6C7S

Structure of Rifampicin Monooxygenase with Product Bound

Summary for 6C7S

• Entry DOI: 10.2210/pdb6c7s/pdb
• Related: 5KOW 5KOX
• Descriptor: Putative rifampin monooxygenase, FLAVIN-ADENINE DINUCLEOTIDE, (1E,3S,4R,5S,6R,7R,8R,9S,10S,11E,13E)-15-amino-1-{[(2S)-5,7-dihydroxy-2,4-dimethyl-8-{(E)-[(4-methylpiperazin-1-yl)imino]methyl}-1,6,9-trioxo-1,2,6,9-tetrahydronaphtho[2,1-b]furan-2-yl]oxy}-7,9-dihydroxy-3-methoxy-4,6,8,10,14-pentamethyl-15-oxopentadeca-1,11,13-trien-5-yl acetate, ... (6 entities in total)
• Functional Keywords: rifampicin, oxidoreductase
• Biological source: Nocardia farcinica (strain IFM 10152)
• Total number of polymer chains: 1
• Total formula weight: 53692.33

Authors

Liu, L.-K.,Tanner, J.J. (deposition date: 2018-01-23, release date: 2018-04-18, Last modification date: 2023-10-04)

Primary citation

Liu, L.K.,Dai, Y.,Abdelwahab, H.,Sobrado, P.,Tanner, J.J.
Structural Evidence for Rifampicin Monooxygenase Inactivating Rifampicin by Cleaving Its Ansa-Bridge.
Biochemistry, 57:2065-2068, 2018

PubMed 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.

PubMed: 29578336
DOI: 10.1021/acs.biochem.8b00190

Experimental method

X-RAY DIFFRACTION (2.1 Å)