Department of Chemistry, University of York, York, YO10 5DD, UK.
New England Biolabs, 240 County Road, Ipswich, MA, 01938, USA.
Nat Commun. 2019 Oct 23;10(1):4816. doi: 10.1038/s41467-019-12684-7.
Sialic acids are a family of related sugars that play essential roles in many biological events intimately linked to cellular recognition in both health and disease. Sialidases are therefore orchestrators of cellular biology and important therapeutic targets for viral infection. Here, we sought to define if uncharacterized sialidases would provide distinct paradigms in sialic acid biochemistry. We show that a recently discovered sialidase family, whose first member EnvSia156 was isolated from hot spring metagenomes, defines an unusual structural fold and active centre constellation, not previously described in sialidases. Consistent with an inverting mechanism, EnvSia156 reveals a His/Asp active center in which the His acts as a Brønsted acid and Asp as a Brønsted base in a single-displacement mechanism. A predominantly hydrophobic aglycone site facilitates accommodation of a variety of 2-linked sialosides; a versatility that offers the potential for glycan hydrolysis across a range of biological and technological platforms.
唾液酸是一类相关糖，在许多与健康和疾病中的细胞识别密切相关的生物学事件中发挥着重要作用。因此，唾液酸酶是细胞生物学的协调者，也是病毒感染的重要治疗靶点。在这里，我们试图确定是否未被表征的唾液酸酶会在唾液酸生物化学中提供独特的范例。我们表明，最近发现的唾液酸酶家族，其第一个成员 EnvSia156 是从温泉宏基因组中分离出来的，它定义了一个不寻常的结构折叠和活性中心组合，以前在唾液酸酶中没有描述过。与反转机制一致，EnvSia156 揭示了一个 His/Asp 活性中心，其中 His 作为布朗斯台德酸，Asp 作为布朗斯台德碱，在单取代机制中起作用。一个主要的疏水性糖苷配基位点有利于容纳各种 2-连接的唾液酸苷；这种多功能性为在一系列生物和技术平台上进行聚糖水解提供了潜力。
