CRYSTAL-STRUCTURE OF VIBRIO-CHOLERAE NEURAMINIDASE REVEALS DUAL LECTIN-LIKE DOMAINS IN ADDITION TO THE CATALYTIC DOMAIN
CRYSTAL-STRUCTURE OF VIBRIO-CHOLERAE NEURAMINIDASE REVEALS DUAL LECTIN-LIKE DOMAINS IN ADDITION TO THE CATALYTIC DOMAIN
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DOI：
10.1016/s0969-2126(00)00053-8
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发表时间：
1994-06-15
期刊：
影响因子：
5.7
通讯作者：
TAYLOR, G
中科院分区：
文献类型：
--
作者：
CRENNELL, S;GARMAN, E;TAYLOR, G
背景：霍乱弧菌神经氨酸酶是粘蛋白酶复合物的一部分，其可能通过降解胃肠道的粘蛋白层在发病机制中发挥作用。神经氨酸酶一直是广泛抑制剂研究的目标，它通过将高级神经节苷脂加工成霍乱毒素受体 G(M1)，在细菌的病理学中发挥着微妙的作用。 结果：我们在此报告了分辨率为 2.3 埃的霍乱弧菌神经氨酸酶的 X 射线晶体结构。 83 kDa 的酶折叠成三个不同的结构域。中心催化结构域具有典型的神经氨酸酶β-螺旋桨折叠，两侧是两个具有相同豆科植物凝集素样拓扑但没有常见金属结合环的结构域。该活性位点与其他病毒和细菌神经氨酸酶具有许多共同特征，但独特的是，它具有一个必需的 Ca2+ 离子，在结构中起着至关重要的作用。结论：小肠环境需要霍乱弧菌分泌多种粘附素，已知其神经氨酸酶可以与细胞表面结合并保持活性。意想不到的凝集素样结构域可能介导这种附着。这些细菌凝集素折叠代表了不断增长的凝集素超家族的其他成员。
Background: Vibrio cholerae neuraminidase is part of a mucinase complex which may function in pathogenesis by degrading the mucin layer of the gastrointestinal tract. The neuraminidase, which has been the target of extensive inhibitor studies, plays a subtle role in the pathology of the bacterium, by processing higher order gangliosides to G(M1), the receptor for cholera toxin.Results: We report here the X-ray crystal structure of V. cholerae neuraminidase at 2.3 Angstrom resolution. The 83 kDa enzyme folds into three distinct domains. The central catalytic domain has the canonical neuraminidase beta-propeller fold, and is flanked by two domains which possess identical legume lectin-like topologies but without the usual metal-binding loops. The active site has many features in common with other viral and bacterial neuraminidases but, uniquely, has an essential Ca2+ ion which plays a crucial structural role.Conclusions: The environment of the small intestine requires V. cholerae to secrete several adhesins, and it is known that its neuraminidase can bind to cell surfaces, and remain active. The unexpected lectin-like domains possibly mediate this attachment. These bacterial lectin folds represent additional members of a growing lectin superfamily.