Structural Plasticity and Distinct Drug-Binding Modes of LfrR, a Mycobacterial Efflux Pump Regulator - Archive ouverte HAL Access content directly
Journal Articles Journal of Bacteriology Year : 2009

Structural Plasticity and Distinct Drug-Binding Modes of LfrR, a Mycobacterial Efflux Pump Regulator

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Abstract

The TetR-like transcriptional repressor LfrR controls the expression of the gene encoding the Mycobacterium smegmatis efflux pump LfrA, which actively extrudes fluoroquinolones, cationic dyes, and anthracyclines from the cell and promotes intrinsic antibiotic resistance. The crystal structure of the apoprotein form of the repressor reveals a structurally asymmetric homodimer exhibiting local unfolding and a blocked drug-binding site, emphasizing the significant conformational plasticity of the protein necessary for DNA and multidrug recognition. Crystallographic and calorimetric studies of LfrR-drug complexes further confirm the intrinsic flexibility of the homodimer, which provides a dynamic mechanism to broaden multidrug binding specificity and may be a general property of transcriptional repressors regulating microbial efflux pump expression.

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pasteur-03137957 , version 1 (10-02-2021)

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Marco Bellinzoni, Silvia Buroni, Francis Schaeffer, Giovanna Riccardi, Edda de Rossi, et al.. Structural Plasticity and Distinct Drug-Binding Modes of LfrR, a Mycobacterial Efflux Pump Regulator. Journal of Bacteriology, 2009, 191 (24), pp.7531-7537. ⟨10.1128/JB.00631-09⟩. ⟨pasteur-03137957⟩

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