National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, China.
School of Life Science and Technology, Weifang Medical University, Weifang, China.
J Biol Chem. 2024 Jul;300(7):107466. doi: 10.1016/j.jbc.2024.107466. Epub 2024 Jun 12.
Glycosaminoglycan (GAG) lyases are often strictly substrate specific, and it is especially difficult to simultaneously degrade GAGs with different types of glycosidic bonds. Herein, we found a new class of GAG lyases (GAGases) from different bacteria. These GAGases belong to polysaccharide lyase 35 family and share quite low homology with the identified GAG lyases. The most surprising thing is that GAGases can not only degrade three types of GAGs: hyaluronan, chondroitin sulfate, and heparan sulfate but also even one of them can also degrade alginate. Further investigation of structural preferences revealed that GAGases selectively act on GAG domains composed of non/6-O-/N-sulfated hexosamines and d-glucoronic acids as well as on alginate domains composed of d-mannuronic acids. In addition, GAG lyases were once speculated to have evolved from alginate lyases, but no transitional enzymes have been found. The discovery of GAGases not only broadens the category of GAG lyases, provides new enzymatic tools for the structural and functional studies of GAGs with specific structures, but also provides candidates for the evolution of GAG lyases.
糖胺聚糖 (GAG) 裂解酶通常具有严格的底物特异性，同时降解具有不同糖苷键类型的 GAG 尤其困难。在此，我们从不同细菌中发现了一类新的 GAG 裂解酶 (GAGase)。这些 GAGase 属于多糖裂解酶 35 家族，与已鉴定的 GAG 裂解酶同源性较低。最令人惊讶的是，GAGase 不仅可以降解三种 GAG：透明质酸、硫酸软骨素和硫酸肝素，甚至还可以降解藻酸盐。对结构偏好的进一步研究表明，GAGase 选择性作用于由非/6-O-/N-硫酸己糖胺和 d-葡萄糖醛酸组成的 GAG 结构域，以及由 d-甘露糖醛酸组成的藻酸盐结构域。此外，GAG 裂解酶曾被推测是从藻酸盐裂解酶进化而来的，但尚未发现过渡酶。GAGase 的发现不仅拓宽了 GAG 裂解酶的类别，为具有特定结构的 GAG 的结构和功能研究提供了新的酶学工具，也为 GAG 裂解酶的进化提供了候选酶。
