Characterization of a platelet-activating factor acetylhydrolase secreted by the nematode parasite Nippostrongylus brasiliensis.
Nippostrongylus brasiliensis, a small nematode parasite of the gastrointestinal tract of rodents, secretes an enzyme that cleaves the proinflammatory molecule platelet-activating factor to its inactive lyso-form. The enzyme activity of Ca(2+)-dependent and does not exhibit interfacial activation. It does not require the addition of reducing agents for maximal activity, and is not inhibited by thiol-active reagents. Sensitivity of inhibitors suggests the involvement of serine and histidine residues in the enzyme activity. As described for other platelet-activating factor acetylhydrolases, it cannot cleave, nor is it inhibited by, long-chain diacyl phospholipids that are typical substrates for phospholipases A2. The purified enzyme was resolved by SDS/PAGE as a heterodimer composed of two protein subunits with apparent molecular masses of 38 and 25 kDa. The properties of the nematode enzyme thus differ from those described for the mammalian enzymes, but are more closely related to those of an acetylhydrolase than a phospholipase.
Grigg
M E
ME
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, UK.
Gounaris
K
K
Selkirk
M E
ME
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D009559:Nippostrongylus / Q000201:enzymology*; D017830:Octoxynol / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
D002413:Cations, Divalent; D010972:Platelet Activating Factor; D017830:Octoxynol; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase