In silico studies to understand structure/function of exopolyphosphatase active site from Escherichia coli

BOETSCH, C; LISA, AT; BEASSONI, PR

Buenos Aires

Congreso; International Society of Computational Biology-Latin America - A2B2C Bioinformatics; 2016

nternational Society for Computational Biology

Escherichia coli exopolyphosphatase (ecPpx) belongs to ASKHA superfamily, it is a dimer that hydrolyzes polyphosphate (polyP) in a proccesive way to yield PolyP(n-1)and orthophosphate (Pi). Putative catalytic residues and the Mg2+binding pocket were suggested. ecPpx does not recognize ATP or ADP, probably because the presence of clashes between the sugar and nitrogenous base with ecPpx redidues. However, tetra-polyphosphate and penta-polyphosphate inhibited ecPpx regulating it activity and demonstrate the clashes may be avoided.In this work, we perform docking assays, multiple sequence alignment and structural alignments to analyze polyP and nucleotide binding to active site. We also compared this enzyme with its orthologue in Pseudomonas aeruginosa (paPpx), witch, additionally, has transferase activity from polyP to ADP.Docking assays suggested the binding to active site is guide by the polyP portion of nucleotides as the nucleoside fraction is highly variable. We also proposed a binding model for ADP and polyP in paPpx.The findings made in this study may set the basis for rational drug design for infection treatments against the polyphosphatases explicity, without affecting human ATP binding proteins.Supported by CONICET and SeCyT-UNRC