ArticleBiochemistry2012
Solution structure of Mycobacterium tuberculosis NmtR in the apo state: insights into Ni(II)-mediated allostery.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- The role of transcriptional regulators in metal ion homeostasis ofFrontiers in cellular and infection microbiology · 2024Review
- Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation inbioRxiv : the preprint server for biology · 2023Article
- Coordination Properties of the Zinc Domains of BigR4 and SmtB Proteins in Nickel Systems─Designation of Key Donors.Inorganic chemistry · 2022Article
- Structural and mechanistic basis for redox sensing by the cyanobacterial transcription regulator RexT.Communications biology · 2022Article
- Nickel Metalloregulators and Chaperones.Inorganics · 2019Article
- Negative regulation of daptomycin production by DepR2, an ArsR-family transcriptional factor.Journal of industrial microbiology & biotechnology · 2017Article
- Solution NMR Studies of Mycobacterium tuberculosis Proteins for Antibiotic Target Discovery.Molecules (Basel, Switzerland) · 2017Review
- Metallochaperones and metalloregulation in bacteria.Essays in biochemistry · 2017Review
- Cadmium(II) inhibition of human uracil-DNA glycosylase by catalytic water supplantation.Scientific reports · 2016Article
- Crystallization and preliminary X-ray analysis of Rv1674c from Mycobacterium tuberculosis.Acta crystallographica. Section F, Structural biology communications · 2015Article
- Role of substrate dynamics in protein prenylation reactions.Accounts of chemical research · 2015Review
- Transcription factor-based biosensors enlightened by the analyte.Frontiers in microbiology · 2015Review
- Characterizing solution surface loop conformational flexibility of the GM2 activator protein.The journal of physical chemistry. B · 2014Article
- Insights into Protein Allostery in the CsoR/RcnR Family of Transcriptional Repressors.Chemistry letters · 2014Article
- Organization and regulation of the arsenite oxidase operon of the moderately acidophilic and facultative chemoautotrophic Thiomonas arsenitoxydans.Extremophiles : life under extreme conditions · 2013Article
- Physical characterization of the manganese-sensing pneumococcal surface antigen repressor from Streptococcus pneumoniae.Biochemistry · 2013Article
- Rational Design of Particle Mesh Ewald Compatible Lennard-Jones Parameters for +2 Metal Cations in Explicit Solvent.Journal of chemical theory and computation · 2013Article
- Solution NMR refinement of a metal ion bound protein using metal ion inclusive restrained molecular dynamics methods.Journal of biomolecular NMR · 2013Article
- Allosteric inhibition of a zinc-sensing transcriptional repressor: insights into the arsenic repressor (ArsR) family.Journal of molecular biology · 2013Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis is an obligate human respiratory pathogen that encodes approximately 10 arsenic repressor (ArsR) family regulatory proteins that allow the organism to respond to a wide range of changes in its immediate microenvironment. How individual ArsR repressors have evolved to respond to selective stimuli is of intrinsic interest. The Ni(II)/Co(II)-specific repressor NmtR and related actinomycete nickel sensors harbor a conserved N-terminal α-NH(2)-Gly2-His3-Gly4 sequence. Here, we present the solution structure of homodimeric apo-NmtR and show that the core of the molecule adopts a typical winged-helix ArsR repressor (α1-α2-α3-αR-β1-β2-α5) "open conformation" that is similar to that of the related zinc sensor Staphylococcus aureus CzrA, but harboring long, flexible N-terminal (residues 2-16) and C-terminal (residues 109-120) extensions. Binding of Ni(II) to the regulatory sites induces strong paramagnetic broadening of the α5 helical region and the extreme N-terminal tail to residue 10. Ratiometric pulse chase amidination mass spectrometry reveals that the rate of amidination of the α-amino group of Gly2 is strongly attenuated in the Ni(II) complex relative to the apo state and noncognate Zn(II) complex. Ni(II) binding also induces dynamic disorder on the microsecond to millisecond time scale of key DNA interacting regions that likely contributes to the negative regulation of DNA binding by Ni(II). Molecular dynamics simulations and quantum chemical calculations reveal that NmtR readily accommodates a distal Ni(II) hexacoordination model involving the α-amine and His3 of the N-terminal region and α5 residues Asp91', His93', His104, and His107, which collectively define a new metal sensing site configuration in ArsR family regulators.
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