Gonzalez_2015_Enzymes_38_95

The structure of plasma PAF-AH was solved to a resolution of 1.5A using X-ray crystallography. The enzyme has a classic alpha/beta serine hydrolase fold containing a catalytic triad of Ser273, Asp296, and His351. A hydrophobic patch of the enzyme involving two alpha-helices (114-126 and 362-369) and neighboring residues have been shown to be essential for lipoprotein particle binding by mutagenesis and mass spectrometry hydrogen/deuterium exchange experiments. An interface-bound model of the enzyme positions the active site above the hydrophobic-hydrophilic interface and is consistent with the known substrate specificity of the enzyme. Several ligand-bound structures of plasma PAF-AH have been solved with organophosphorus compounds and modeled with competitive inhibitors of high affinity and selectivity. This chapter presents an overview of the structure of plasma PAF-AH, molecular details of its functional role, and the interaction of the enzyme with lipoprotein particles.