National Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, China.
State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
Int J Mol Sci. 2023 Apr 6;24(7):6830. doi: 10.3390/ijms24076830.
Sialidases are increasingly used in the production of sialyloligosaccharides, a significant component of human milk oligosaccharides. Elucidating the catalytic mechanism of sialidases is critical for the rational design of better biocatalysts, thereby facilitating the industrial production of sialyloligosaccharides. Through comparative all-atom molecular dynamics simulations, we investigated the structural dynamics of sialidases in Glycoside Hydrolase family 33 (GH33). Interestingly, several sialidases displayed significant conformational transition and formed a new cleft in the simulations. The new cleft was adjacent to the innate active site of the enzyme, which serves to accommodate the glycosyl acceptor. Furthermore, the residues involved in the specific interactions with the substrate were evolutionarily conserved in the whole GH33 family, highlighting their key roles in the catalysis of GH33 sialidases. Our results enriched the catalytic mechanism of GH33 sialidases, with potential implications in the rational design of sialidases.
唾液酸酶在唾液酸寡糖的生产中被广泛应用，而唾液酸寡糖是人类乳寡糖的重要组成部分。阐明唾液酸酶的催化机制对于理性设计更好的生物催化剂至关重要，从而促进唾液酸寡糖的工业生产。通过比较全原子分子动力学模拟，我们研究了糖苷水解酶家族 33（GH33）中唾液酸酶的结构动力学。有趣的是，一些唾液酸酶在模拟中显示出明显的构象转变，并形成了一个新的裂缝。这个新的裂缝与酶的固有活性位点相邻，用于容纳糖基受体。此外，与底物特异性相互作用相关的残基在整个 GH33 家族中是保守的，这突出了它们在 GH33 唾液酸酶催化中的关键作用。我们的研究结果丰富了 GH33 唾液酸酶的催化机制，对于理性设计唾液酸酶具有潜在的意义。
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