. This project is inserted on larger project on progress, which purpose is to obtain the tridimensional structure and catalytic constants of the all enzymes from the purine salvation pathway from Schistosoma mansoni.
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