ArticleBiochemistry2013
Physical characterization of the manganese-sensing pneumococcal surface antigen repressor from Streptococcus pneumoniae.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes.Microbiology spectrum · 2023Article
- Mechanistic insights into the nickel-dependent allosteric response of the Helicobacter pylori NikR transcription factor.The Journal of biological chemistry · 2023Article
- The oxidative stress response ofFrontiers in microbiology · 2023Review
- MntP and YiiP Contribute to Manganese Efflux in Salmonella enterica Serovar Typhimurium under Conditions of Manganese Overload and Nitrosative Stress.Microbiology spectrum · 2022Article
- Cellular Mn/Zn Ratio Influences Phosphoglucomutase Activity and Capsule Production in Streptococcus pneumoniae D39.Journal of bacteriology · 2021Article
- Molecular Evolution of Transition Metal Bioavailability at the Host-Pathogen Interface.Trends in microbiology · 2021Review
- Staphylococcus aureus lacking a functional MntABC manganese import system has increased resistance to copper.Molecular microbiology · 2021Article
- Allosteric control of metal-responsive transcriptional regulators in bacteria.The Journal of biological chemistry · 2020Review
- Metal sensing and regulation of adaptive responses to manganese limitation by MtsR is critical for group A streptococcus virulence.Nucleic acids research · 2019Article
- Dietary zinc and the control of Streptococcus pneumoniae infection.PLoS pathogens · 2019Article
- A Mn-sensing riboswitch activates expression of a Mn2+/Ca2+ ATPase transporter in Streptococcus.Nucleic acids research · 2019Article
- Metallochaperones and metalloregulation in bacteria.Essays in biochemistry · 2017Review
- The zinc efflux activator SczA protects Streptococcus pneumoniae serotype 2 D39 from intracellular zinc toxicity.Molecular microbiology · 2017Article
- Perturbation of manganese metabolism disrupts cell division in Streptococcus pneumoniae.Molecular microbiology · 2017Article
- Molecular Insights into Hydrogen Peroxide-sensing Mechanism of the Metalloregulator MntR in Controlling Bacterial Resistance to Oxidative Stresses.The Journal of biological chemistry · 2017Article
- Stress Physiology of Lactic Acid Bacteria.Microbiology and molecular biology reviews : MMBR · 2016Review
- Functional Determinants of Metal Ion Transport and Selectivity in Paralogous Cation Diffusion Facilitator Transporters CzcD and MntE in Streptococcus pneumoniae.Journal of bacteriology · 2016Article
- Interactions of the Metalloregulatory Protein SloR from Streptococcus mutans with Its Metal Ion Effectors and DNA Binding Site.Journal of bacteriology · 2015Article
- Generating a Metal-responsive Transcriptional Regulator to Test What Confers Metal Sensing in Cells.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Transition metals, including manganese, are required for the proper virulence and persistence of many pathogenic bacteria. In Streptococcus pneumoniae (Spn), manganese homeostasis is controlled by a high-affinity Mn(II) uptake complex, PsaBCA, and a constitutively expressed efflux transporter, MntE. psaBCA expression is transcriptionally regulated by the DtxR/MntR family metalloregulatory protein pneumococcal surface antigen repressor (PsaR) in Spn. Here, we present a comprehensive analysis of the metal and DNA binding properties of PsaR. PsaR is a homodimer in the absence and presence of metals and binds two manganese or zinc atoms per protomer (four per dimer) in two pairs of structurally distinct sites, termed site 1 and site 2. Site 1 is likely filled with Zn(II) in vivo (K(Zn1) ≥ 10¹³ M⁻¹; K(Mn1) ≈ 10⁸ M⁻¹). The Zn(II)-site 1 complex adopts a pentacoordinate geometry as determined by X-ray absorption spectroscopy containing a single cysteine and appears to be analogous to the Cd(II) site observed in Streptococcus gordonii ScaR. Site 1 is necessary but not sufficient for full positive allosteric activation of DNA operator binding by metals as measured by ΔGc, the allosteric coupling free energy, because site 1 mutants show an intermediate ΔGc. Site 2 is the primary regulatory site and governs specificity for Mn(II) over Zn(II) in PsaR, where ΔGc(Zn,Mn) >> ΔGc(Zn,Zn) despite the fact that Zn(II) binds site 2 with an affinity 40-fold higher than that of Mn(II); i.e., K(Zn2) > K(Mn2). Mutational studies reveal that Asp7 in site 2 is a critical ligand for Mn(II)-dependent allosteric activation of DNA binding. These findings are discussed in the context of other well-studied DtxR/MntR Mn(II)/Fe(II) metallorepressors.
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Registered trials
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