Li Dan-Dan, Wang Jin-Lan, Liu Ya, Li Yue-Zhong, Zhang Zheng
State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266237, China.
National Administration of Health Data, Jinan 250002, China.
Comput Struct Biotechnol J. 2021 Nov 2;19:5931-5942. doi: 10.1016/j.csbj.2021.10.039. eCollection 2021.
Glycoside hydrolases (GHs) are greatly diverse in sequences and functions, but systematic studies of GH relationships based on structural information are lacking. Here, we report that GHs have multiple evolutionary origins and are structurally derived from 27 homologous superfamilies and 16 folds, but GHs are highly biased to distribute in a few superfamilies and folds. Six of these superfamilies are widely encoded by archaea, bacteria, and eukaryotes, indicating that they may be the most ancient in origin. Most superfamilies vary in enzyme function, and some, such as the superfamilies of (β/α)-barrel and (α/α)-barrel structures, exhibit extreme functional diversity; this is highly positively correlated with sequence diversity. More than one-third of glycosidase activities show a phenomenon of convergent evolution, especially the degradation functions of GHs on polysaccharides. The GHs of most superfamilies have relatively narrow environmental distributions, normally with the highest abundance in host-associated environments and a distribution preference for moderate low-temperature and acidic environments. Overall, our expanded analysis facilitates an understanding of complex GH sequence-structure-function relationships and may guide our screening and engineering of GHs.
糖苷水解酶（GHs）在序列和功能上具有极大的多样性，但基于结构信息对GH关系进行的系统研究却很缺乏。在此，我们报告称，GHs有多个进化起源，在结构上源自27个同源超家族和16种折叠方式，但GHs在分布上高度偏向于少数超家族和折叠方式。其中六个超家族在古菌、细菌和真核生物中广泛编码，这表明它们可能起源最为古老。大多数超家族的酶功能各不相同，有些超家族，如（β/α）-桶状和（α/α）-桶状结构的超家族，表现出极端的功能多样性；这与序列多样性高度正相关。超过三分之一的糖苷酶活性呈现趋同进化现象，尤其是GHs对多糖的降解功能。大多数超家族的GHs具有相对狭窄的环境分布，通常在宿主相关环境中丰度最高，并且倾向于分布在中等低温和酸性环境中。总体而言，我们扩展后的分析有助于理解复杂的GH序列-结构-功能关系，并可能指导我们对GHs的筛选和工程改造。
