GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29133784.
- Also identified by DOI 10.1038/s41467-017-01508-1 and PMC identifier 5684135.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Alkylating Agents
- Bacterial Physiological Phenomena
- Biocatalysis
- Drug Resistance, Bacterial
- Hydrolases