GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Yuan, Hua; Zhang, Jinru; Cai, Yujuan; Wu, Sheng; Yang, Kui; Chan, H.; Huang, Wei; Jin, Wen-Bing; Li, Yan; Yin, Yue; Igarashi, Yasuhiro; Yuan, Shuguang; Zhou, Jiahai; Tang, Gong-Li
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 8
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-01508-1
• Languages: English
• ISSNs: 2041-1723

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. GyrI-like proteins are small-molecule binding proteins that are widely distributed in prokaryotes and eukaryotes, with functions that are poorly characterized. Here, the authors identify GyrI-like proteins as cyclopropanoid cyclopropyl hydrolases that can confer resistance to cytotoxic cyclopropanoid compounds.