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 Å 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.
Recommended Citation
L. K. Liu et al., "Structural Evidence for Rifampicin Monooxygenase Inactivating Rifampicin by Cleaving its Ansa-Bridge," Biochemistry, vol. 57, no. 14, pp. 2065 - 2068, American Chemical Society, Apr 2018.
The definitive version is available at https://doi.org/10.1021/acs.biochem.8b00190
Department(s)
Chemistry
International Standard Serial Number (ISSN)
1520-4995; 0006-2960
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2024 American Chemical Society, All rights reserved.
Publication Date
10 Apr 2018
PubMed ID
29578336
Comments
National Science Foundation, Grant 1506206