Mechanism of metal ion activation of the diphtheria toxin repressor DtxR
Open accessAbstract
The diphtheria toxin repressor (DtxR) is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae . Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear. Calorimetric techniques have demonstrated that although binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 × 10 –7 , binding site 2 (primary) is a low-affinity binding site with a binding constant of 6.3 × 10 –4 . These two binding sites act in an independent fashion, and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A,C102D), reported here, and the previously reported DtxR(H79A) have allowed us to propose a mechanism of metal activation for DtxR.
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The mechanism of Fur regulation differs greatly from that of DtxR, in which a helix-to-coil transition and no DNA-induced conformational changes were observed.
“Overall, the mechanism of Fur regulation differs greatly from that of DtxR 25 , 29 , in which a helix-to-coil transition and no DNA-induced conformational changes were observed.”
From Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator (2015) · cites this paper as [29]
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- Authors
- D'Aquino, J. A., Tetenbaum-Novatt, J., White, A., Berkovitch, F., & Ringe, D.
- Affiliations
- Departments of Chemistry and Biochemistry and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454; and Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT 06877
- Boehringer Ingelheim (United States) (US)
- Corresponding author
- Ringe, Dagmar
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-12-13
- Volume
- 102
- Issue
- 51
- Pages
- 18408-18413
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1317899
- OpenAlex
- W1982757640
- Cited by
- 57
- References
- 38
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 6 · 2012: 6
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (GM68762, 0070319)
- School of Medicine, Boston University
- National Institutes of Health (0070319, 3p50gm068762-07s2, 1s10rr010493-01, GM68762)
- National Institute of General Medical Sciences (GM 68762, P50-GM068762)
- National Institute of Allergy and Infectious Diseases (AI-21628, R01AI021628)
- National Center for Research Resources (P41-RR-10888, S10 RR-10493, P41RR010888)
- Brookhaven National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Diphtheria, Corynebacterium, and Tetanus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- DtxR, metal ion activation, metal binding sites, transcriptional regulation, Corynebacterium diphtheriae, virulence, protein stability, DNA binding, nickel binding
- MeSH terms
- Bacterial Proteins, Binding Sites, Calorimetry, Corynebacterium diphtheriae, Cysteine, DNA-Binding Proteins, Histidine, Ligands, Nickel, Protein Denaturation, Temperature, Protein Folding, Crystallography, X-Ray
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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