Jones Andrew K, Bentley Geoffrey N, Oliveros Parra William G, Agnew Alison
The School of Biology, University of Leeds, Leeds, West Yorkshire, UK, LS2 9JT.
FASEB J. 2002 Mar;16(3):441-3. doi: 10.1096/fj.01-0683fje. Epub 2002 Jan 30.
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.
寄生血吸虫表面存在的乙酰胆碱酯酶（AChE）与从宿主血液中清除葡萄糖的调节有关。确定该分子的分子结构和功能特性是理解AChE新功能以及评估血吸虫AChE作为新的寄生虫控制方法靶点潜力的关键第一步。我们已经确定了埃及血吸虫乙酰胆碱酯酶的一级结构。免疫定位研究证实该酶存在于寄生虫表面以及肌肉中。推导的氨基酸序列具有乙酰胆碱酯酶的共同特征：催化三联体、形成三个分子内二硫键的六个半胱氨酸以及催化峡谷内衬的芳香族残基。一个不寻常的特征是，完全加工的天然酶以糖基磷脂酰肌醇（GPI）锚定的二聚体形式存在，但C末端序列不符合目前GPI修饰的共识。在非洲爪蟾卵母细胞中表达的该酶表现出常规的底物特异性和对已确立的AChE抑制剂的敏感性，尽管它对周边位点抑制剂碘化丙啶相对不敏感。宿主和寄生虫AChE之间的差异将有助于合理设计针对血吸虫的药物和疫苗。
