6C7S

Structure of Rifampicin Monooxygenase with Product Bound

6C7S の概要

• エントリーDOI: 10.2210/pdb6c7s/pdb
• 関連するPDBエントリー: 5KOW 5KOX
• 分子名称: 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)
• 機能のキーワード: rifampicin, oxidoreductase
• 由来する生物種: Nocardia farcinica (strain IFM 10152)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53692.33

構造登録者

Liu, L.-K.,Tanner, J.J. (登録日: 2018-01-23, 公開日: 2018-04-18, 最終更新日: 2023-10-04)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.1 Å)