ArticleNucleic acids research2012
Structural and functional analysis of the transcriptional regulator Rv3066 of Mycobacterium tuberculosis.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
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- Transcriptional regulation and drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- Transcriptional Response ofFrontiers in microbiology · 2021Article
- Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions.PloS one · 2020Article
- The prominent alteration in transcriptome and metabolome of Mycobacterium bovis BCG str. Tokyo 172 induced by vitamin BBMC microbiology · 2019Article
- Defining informative priors for ensemble modeling in systems biology.Nature protocols · 2018Article
- Molecular mechanism of the synergistic activity of ethambutol and isoniazid againstThe Journal of biological chemistry · 2018Article
- Avoiding Antibiotic Inactivation in Mycobacterium tuberculosis by Rv3406 through Strategic Nucleoside Modification.ACS infectious diseases · 2018Article
- Insights onFrontiers in microbiology · 2018Article
- Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy.BMC medicine · 2016Article
- Genome-Wide De Novo Prediction of Cis-Regulatory Binding Sites in Mycobacterium tuberculosis H37Rv.PloS one · 2016Article
- Crystal structure of the Mycobacterium tuberculosis transcriptional regulator Rv0302.Protein science : a publication of the Protein Society · 2015Article
- Structural Basis for the Regulation of the MmpL Transporters of Mycobacterium tuberculosis.The Journal of biological chemistry · 2015Article
- A GntR family transcription factor positively regulates mycobacterial isoniazid resistance by controlling the expression of a putative permease.BMC microbiology · 2015Article
- InbR, a TetR family regulator, binds with isoniazid and influences multidrug resistance in Mycobacterium bovis BCG.Scientific reports · 2015Article
- Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions.BMC genomics · 2015Article
- Comparing Mycobacterium tuberculosis genomes using genome topology networks.BMC genomics · 2015Article
- Structural and functional characterization of a ketosteroid transcriptional regulator of Mycobacterium tuberculosis.The Journal of biological chemistry · 2015Article
- Crystal structure of the transcriptional regulator Rv0678 of Mycobacterium tuberculosis.The Journal of biological chemistry · 2014Article
- Energy metabolism and drug efflux in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2014Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The Mmr multidrug efflux pump recognizes and actively extrudes a broad range of antimicrobial agents, and promotes the intrinsic resistance to these antimicrobials in Mycobacterium tuberculosis. The expression of Mmr is controlled by the TetR-like transcriptional regulator Rv3066, whose open reading frame is located downstream of the mmr operon. To understand the structural basis of Rv3066 regulation, we have determined the crystal structures of Rv3066, both in the absence and presence of bound ethidium, revealing an asymmetric homodimeric two-domain molecule with an entirely helical architecture. The structures underscore the flexibility and plasticity of the regulator essential for multidrug recognition. Comparison of the apo-Rv3066 and Rv3066-ethidium crystal structures suggests that the conformational changes leading to drug-mediated derepression is primarily due to a rigid body rotational motion within the dimer interface of the regulator. The Rv3066 regulator creates a multidrug-binding pocket, which contains five aromatic residues. The bound ethidium is found buried within the multidrug-binding site, where extensive aromatic stacking interactions seemingly govern the binding. In vitro studies reveal that the dimeric Rv3066 regulator binds to a 14-bp palindromic inverted repeat sequence in the nanomolar range. These findings provide new insight into the mechanisms of ligand binding and Rv3066 regulation.
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