J. Biochem, 1993, Vol. 114, No. 2 210
© 1993 Japanese Biochemical Society
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Molecular Dynamics Simulation of 1,2-Dilauroy1-L-Phosphatidylethanolamine Binding to Phospholipase A2: An Attempt to Explain the Selective Hydrolysis of Substrate Fatty Acid Ester at Position 2
*Osaka University of Pharmaceutical Sciences 2-10-65 Kawai, Matsubara, Osaka 580
**National Chemical Laboratory for Industry Tsukuba, Ibaraki 305
***Research Center of Taisho Pharmaceutical Co., Ltd. 1-403 Yoshino-cho, Ohmiya, Saitama 330
1To whom correspondence should be addressed.
To improve our understanding of why phospholipase A2 (PLA2) specifically catalyzes the hydrolysis of the fatty acid ester bond at position 2, not at position 1, of 1,2-diacyl-3-sn-phosphoglycerides, the binding of each fatty acid chain of 1,2-dilauroyl-L-phosphatidyl-ethanolamine (DLPE), a natural substrate, to bovine pancreas PLA2 was examined by molecular dynamics (MD) simulations. Two different binding modes were considered, i.e., the respective hydrocarbon chains of 1- and 2-lauroyl fatty acid esters were located at the PLA2 binding sites usually observed in the complex crystals (Form A2) and at the reverse sites (Form Al). Although the total energies of both forms fluctuated within nearly the same range during the 80 ps MD simulations, the binding mode of DLPE to the PLA2 catalytic site through the coordination to Ca2+ was much more advantageous in Form A2 than that in Form Al; significant deviation of the Ca2+ position from its starting structure was observed in the MD simulation of Form Al. The result suggests the importance of Ca2+ in the selective recognition and catalytic function of PLA2 toward the 2-positioned fatty acid ester of phosphoglyceride substrates.