Abstract
The desolvation of lipid molecules in a complex of the enzyme human synovial phospholipase A2 with a lipid membrane is investigated as a mechanism that enhances the overall activity of the enzyme. For this purpose the interaction of the enzyme phospholipase A2 with a dilauryl-phosphatityl-ethanolamin (DLPE) membrane monolayer surface has been studied by means of molecular dynamics simulations. Two enzyme-membrane complexes, a loose and a tight complex, are considered. For comparison, simulations are also carried out for the enzyme in aqueous solution. The conformation, dynamics, and energetics of the three systems are compared, and the interactions between the protein and lipid molecules are analyzed. Free energies of solvation are calculated for the lipid molecules in the enzyme-membrane interface. Along with the calculated dielectric susceptibility at this interface, the results show the desolvation of lipids in a tightly bound, but not in a loosely bound protein-membrane complex. The desolvated lipids are found to interact mainly with hydrophobic protein residues, including Leu-2, Val-3, Ala-18, Leu-19, Phe-24, Val-31, and Phe-70. The results also explain why the turnover rate of phospholipase A2 complexed to a membrane is enhanced after a critical amount of negatively charged reaction product is accumulated.
Published Version
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