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

被引:30
作者
Bellinzoni, Marco [1 ,2 ]
Buroni, Silvia [3 ]
Schaeffer, Francis [1 ,2 ]
Riccardi, Giovanna [3 ]
De Rossi, Edda [3 ]
Alzari, Pedro M. [1 ,2 ]
机构
[1] Inst Pasteur, Unite Biochim Struct, F-75724 Paris 15, France
[2] CNRS URA2185, F-75724 Paris 15, France
[3] Univ Pavia, Dipartimento Genet & Microbiol, I-27100 Pavia, Italy
关键词
ANTIMICROBIAL RESISTANCE; PROTEIN; MECHANISMS; TRANSPORTERS; RECOGNITION; FLEXIBILITY; FAMILY;
D O I
10.1128/JB.00631-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:7531 / 7537
页数:7
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