期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 15, 期 5, 页码 1155-1163出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.200801512
关键词
enzymes; inhibitors; natural products; phospholipases; protein interactions
资金
- University of Salerno
- MIUR (Rome)
- Regione Campania (Italy) through POR funds
We report in analysis of the mechanism of human group IIA secretory phospholipase A, (sPLA(2)-IIA) inhibition by the natural anti-inflammatory sesterterpene petrosaspongiolide M (PM). The amphiphilic PM, a gamma-hydroxybutenolide marine terpenoid, selectively reacts with the sPLA(2)-IIA Lys67 residue, located near the enzyme-membrane interfacial binding surface, and covalently modifies the enzyme through imine formation. Furthermore, PM is able to target the active site of sPLA(2)-IIA through several van der Waals/electrostatic complementarities. The two events cannot co-occur on a single PLA(2) molecule, so they may contribute separately to enzyme inhibiton. A more intriguing hypothesis suggests a double interaction of PM with two enzyme molecules, one of them covalently modified and the other contacting the inhibitor through its active site. We have explored the occurrence of this unusual binding mode leading to PM-induced PLA(2) supramolecular complexes. These insights could suggest new PLA(2)-inhibition-based therapeutic strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据