Lipoprotein‐associated phospholipase A2 structure and function (774.3)

Lipoprotein‐associated phospholipase A 2 (LpPLA 2 ) or plasma platelet‐activating factor acetylhydrolase (pPAFAH) is a serine hydrolase that acts on platelet‐activating factor (PAF) and oxidized phospholipids. The enzyme has a classic α/β hydrolase fold and predicted membrane binding regions. Plasma PAFAH binds readily to both high density lipoproteins (HDL) and low density lipoproteins (LDL) and is believed to play a pro‐atherosclerotic role. The purpose of this study is to further elucidate the structure and function of LpPLA 2 through the use of specific inhibitors. It was necessary to develop and refine an expression method in E. coli to produce high quantities of protein of high purity for a truncated form of LpPLA 2 . Successful expression and purification of this LpPLA 2 construct have been achieved and initial trials of crystallization were positive. The next step in this study is to obtain the crystal structure of LpPLA 2 along with its selective inhibitors. Grant Funding Source : Supported by NIHNHLBI grant #RO1HL084366