Modulator of drug activity B from Escherichia coli: crystal structure of a prokaryotic homologue of DT-diaphorase

Journal of Molecular Biology
Melanie A Adams, Zongchao Jia

Abstract

Modulator of drug activity B (MdaB) is a putative member of the DT-diaphorase family of NAD(P)H:oxidoreductases that afford cellular protection against quinonoid compounds. While there have been extensive investigations of mammalian homologues, putative prokaryotic members of this enzyme family have received little attention. The three-dimensional crystal structure of apo-MdaB reported herein exhibits significant structural similarity to a number of flavoproteins, including the mammalian DT-diaphorases. We have shown by mass spectrometry that the endogenously associated cofactor is flavin adenine dinucleotide and we present here the structure of MdaB in complex with this compound. Growth of Escherichia coli carrying null mutations in the genes encoding MdaB or quinol monooxygenase, the gene for which shares the mdaB promoter, were not affected by the presence of menadione. However, over-expression of recombinant quinol monooxygenase conferred a state of resistance against both tetracycline and adriamycin. This work suggests that the redox cycle formed by these proteins protects E. coli from the toxic effects of polyketide compounds rather than the oxidative stress of menadione alone.

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Citations

Jul 17, 2008·Applied Microbiology and Biotechnology·Paul SchweigerUwe Deppenmeier
Sep 6, 2013·Applied Microbiology and Biotechnology·Jiachuan PanDacheng Ren
Aug 2, 2007·Journal of Structural and Functional Genomics·Allan MatteMiroslaw Cygler
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Aug 2, 2006·Molecular Microbiology·Ge WangRobert J Maier
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Oct 4, 2015·The Biochemical Journal·Elsie M WilliamsDavid F Ackerley
Dec 2, 2015·The Biochemical Journal·Vincenzo CrescenteAli Ryan
Apr 5, 2014·Acta Crystallographica. Section D, Biological Crystallography·Zixi WangXiao-Dong Su
Sep 19, 2018·IUCrJ·Bart van BeusekomAnastassis Perrakis
Jan 14, 2009·Archives of Biochemistry and Biophysics·Vojtech SedlácekIgor Kucera

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