ArticleThe Journal of biological chemistry2016
The Molecular Basis of TnrA Control by Glutamine Synthetase in Bacillus subtilis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Mechanisms and biotechnological applications of transcription factors.Synthetic and systems biotechnology · 2023Review
- The Functionality of IbpA fromInternational journal of molecular sciences · 2023Article
- Understanding and application of Bacillus nitrogen regulation: A synthetic biology perspective.Journal of advanced research · 2023Review
- Alanine synthesized by alanine dehydrogenase enables ammonium-tolerant nitrogen fixation inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria.Nature communications · 2022Article
- Analysis of Protein-DNA Interactions Using Surface Plasmon Resonance and a ReDCaT Chip.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Complete Genome Sequence of Lactobacillus hilgardii LMG 7934, Carrying the Gene Encoding for the Novel PII-Like Protein PotN.Current microbiology · 2020Article
- N- and C-terminal regions of the small heat shock protein IbpA fromRSC advances · 2020Article
- Interaction of N-acetyl-l-glutamate kinase with the PII signal transducer in the non-photosynthetic alga Polytomella parva: Co-evolution towards a hetero-oligomeric enzyme.The FEBS journal · 2020Article
- Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5International journal of molecular sciences · 2019Article
- Positive and negative regulation of transferred nif genes mediated by indigenous GlnR in Gram-positive Paenibacillus polymyxa.PLoS genetics · 2018Article
- Novel antibiofilm chemotherapies target nitrogen from glutamate and glutamine.Scientific reports · 2018Article
- Revisiting the in vivo GlnR-binding sites at the genome scale in Bacillus subtilis.BMC research notes · 2017Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TnrA is a master regulator of nitrogen assimilation in Bacillus subtilis. This study focuses on the mechanism of how glutamine synthetase (GS) inhibits TnrA function in response to key metabolites ATP, AMP, glutamine, and glutamate. We suggest a model of two mutually exclusive GS conformations governing the interaction with TnrA. In the ATP-bound state (A-state), GS is catalytically active but unable to interact with TnrA. This conformation was stabilized by phosphorylated L-methionine sulfoximine (MSX), fixing the enzyme in the transition state. When occupied by glutamine (or its analogue MSX), GS resides in a conformation that has high affinity for TnrA (Q-state). The A- and Q-state are mutually exclusive, and in agreement, ATP and glutamine bind to GS in a competitive manner. At elevated concentrations of glutamine, ATP is no longer able to bind GS and to bring it into the A-state. AMP efficiently competes with ATP and prevents formation of the A-state, thereby favoring GS-TnrA interaction. Surface plasmon resonance analysis shows that TnrA bound to a positively regulated promoter fragment binds GS in the Q-state, whereas it rapidly dissociates from a negatively regulated promoter fragment. These data imply that GS controls TnrA activity at positively controlled promoters by shielding the transcription factor in the DNA-bound state. According to size exclusion and multiangle light scattering analysis, the dodecameric GS can bind three TnrA dimers. The highly interdependent ligand binding properties of GS reveal this enzyme as a sophisticated sensor of the nitrogen and energy state of the cell to control the activity of DNA-bound TnrA.
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