@article{db337c7bcd8448a3a8e449700b320e7a,
title = "Structural Evidence for Rifampicin Monooxygenase Inactivating Rifampicin by Cleaving Its Ansa-Bridge",
abstract = "Rifampicin monooxygenase (RIFMO) decreases the potency of rifampicin (RIF) by converting it to oxidative products. Further decomposition of RIF has been observed in bacteria producing RIFMO and contributes to RIFMO-mediated drug resistance. Here we report the first crystal structure of RIFMO in complex with the hydroxylated RIF product. The 2.10 {\AA} resolution structure reveals a breach of the ansa aliphatic chain of RIF between naphthoquinone C2 and amide N1. Our data suggest that RIFMO catalyzes the hydroxylation of RIF at the C2 atom followed by cleavage of the ansa linkage, which leads to inactivation of the antibiotic by preventing key contacts with the RNA polymerase target.",
author = "Liu, {Li Kai} and Yumin Dai and Heba Abdelwahab and Pablo Sobrado and Tanner, {John J.}",
note = "Funding Information: The authors thank Dr. Jay Nix for help with X-ray diffraction data collection at the Advanced Light Source and Dr. Wei G. Wycoff for providing comments on the NMR data. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract DE-AC02-05CH11231. Funding Information: *E-mail: psobrado@vt.edu. *E-mail: tannerjj@missouri.edu. ORCID Yumin Dai: 0000-0002-9228-3671 Pablo Sobrado: 0000-0003-1494-5382 John J. Tanner: 0000-0001-8314-113X Funding This work was supported by National Science Foundation Grants CHE-1506206 and MCB 1021384. Notes The authors declare no competing financial interest. Funding Information: This work was supported by National Science Foundation Grants CHE-1506206 and MCB 1021384. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract DE-AC02-05CH11231. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",
year = "2018",
month = apr,
day = "10",
doi = "10.1021/acs.biochem.8b00190",
language = "English (US)",
volume = "57",
pages = "2065--2068",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "14",
}