Jones_2002_Faseb.J_16_441

Acetylcholinesterase (AChE) present on the surface of the trematode blood fluke Schistosoma has been implicated in the regulation of glucose scavenging from the host blood. Determination of the molecular structure and functional characteristics of this molecule is a crucial first step in understanding the novel function for AChE and in evaluating the potential of schistosome AChE as a target of new parasite control methods. We have determined the primary structure of acetylcholinesterase from Schistosoma haematobium. Immunolocalization studies confirmed that the enzyme was present on the parasite surface as well as in the muscle. The derived amino acid sequence possesses features common to acetylcholinesterases: the catalytic triad, six cysteines that form three intramolecular disulphide bonds, and aromatic residues lining the catalytic gorge. An unusual feature is that the fully processed native enzyme exists as a glycoinositol phospholipid (GPI)-anchored dimer, but the sequence of the C?terminus does not conform to the current consensus for GPI modification. The enzyme expressed in Xenopus oocytes showed conventional substrate specificity and sensitivity to established inhibitors of AChE, although it is relatively insensitive to the peripheral site inhibitor propidium iodide. Distinctions between host and parasite AChEs will allow the rational design of schistosome-specific drugs and vaccines.