Yuan, HuaZhang, JinruCai, YujuanWu, ShengYang, KuiChan, H. C. StephenHuang, WeiJin, Wen-BingLi, YanYin, YueIgarashi, YasuhiroYuan, ShuguangZhou, JiahaiTang, Gong-Li2017-12-042017-12-042017-12-04201710.1038/s41467-017-01508-1https://infoscience.epfl.ch/handle/20.500.14299/142563WOS:000415124000012Gyrl-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.text::journal::journal article::research article