ArticleProceedings of the National Academy of Sciences of the United States of America2012
ESR spectroscopy identifies inhibitory Cu2+ sites in a DNA-modifying enzyme to reveal determinants of catalytic specificity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 76 citations in OpenAlex.
- Caught in the Middle: A Rigid DNA Label That Provides an Incisive Picture of DNA Conformational Flexibility in Protein-DNA Complexes.Journal of the American Chemical Society · 2025Article
- A supramolecular metalloenzyme possessing robust oxidase-mimetic catalytic function.Nature communications · 2023Article
- Copper chelating cyclic peptidomimetic inhibits Aβ fibrillogenesis.RSC medicinal chemistry · 2022Article
- Methodology for rigorous modeling of protein conformational changes by Rosetta using DEER distance restraints.PLoS computational biology · 2021Article
- Pulsed EPR Dipolar Spectroscopy on Spin Pairs with one Highly Anisotropic Spin Center: The Low-Spin FeChemistry (Weinheim an der Bergstrasse, Germany) · 2019Article
- A trade-off for covalent and intercalation binding modes: a case study for Copper (II) ions and singly modified DNA nucleoside.Scientific reports · 2019Article
- Site-Specific Incorporation of a CuThe journal of physical chemistry. B · 2018Article
- Nucleic Acid-Dependent Conformational Changes in CRISPR-Cas9 Revealed by Site-Directed Spin Labeling.Cell biochemistry and biophysics · 2017Article
- Interaction between Prion Protein's Copper-Bound Octarepeat Domain and a Charged C-Terminal Pocket Suggests a Mechanism for N-Terminal Regulation.Structure (London, England : 1993) · 2016Article
- Distance measurements between paramagnetic ligands bound to parallel stranded guanine quadruplexes.Physical chemistry chemical physics : PCCP · 2016Article
- DEER Sensitivity between Iron Centers and Nitroxides in Heme-Containing Proteins Improves Dramatically Using Broadband, High-Field EPR.The journal of physical chemistry letters · 2016Article
- The double-histidine Cu²⁺-binding motif: a highly rigid, site-specific spin probe for electron spin resonance distance measurements.Angewandte Chemie (International ed. in English) · 2015Article
- Genetic Incorporation of the Unnatural Amino Acid p-Acetyl Phenylalanine into Proteins for Site-Directed Spin Labeling.Methods in enzymology · 2015Article
- Protein structural studies by paramagnetic solid-state NMR spectroscopy aided by a compact cyclen-type Cu(II) binding tag.Journal of biomolecular NMR · 2015Article
- Insights into copper coordination in the EcoRI-DNA complex by ESR spectroscopy.Molecular physics · 2014Article
- New developments in spin labels for pulsed dipolar EPR.Molecules (Basel, Switzerland) · 2014Review
- Copper-based pulsed dipolar ESR spectroscopy as a probe of protein conformation linked to disease states.Biophysical journal · 2014Article
- Thermodynamic and structural basis for relaxation of specificity in protein-DNA recognition.Journal of molecular biology · 2014Article
- mtsslSuite:Molecular physics · 2013Article
- Technological advances in site-directed spin labeling of proteins.Current opinion in structural biology · 2013Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The relationship between DNA sequence recognition and catalytic specificity in a DNA-modifying enzyme was explored using paramagnetic Cu(2+) ions as probes for ESR spectroscopic and biochemical studies. Electron spin echo envelope modulation spectroscopy establishes that Cu(2+) coordinates to histidine residues in the EcoRI endonuclease homodimer bound to its specific DNA recognition site. The coordinated His residues were identified by a unique use of Cu(2+)-ion based long-range distance constraints. Double electron-electron resonance data yield Cu(2+)-Cu(2+) and Cu(2+)-nitroxide distances that are uniquely consistent with one Cu(2+) bound to His114 in each subunit. Isothermal titration calorimetry confirms that two Cu(2+) ions bind per complex. Unexpectedly, Mg(2+)-catalyzed DNA cleavage by EcoRI is profoundly inhibited by Cu(2+) binding at these hitherto unknown sites, 13 Å away from the Mg(2+) positions in the catalytic centers. Molecular dynamics simulations suggest a model for inhibition of catalysis, whereby the Cu(2+) ions alter critical protein-DNA interactions and water molecule positions in the catalytic sites. In the absence of Cu(2+), the Mg(2+)-dependence of EcoRI catalysis shows positive cooperativity, which would enhance EcoRI inactivation of foreign DNA by irreparable double-strand cuts, in preference to readily repaired single-strand nicks. Nonlinear Poisson-Boltzmann calculations suggest that this cooperativity arises because the binding of Mg(2+) in one catalytic site makes the surface electrostatic potential in the distal catalytic site more negative, thus enhancing binding of the second Mg(2+). Taken together, our results shed light on the structural and electrostatic factors that affect site-specific catalysis by this class of endonucleases.
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