Comparative functional analysis between human and mouse chitotriosidase: Substitution at amino acid 218 modulates the chitinolytic and transglycosylation activity
Comparative functional analysis between human and mouse chitotriosidase: Substitution at amino acid 218 modulates the chitinolytic and transglycosylation activity
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DOI：
10.1016/j.ijbiomac.2020.08.173
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发表时间：
2020-12-01
影响因子：
8.2
通讯作者：
Oyama, Fumitaka
中科院分区：
文献类型：
--
作者：
Kimura, Masahiro;Watanabe, Takashi;Oyama, Fumitaka
几丁三糖苷酶 (Chit1) 和酸性哺乳动物几丁质酶 (AMCase) 因其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 水平在人体组织中较低。此外，重组人AMCase的几丁质分解活性显着低于小鼠对应物。在这里，我们发现与小鼠酶相比，人 Chit1 对人工和天然几丁质底物具有显着更高的几丁质分解和转糖基活性。我们发现，在 218 位用色氨酸 (W) 替换亮氨酸 (L) 显着降低了人 Chit1 中的这两种活性。相反，小鼠 Chit1 中的 L218W 取代增加了该酶的活性。这些结果表明，Chit1 可以弥补人类 AMCase 活性的低下，而在小鼠中，高活性 AMCase 可以补充 Chit1 的低活性。 (C) 2020 作者。由 Elsevier B.V. 出版
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. (C) 2020 The Authors. Published by Elsevier B.V.