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GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Gong-Li Tang, 2017. "GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection," Nature Communications, Nature, vol. 8(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01508-1
    DOI: 10.1038/s41467-017-01508-1
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    Cited by:

    1. Elwood A. Mullins & Jonathan Dorival & Gong-Li Tang & Dale L. Boger & Brandt F. Eichman, 2021. "Structural evolution of a DNA repair self-resistance mechanism targeting genotoxic secondary metabolites," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Wan-Hong Wen & Yue Zhang & Ying-Ying Zhang & Qian Yu & Chu-Chu Jiang & Man-Cheng Tang & Jin-Yue Pu & Lian Wu & Yi-Lei Zhao & Ting Shi & Jiahai Zhou & Gong-Li Tang, 2021. "Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics," Nature Communications, Nature, vol. 12(1), pages 1-11, December.

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