GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yuan, Hua, Zhang, Jinru, Cai, Yujuan, Wu, Sheng, Yang, Kui, Chan, H. C. Stephen, Huang, Wei, Jin, Wen-Bing, Li, Yan, Yin, Yue, Igarashi, Yasuhiro, Yuan, Shuguang, Zhou, Jiahai, Tang, Gong-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684135/
https://www.ncbi.nlm.nih.gov/pubmed/29133784
http://dx.doi.org/10.1038/s41467-017-01508-1
Descripción
Sumario: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.

Ejemplares similares