Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo 192-0015, Japan; Research Fellow of Japan Society for the Promotion of Science (PD), Koujimachi, Chiyoda-ku, Tokyo 102-0083, Japan; Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo 192-0015, Japan.
Int J Biol Macromol. 2020 Dec 1;164:2895-2902. doi: 10.1016/j.ijbiomac.2020.08.173. Epub 2020 Aug 24.
Chitotriosidase (Chit1) and acidic mammalian chitinase (AMCase) have been attracting research interest due to their involvement in various pathological conditions such as Gaucher's disease and asthma, respectively. Both enzymes are highly expressed in mice, while the level of AMCase mRNA was low in human tissues. In addition, the chitinolytic activity of the recombinant human AMCase was significantly lower than that of the mouse counterpart. Here, we revealed a substantially higher chitinolytic and transglycosylation activity of human Chit1 against artificial and natural chitin substrates as compared to the mouse enzyme. We found that the substitution of leucine (L) by tryptophan (W) at position 218 markedly reduced both activities in human Chit1. Conversely, the L218W substitution in mouse Chit1 increased the activity of the enzyme. These results suggest that Chit1 may compensate for the low of AMCase activity in humans, while in mice, highly active AMCase may supplements low Chit1 activity.
几丁质酶 1（Chit1）和酸性哺乳动物几丁质酶（AMCase）由于分别参与戈谢病和哮喘等多种病理状况而引起了研究兴趣。这两种酶在小鼠中高度表达，而 AMCase mRNA 的水平在人体组织中较低。此外，重组人 AMCase 的几丁质酶活性明显低于其对应的鼠型酶。在这里，我们揭示了人 Chit1 对人工和天然几丁质底物的几丁质酶解和转糖苷活性明显高于鼠型酶。我们发现，位置 218 处的亮氨酸（L）被色氨酸（W）取代显着降低了人 Chit1 的这两种活性。相反，鼠 Chit1 中的 L218W 取代增加了酶的活性。这些结果表明，Chit1 可能补偿了人体中 AMCase 活性的降低，而在小鼠中，高活性的 AMCase 可能补充了低 Chit1 活性。
