6BRD

Crystal structure of rifampin monooxygenase from Streptomyces venezuelae, complexed with rifampin and FAD

Replaces:  5VQC

Summary for 6BRD

• Entry DOI: 10.2210/pdb6brd/pdb
• Related: 5VQB
• Descriptor: Rifampin monooxygenase, FLAVIN-ADENINE DINUCLEOTIDE, RIFAMPICIN, ... (6 entities in total)
• Functional Keywords: rifampin, rifamycin, antibiotic resistance, monooxygenase, oxidoreductase, fad, flavin adenine dinucleotide, structural genomics, csgid, center for structural genomics of infectious diseases, niaid, national institute of allergy and infectious disease
• Biological source: Streptomyces venezuelae (strain ATCC 10712 / CBS 650.69 / DSM 40230 / JCM 4526 / NBRC 13096 / PD 04745)
• Total number of polymer chains: 3
• Total formula weight: 162615.23

Authors

Cox, G.,Kelso, J.,Stogios, P.J.,Savchenko, A.,Anderson, W.F.,Wright, G.D.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2017-11-30, release date: 2017-12-13, Last modification date: 2023-10-04)

Primary citation

Koteva, K.,Cox, G.,Kelso, J.K.,Surette, M.D.,Zubyk, H.L.,Ejim, L.,Stogios, P.,Savchenko, A.,Sorensen, D.,Wright, G.D.
Rox, a Rifamycin Resistance Enzyme with an Unprecedented Mechanism of Action.
Cell Chem Biol, 25:403-412.e5, 2018

PubMed Abstract: Rifamycin monooxygenases (Rox) are present in a variety of environmental bacteria and are associated with decomposition of the clinically utilized antibiotic rifampin. Here we report the structure and function of a drug-inducible rox gene from Streptomyces venezuelae, which encodes a class A flavoprotein monooxygenase that inactivates a broad range of rifamycin antibiotics. Our findings describe a mechanism of rifamycin inactivation initiated by monooxygenation of the 2-position of the naphthyl group, which subsequently results in ring opening and linearization of the antibiotic. The result is an antibiotic that no longer adopts the basket-like structure essential for binding to the RNA exit tunnel of the target RpoB, thereby providing the molecular logic of resistance. This unique mechanism of enzymatic inactivation underpins the broad spectrum of rifamycin resistance mediated by Rox enzymes and presents a new antibiotic resistance mechanism not yet seen in microbial antibiotic detoxification.

PubMed: 29398560
DOI: 10.1016/j.chembiol.2018.01.009

Experimental method

X-RAY DIFFRACTION (3.32 Å)