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GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection.

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.

SUBMITTER: Yuan H

PROVIDER: S-EPMC5684135 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection.

Yuan Hua H Zhang Jinru J Cai Yujuan Y Wu Sheng S Yang Kui K Chan H C Stephen HCS Huang Wei W Jin Wen-Bing WB Li Yan Y Yin Yue Y Igarashi Yasuhiro Y Yuan Shuguang S Zhou Jiahai J Tang Gong-Li GL

Nature communications 20171114 1

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 confir ...[more]

PMID: 29133784

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