@article{8d681b3011f44cbcaa2b934eef5f4063,
title = "Structural and functional analyses of the echinomycin resistance conferring protein Ecm16 from Streptomyces lasalocidi",
abstract = "Echinomycin is a natural product DNA bisintercalator antibiotic. The echinomycin biosynthetic gene cluster in Streptomyces lasalocidi includes a gene encoding the self-resistance protein Ecm16. Here, we present the 2.0 {\AA} resolution crystal structure of Ecm16 bound to adenosine diphosphate. The structure of Ecm16 closely resembles that of UvrA, the DNA damage sensor component of the prokaryotic nucleotide excision repair system, but Ecm16 lacks the UvrB-binding domain and its associated zinc-binding module found in UvrA. Mutagenesis study revealed that the insertion domain of Ecm16 is required for DNA binding. Furthermore, the specific amino acid sequence of the insertion domain allows Ecm16 to distinguish echinomycin-bound DNA from normal DNA and link substrate binding to ATP hydrolysis activity. Expression of ecm16 in the heterologous host Brevibacillus choshinensis conferred resistance against echinomycin and other quinomycin antibiotics, including thiocoraline, quinaldopeptin, and sandramycin. Our study provides new insight into how the producers of DNA bisintercalator antibiotics fend off the toxic compounds that they produce.",
author = "Priyanka Gade and Amanda Erlandson and Anwar Ullah and Xi Chen and Mathews, {Irimpan I.} and Mera, {Paola E.} and Kim, {Chu Young}",
note = "Funding Information: We thank Dr. Marcin Nowotny for providing the expression plasmid for Thermotoga maritima UvrA. X-ray diffraction data were collected at the Advanced Photon Source and at the Stanford Synchrotron Radiation Lightsource. Advanced Photon Source, a DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). This work was supported by the University of Texas System STARs Award (C.-Y.K.), Projects of International Cooperation in Shaanxi Province of China 2023-GHYB-08 (X.C.), Open Project Program of the State Key Tumor Biology Laboratory CBSKL2022KF13 (X.C.). Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = dec,
doi = "10.1038/s41598-023-34437-9",
language = "English (US)",
volume = "13",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}