Secretory Phospholipase A2 Activity toward Diverse Substrates

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• 作者：Jesper J. Madsen ; Lars Linderoth ; Arun K. Subramanian ; Thomas L. Andresen ; Gu虉nther H. Peters
• 刊名：Journal of Physical Chemistry B
• 出版年：2011
• 出版时间：June 2, 2011
• 年：2011
• 卷：115
• 期：21
• 页码：6853-6861
• 全文大小：1057K
• 年卷期：v.115,no.21(June 2, 2011)
• ISSN：1520-5207

文摘

We have studied secretory phospholipase A₂-IIA (sPLA₂) activity toward different phospholipid analogues by performing biophysical characterizations and molecular dynamics simulations. The phospholipids were natural substrates, triple alkyl phospholipids, a prodrug anticancer etherlipid, and an inverted ester. The latter were included to study head group鈥揺nzyme interactions. Our simulation results show that the lipids are optimally placed into the binding cleft and that water molecules can freely reach the active site through a well-defined pathway; both are indicative that these substrates are efficiently hydrolyzed, which is in good agreement with our experimental data. The phospholipid analogue with three alkyl side chains forms aggregates of different shapes with no well-defined sizes due to its cone-shape structure. Phosphatidylglycerol and phosphatidylcholine head groups interact with specific charged residues, but relatively large fluctuations are observed, suggesting that these interactions are not necessarily important for stabilizing substrate binding to the enzyme.