期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-017-01508-1
关键词
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资金
- NSFC [21632007, 21502217, 21621002]
- STCSM [15ZR1449400, 15JC1400400]
- CAS [XDB20000000, QYZDJ-SSW-SLH037]
- State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University [MMLKF15-02]
Gyrl-like proteins are widely distributed in prokaryotes and eukaryotes, and recognized as small-molecule binding proteins. Here, we identify a subfamily of these proteins as cyclo-propanoid cyclopropyl hydrolases (CCHs) that can catalyze the hydrolysis of the potent DNA-alkylating agents yatakemycin (YTM) and CC-1065. Co-crystallography and molecular dynamics simulation analyses reveal that these CCHs share a conserved aromatic cage for the hydrolytic activity. Subsequent cytotoxic assays confirm that CCHs are able to protect cells against YTM. Therefore, our findings suggest that the evolutionarily conserved Gyrl-like proteins confer cellular protection against diverse xenobiotics via not only binding, but also catalysis.
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