PAF-acetylhydrolases

Abstract

Platelet-activating factor acetylhydrolases (PAF-AHs, EC 3.1.1.47) constitute a unique subfamily of phospholipases A(2), specific for short acyl chains in the sn-2 position of the phospholipid. Their primary substrate is the platelet-activating factor, PAF, from which they cleave an acetyl moiety with concomitant release of lysoPAF. However, some acetylhydrolase will also hydrolyze other polar phospholipids with up to 6-carbons long acyl chains in the sn-2 position. PAF-acetylhydrolases are diverse enzymes, and the well-characterized isoforms are serine-dependent hydrolases, which do not require Ca(2+) for activity. Given the existence of two pools of PAF, intra- and extracellular, the acetylhydrolases can be divided into two subclasses: those found in the cytosol and enzymes secreted to blood plasma or other body fluids. Recent crystallographic studies shed new light on the complex structure-function relationships in PAF-AHs.

Biology of Platelet-activating Factor Acetylhydrolase (PAF-AH, Lipoprotein Associated Phospholipase A2)

“…The mechanism of ester hydrolysis suggests that the backbone amides of F274, immediately downstream of the catalytic serine (S273), and L153 form part of the oxyanion hole and stabilize tetrahedral intermediates generated during catalysis. In addition, residues 189-239 inserted at the carboxyl edge of the central β sheet have been proposed to define substrate specificity and lipoprotein binding [16]. Interestingly, we found that Y205 was required for binding of PAF-AH to LDL, and this residue is Fig.…”

“…Interestingly, we found that Y205 was required for binding of PAF-AH to LDL, and this residue is Fig. 2 Tertiary fold of PAF-AH based on previous models by Wei et al [15] and Derewenda and Ho [16] and modified to include newly discovered domains. Catalytic triad residues (S273, D296 and H351) and two residues that confer susceptibility to oxidation (Y305 and Y335) lie within loops proposed to connect helical and β sheet domains.…”

Secretory Phospholipases A₂ as Multivalent Mediators of Inflammatory and Allergic Disorders

“…The biochemistry and biological functions of the major cPLA 2 s (groups IV and VI) and acetyl hydrolases (groups VII and VIII) have been reviewed elsewhere [17, 18, 19, 20]. …”

Purification and Characterisation of a 31-kDa Chitinase from the Myzus Persicae Aphid: A Target for Hemiptera Biocontrol

“…Here, M. persicae chitinase matched with an acetylhydrolase found in A. pisum and platelet-activating factor acetylhydrolase (PAF hydrolase) from Drosophila, Aedes and Culex species. This kind of acetylhydrolase constitutes a subfamily of phospholipase specific for acyl chains [9]. The related phospholipids are key components of biological membranes and are the source of signaling molecules involved in many regulatory pathways associated with different physiological functions [8].…”

“…Consequently, M. persicae chitinase appeared to be different from other insect chitinases. Hypothesis on the change of functional constraints were developed to explain the divergences in insect chitinases [9]. The match between M. persicae chitinase, an endochitinase and a Concanavalin B suggests that it belongs to chitinases from family 18 such as previous insect chitinases studied so far that all have been shown to possess signature motifs characteristic of family 18 glycosyl hydrolases [2].…”