ArticleThe Journal of biological chemistry2014
Crystal structure of the transcriptional regulator Rv0678 of Mycobacterium tuberculosis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Opportunities and limitations of genomics for diagnosing bedaquiline-resistant tuberculosis: a systematic review and individual isolate meta-analysis.The Lancet. Microbe · 2024Pooled it
- Structure, assembly, and mechanism of the MmpL family of transporters.Microbiology and molecular biology reviews : MMBR · 2026Review
- Convolutional neural networks quantify antibiotic resistance in Mycobacterium tuberculosis with diagnostic grade accuracy and predict treatment response.Nature communications · 2026Article
- Article
- The AcasR-FadD9 regulatory axis modulates iron homeostasis and susceptibility to the anti-mycobacterial compound ACA.Frontiers in tuberculosis · 2026Article
- Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters.Science advances · 2025Article
- Structure and assembly of the MmpL5/MmpS5 efflux transporter from Mycobacterium tuberculosis.Nature communications · 2025Article
- High Prevalence of atpE Mutations in Bedaquiline-Resistant Mycobacterium tuberculosis Isolates, Russia.Emerging infectious diseases · 2025Article
- Mycobactin and clofazimine activity are negatively correlated in mycobacteria.Frontiers in microbiology · 2025Article
- Frameshift mutations in theAntimicrobial agents and chemotherapy · 2024Article
- Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024Review
- Cigarette Smoking as a Risk Factor for Tuberculosis in Adults: Epidemiology and Aspects of Disease Pathogenesis.Pathogens (Basel, Switzerland) · 2024Review
- TheMicrobiology spectrum · 2024Article
- Polypharmacology-Driven Discovery and Design of Highly Selective, Dual and Multitargeting Inhibitors ofCurrent drug targets · 2024Review
- Bedaquiline- and clofazimine- selected Mycobacterium tuberculosis mutants: further insights on resistance driven largely by Rv0678.Scientific reports · 2023Article
- Site-directed mutagenesis of Mycobacterium tuberculosis and functional validation to investigate potential bedaquiline resistance-causing mutations.Scientific reports · 2023Article
- Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis.The Lancet. Microbe · 2023Article
- Genome-Wide Study of Drug ResistantMicroorganisms · 2022Article
- Hit Compounds and Associated Targets in IntracellularMolecules (Basel, Switzerland) · 2022Article
- Immunobiology of tubercle bacilli and prospects of immunomodulatory drugs to tackle tuberculosis (TB) and other non-tubercular mycobacterial infections.Immunobiology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Recent work demonstrates that the MmpL (mycobacterial membrane protein large) transporters are dedicated to the export of mycobacterial lipids for cell wall biosynthesis. An MmpL transporter frequently works with an accessory protein, belonging to the MmpS (mycobacterial membrane protein small) family, to transport these key virulence factors. One such efflux system in Mycobacterium tuberculosis is the MmpS5-MmpL5 transporter. The expression of MmpS5-MmpL5 is controlled by the MarR-like transcriptional regulator Rv0678, whose open reading frame is located downstream of the mmpS5-mmpL5 operon. To elucidate the structural basis of Rv0678 regulation, we have determined the crystal structure of this regulator, to 1.64 Å resolution, revealing a dimeric two-domain molecule with an architecture similar to members of the MarR family of transcriptional regulators. Rv0678 is distinct from other MarR regulators in that its DNA-binding and dimerization domains are clustered together. These two domains seemingly cooperate to bind an inducing ligand that we identified as 2-stearoylglycerol, which is a fatty acid glycerol ester. The structure also suggests that the conformational change leading to substrate-mediated derepression is primarily caused by a rigid body rotational motion of the entire DNA-binding domain of the regulator toward the dimerization domain. This movement results in a conformational state that is incompatible with DNA binding. We demonstrate using electrophoretic mobility shift assays that Rv0678 binds to the mmpS5-mmpL5, mmpS4-mmpL4, and the mmpS2-mmpL2 promoters. Binding by Rv0678 was reversed upon the addition of the ligand. These findings provide new insight into the mechanisms of gene regulation in the MarR family of regulators.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.