GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection

Hua Yuan, Jinru Zhang, Yujuan Cai, Sheng Wu, Kui Yang, H. C. Stephen Chan, Wei Huang, Wen-Bing Jin, Yan Li, Yue Yin, Yasuhiro Igarashi, Shuguang Yuan (), Jiahai Zhou () and Gong-Li Tang ()
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Hua Yuan: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Jinru Zhang: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Yujuan Cai: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Sheng Wu: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Kui Yang: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
H. C. Stephen Chan: University of Bradford
Wei Huang: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Wen-Bing Jin: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Yan Li: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Yue Yin: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Yasuhiro Igarashi: Toyama Prefectural University
Shuguang Yuan: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Jiahai Zhou: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Gong-Li Tang: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract GyrI-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 cyclopropanoid 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 GyrI-like proteins confer cellular protection against diverse xenobiotics via not only binding, but also catalysis.

Date: 2017
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DOI: 10.1038/s41467-017-01508-1

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