Human phosphoglucose isomerase (hPGI) is important in glycolysis, catalyzing the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. It has been shown that distal amino acids, residues 11-13 Å away from the site of reaction, contribute to catalysis, such that single-site, conservative mutations at these residues result in significant loss of catalytic activity. The molecular dynamics simulations of wild-type PGI and of the Q388A variant were carried out to compare the electrostatic and hydrogen bonding network around the active site to determine the extent of contribution of structural changes. The side chain position shift of the catalytic residue H389 away from the substrate, by disrupting Q388 hydrogen bonds with N428, Q432, and Y341 with the A mutation, leads to the decrease in activity and stability. Together with electrostatics, dynamics contributes to an observed decrease in catalytic efficiency.

Structural, dynamic, and electrostatic influences on catalysis in wild type human phosphoglucose isomerase and the Q388A variant

254th National Meeting (2017)

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