ArticleBiochemistry2014
DNA consensus sequence motif for binding response regulator PhoP, a virulence regulator of Mycobacterium tuberculosis.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- In Host Mutational Adaptation of Mycobacterium Tuberculosis Complex Strains During Tuberculosis Infection.The Journal of infectious diseases · 2026Pooled it
- Transcriptional control of asparagine utilization regulates mycobacterial pH-driven adaptation at the host-pathogen crossroads.The Journal of biological chemistry · 2026Article
- Structural insights into transcription regulation of the global OmpR/PhoB family regulator PhoP from Mycobacterium tuberculosis.Nature communications · 2025Article
- Article
- Clinically relevant mutations in the PhoR sensor kinase of host-adaptedMicrobiology spectrum · 2023Article
- Substrate DNA Promoting Binding ofMicroorganisms · 2023Article
- TheFrontiers in microbiology · 2023Article
- The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.Molecular biomedicine · 2022Review
- Convergence of two global regulators to coordinate expression of essential virulence determinants ofeLife · 2022Article
- Deletion of the Response Regulator PhoP Accelerates the Formation of Aerial Mycelium and Spores inFrontiers in microbiology · 2022Article
- Tools to map target genes of bacterial two-component system response regulators.Environmental microbiology reports · 2020Review
- Metabolic Switching ofJournal of bacteriology · 2020Article
- Biofilm architecture: An emerging synthetic biology target.Synthetic and systems biotechnology · 2020Review
- Calcium Regulation of Bacterial Virulence.Advances in experimental medicine and biology · 2020Review
- Metabolic intermediate acetyl phosphate modulates bacterial virulence via acetylation.Emerging microbes & infections · 2019Article
- PhoPR Positively RegulatesJournal of bacteriology · 2018Article
- The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism.Journal of molecular biology · 2018Article
- Deciphering the protein-DNA code of bacterial winged helix-turn-helix transcription factors.Quantitative biology (Beijing, China) · 2018Article
- EspR-dependent ESAT-6 Protein Secretion of Mycobacterium tuberculosis Requires the Presence of Virulence Regulator PhoP.The Journal of biological chemistry · 2016Article
- Structural basis of DNA sequence recognition by the response regulator PhoP in Mycobacterium tuberculosis.Scientific reports · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Tuberculosis has reemerged as a serious threat to human health because of the increasing prevalence of drug-resistant strains and synergetic infection with HIV, prompting an urgent need for new and more efficient treatments. The PhoP-PhoR two-component system of Mycobacterium tuberculosis plays an important role in the virulence of the pathogen and thus represents a potential drug target. To study the mechanism of gene transcription regulation by response regulator PhoP, we identified a high-affinity DNA sequence for PhoP binding using systematic evolution of ligands by exponential enrichment. The sequence contains a direct repeat of two 7 bp motifs separated by a 4 bp spacer, TCACAGC(N4)TCACAGC. The specificity of the direct-repeat sequence for PhoP binding was confirmed by isothermal titration calorimetry and electrophoretic mobility shift assays. PhoP binds to the direct repeat as a dimer in a highly cooperative manner. We found many genes previously identified to be regulated by PhoP that contain the direct-repeat motif in their promoter sequences. Synthetic DNA fragments at the putative promoter-binding sites bind PhoP with variable affinity, which is related to the number of mismatches in the 7 bp motifs, the positions of the mismatches, and the spacer and flanking sequences. Phosphorylation of PhoP increases the affinity but does not change the specificity of DNA binding. Overall, our results confirm the direct-repeat sequence as the consensus motif for PhoP binding and thus pave the way for identification of PhoP directly regulated genes in different mycobacterial genomes.
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Registered trials
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.