engleski

Computational investigation of Helicobacter pylori purine nucleoside phosphorylase

Purine nucleoside phosphorylase (PNP) is an enzyme which participates in nucleoside degradation metabolism. Human and bacterial enzymes differ in primary amino acid sequence, oligomerisation in the native state (trimers and hexamers, respectively) and substrate specificity. The goal of this Thesis was to investigate structural and dynamic properties of Helicobacter pylori PNP (HpPNP) enzyme in apo form and in complexes with different ligands, the structure of which was recently solved using X-ray structure dete rmination, using computational methods. Ligand binding to the HpPNP enzyme active site was studied using molecular docking approach. Molecular dynamics simulations were used to investigate the influence of ligands on the HpPNP enzyme. Nine systems were simulated, up to 20 ns each. Seven of these systems contain ligands in HpPNP enzyme binding sites, while the remaining two contain no ligands. Non-covalent interactions between ligands and binding site amino acid residues were identified and analysed. Differences in conformations of the ligands bound and their influence on hydrogen bonds between hexamer subunits were observed. Large conformational changes of the HpPNP enzyme were detected using principal component analysis.

Helicobacter pylori, nucleoside metabolism, PNP, molecular docking, molecular dynamics

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