ArticleNucleic acids research2014
Structural mechanism of transcription regulation of the Staphylococcus aureus multidrug efflux operon mepRA by the MarR family repressor MepR.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 44 citations in OpenAlex.
- The MarR family regulator RmaH underlies the trade-off between acid sensitivity and antibiotic tolerance inJournal of bacteriology · 2026Article
- CdmR, a MarR family protein fromBiochemistry and biophysics reports · 2025Article
- Identification of genetic mutations conferring tedizolid resistance in MRSA mutants.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Small-angle x-ray and neutron scattering of MexR and its complex with DNA supports a conformational selection binding model.Biophysical journal · 2023Article
- Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition.Antibiotics (Basel, Switzerland) · 2021Review
- Heme controls the structural rearrangement of its sensor protein mediating the hemolytic bacterial survival.Communications biology · 2021Article
- The evolution of MarR family transcription factors as counter-silencers in regulatory networks.Current opinion in microbiology · 2020Review
- MarR family proteins are important regulators of clinically relevant antibiotic resistance.Protein science : a publication of the Protein Society · 2020Review
- Genetic compensation byCell cycle (Georgetown, Tex.) · 2019Article
- Specificity of protein-DNA interactions in hypersaline environment: structural studies on complexes of Halobacterium salinarum oxidative stress-dependent protein hsRosR.Nucleic acids research · 2019Article
- Chemoproteomics of an Indole-Based Quinone Epoxide Identifies Druggable Vulnerabilities in Vancomycin-ResistantJournal of medicinal chemistry · 2019Article
- Plasticity in oligomerization, operator architecture, and DNA binding in the mode of action of a bacterial BThe Journal of biological chemistry · 2018Article
- Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator.eLife · 2018Article
- Structural basis of transcriptional regulation by CouR, a repressor of coumarate catabolism, inThe Journal of biological chemistry · 2018Article
- Resistance in In Vitro Selected Tigecycline-Resistant Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Is Driven by Mutations in mepR and mepA Genes.Microbial drug resistance (Larchmont, N.Y.) · 2018Article
- Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis.Scientific reports · 2017Article
- Structural characterization of the DNA-binding mechanism underlying the copper(II)-sensing MarR transcriptional regulator.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Article
- The activity of CouR, a MarR family transcriptional regulator, is modulated through a novel molecular mechanism.Nucleic acids research · 2016Article
- Purification, crystallization and X-ray crystallographic studies of a Bacillus cereus MepR-like transcription factor, BC0657.Acta crystallographica. Section F, Structural biology communications · 2015Article
- Mutations within the mepA operator affect binding of the MepR regulatory protein and its induction by MepA substrates in Staphylococcus aureus.Journal of bacteriology · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multidrug efflux pump MepA is a major contributor to multidrug resistance in Staphylococcus aureus. MepR, a member of the multiple antibiotic resistance regulator (MarR) family, represses mepA and its own gene. Here, we report the structure of a MepR-mepR operator complex. Structural comparison of DNA-bound MepR with 'induced' apoMepR reveals the large conformational changes needed to allow the DNA-binding winged helix-turn-helix motifs to interact with the consecutive major and minor grooves of the GTTAG signature sequence. Intriguingly, MepR makes no hydrogen bonds to major groove nucleobases. Rather, recognition-helix residues Thr60, Gly61, Pro62 and Thr63 make sequence-specifying van der Waals contacts with the TTAG bases. Removing these contacts dramatically affects MepR-DNA binding activity. The wings insert into the flanking minor grooves, whereby residue Arg87, buttressed by Asp85, interacts with the O2 of T4 and O4' ribosyl oxygens of A23 and T4. Mutating Asp85 and Arg87, both conserved throughout the MarR family, markedly affects MepR repressor activity. The His14':Arg59 and Arg10':His35:Phe108 interaction networks stabilize the DNA-binding conformation of MepR thereby contributing significantly to its high affinity binding. A structure-guided model of the MepR-mepA operator complex suggests that MepR dimers do not interact directly and cooperative binding is likely achieved by DNA-mediated allosteric effects.
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