ArticleThe Journal of biological chemistry2015
Structural Basis for the Regulation of the MmpL Transporters of Mycobacterium tuberculosis.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- The Biosynthetic Pathway of Mycolic Acids: Dual-Function Targets for Tuberculosis Therapeutics and Green Steroid Drugs Biomanufacturing.Pharmaceutics · 2025Review
- Multi-omics profiling reveals atypical sugar utilization and a key membrane composition regulator in Streptococcus pneumoniae.Nature communications · 2025Article
- Mycobacterium tuberculosis response to cholesterol is integrated with environmental pH and potassium levels via a lipid metabolism regulator.PLoS genetics · 2024Article
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- M. tuberculosis AlkX Encoded byMicrobiology spectrum · 2022Article
- The TbD1 Locus Mediates a Hypoxia-Induced Copper Response inFrontiers in microbiology · 2022Article
- Transcriptional regulation and drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics.Microorganisms · 2021Article
- Long-chain fatty acids alter transcription ofPeerJ · 2021Article
- COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking.Virus research · 2020Review
- The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system.The Biochemical journal · 2020Review
- MmpL Proteins in Physiology and Pathogenesis ofMicroorganisms · 2019Review
- Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound.PloS one · 2019Article
- Insights onFrontiers in microbiology · 2018Article
- Structural basis of operator sites recognition and effector binding in the TetR family transcription regulator FadR.Nucleic acids research · 2017Article
- Mycobacterial Metabolic Syndrome: LprG and Rv1410 Regulate Triacylglyceride Levels, Growth Rate and Virulence in Mycobacterium tuberculosis.PLoS pathogens · 2016Article
- Crystal structure of the Mycobacterium tuberculosis transcriptional regulator Rv0302.Protein science : a publication of the Protein Society · 2015Article
- Dodecanoic acid & palmitic acid disarms rifampicin resistance by putatively targeting mycobacterial efflux pump Rv1218c.The Indian journal of medical researchArticle
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the MmpL (mycobacterial membrane protein large) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complex regulatory network, including the TetR family transcriptional regulators Rv3249c and Rv1816. Here we report the crystal structures of these two regulators, revealing dimeric, two-domain molecules with architecture consistent with the TetR family of regulators. Buried extensively within the C-terminal regulatory domains of Rv3249c and Rv1816, we found fortuitous bound ligands, which were identified as palmitic acid (a fatty acid) and isopropyl laurate (a fatty acid ester), respectively. Our results suggest that fatty acids may be the natural ligands of these regulatory proteins. Using fluorescence polarization and electrophoretic mobility shift assays, we demonstrate the recognition of promoter and intragenic regions of multiple mmpL genes by these proteins. Binding of palmitic acid renders these regulators incapable of interacting with their respective operator DNAs, which will result in derepression of the corresponding mmpL genes. Taken together, these experiments provide new perspectives on the regulation of the MmpL family of transporters.
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