molecular model of plasma paf acetylhydrolase-lipoprotein association insights from the structure等离子体的分子模型拥堵acetylhydrolase-lipoprotein协会结构的见解.pdfVIP

Pharmaceuticals 2010, 3, 541-557; doi:10.3390/ph3030541 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure Prabhavathi Srinivasan and Brian J. Bahnson * Department of Chemistry Biochemistry, University of Delaware, Newark, DE 19716, USA * Author to whom correspondence should be addressed; E-Mail: bahnson@; Tel.: +1-302-831-0786; Fax: +1-302-831-6335. Received: 9 January 2010; in revised form: 7 February 2010 / Accepted: 5 March 2010 / Published: 8 March 2010 Abstract: Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called lipoprotein-associated phospholipase A (Lp-PLA ), is a group VIIA PLA enzyme that 2 2 2 catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL hav