Cremona M L, Pollevick G D, Frasch A C, Campetella O
Instituto de Investigaciones Bioquímicas Luis F. Leloir Fundación Campomar, Buenos Aires, Argentina.
Cell Mol Biol (Noisy-le-grand). 1996 Jul;42(5):697-702.
Neuraminidases have been implicated in various processes involving the interaction of pathogens and their receptor cells. Trypanosoma cruzi, the agent of Chagas disease, has an unusual neuraminidase, able to transfer bound alpha(2-3)sialic acid to a suitable acceptor rather than to water: the trans-sialidase (TcTS). This enzyme is encoded by a family of several homologous genes, some of them rendering inactive the products. We have shown that enzymatically active proteins have Tyr in position 342, whereas inactive TcTS contain a His342. We have now mutated this Tyr residue to Phe or Thr. Both mutant proteins resulted in enzymatically inactive products. Chimeras expressing parts of Salmonella typhimurium neuraminidase (NANH) and TcTS were constructed. Only the construct containing the complete NANH molecule fused to the last 272 residues of TcTS had neuraminidase activity. However this construct did not present TcTS activity. This finding suggests that other residues present in the homology region are required for TcTS activity.
神经氨酸酶参与了病原体与其受体细胞相互作用的各种过程。恰加斯病的病原体克氏锥虫具有一种不同寻常的神经氨酸酶,它能够将结合的α(2-3)唾液酸转移到合适的受体上,而不是转移到水中:即转唾液酸酶(TcTS)。这种酶由几个同源基因家族编码,其中一些基因使产物失去活性。我们已经表明,具有酶活性的蛋白质在342位含有酪氨酸,而无活性的TcTS含有组氨酸342。我们现在已将该酪氨酸残基突变为苯丙氨酸或苏氨酸。两种突变蛋白都产生了无酶活性的产物。构建了表达鼠伤寒沙门氏菌神经氨酸酶(NANH)和TcTS部分片段的嵌合体。只有包含与TcTS最后272个残基融合的完整NANH分子的构建体具有神经氨酸酶活性。然而,该构建体不具有TcTS活性。这一发现表明,同源区域中存在的其他残基是TcTS活性所必需 的。