期刊
FRONTIERS IN MOLECULAR BIOSCIENCES
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.640356
关键词
kasugamycin; chitinase; glycoside hydrolase; inhibitor; target
资金
- National Natural Science Foundation of China [31871959, 31830076]
- Shenzhen Science and Technology Program [KQTD20180411143628272]
Kasugamycin, an aminoglycoside antibiotic, has been found to be a competitive inhibitor of glycoside hydrolase family 18 (GH18) chitinases in various organisms. It was discovered that the electrostatic interaction between kasugamycin and a conserved aspartate in GH18 chitinase is vital for its inhibitory activity. This research not only identifies new molecular targets of kasugamycin but also expands the understanding of GH inhibitor design by utilizing a scaffold unrelated to the substrate.
Kasugamycin, a well-known aminoglycoside antibiotic, has been used widely in agriculture and medicine to combat microbial pathogens by binding the ribosome to inhibit translation. Here, kasugamycin was discovered to be a competitive inhibitor of glycoside hydrolase family 18 (GH18) chitinases from three different organisms (bacterium, insect and human). Results from tryptophan fluorescence spectroscopy and molecular docking revealed that kasugamycin binds to the substrate-binding clefts in a similar mode as the substrate. An electrostatic interaction between the amino group of kasugamycin and the carboxyl group of a conserved aspartate in GH18 chitinase (one of the catalytic triad residues) was found to be vital for the inhibitory activity. This paper not only reports new molecular targets of kasugamycin, but also expands our thinking about GH inhibitor design by using a scaffold unrelated to the substrate.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据