Gyrl-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection

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.


Published in:
Nature Communications, 8, 1485
Year:
2017
Publisher:
London, Nature Publishing Group
ISSN:
2041-1723
Laboratories:




 Record created 2017-12-04, last modified 2018-03-17


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