ArticleBiochemistry2014
High-resolution crystal structures reveal plasticity in the metal binding site of apurinic/apyrimidinic endonuclease I.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 65 citations in OpenAlex.
- How Do DICER1 Syndrome Mutations Disrupt Catalysis? Unveiling Dicer Metal Binding Architecture and Mechanism of Action Using MD Simulations and QM/MM Calculations.Journal of computational chemistry · 2026Article
- APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.Expert opinion on therapeutic targets · 2026Review
- Orchestrated metal ion repositioning defines the dynamic catalytic strategy of the essential DNA repair nuclease APE1.bioRxiv : the preprint server for biology · 2026Article
- APE1 coordinates its disordered region and metal cofactors to drive genome surveillance.Nucleic acids research · 2026Article
- Targeting APE1 endonuclease activity impairs metastasis and enhances genotoxic therapy response in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Endogenous promoter G-quadruplexes scaffold apurinic/apyrimidinic endonuclease (APE1) to drive gene expression.Nucleic acids research · 2026Article
- Characterization of the enzymatic activity of the rhythmic human NADP(H) phosphatase, Nocturnin.Archives of biochemistry and biophysics · 2026Article
- Targeting APE1 endonuclease activity impairs metastasis and enhances genotoxic therapy response in pancreatic cancer.Research square · 2025Article
- Chemically induced partial unfolding of the multifunctional apurinic/apyrimidinic endonuclease 1.Protein science : a publication of the Protein Society · 2025Review
- Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.Angiogenesis · 2025Article
- Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease.Nature communications · 2024Article
- A New Drug Discovery Platform: Application to DNA Polymerase Eta and Apurinic/Apyrimidinic Endonuclease 1.International journal of molecular sciences · 2023Article
- AUF1 Recognizes 8-Oxo-Guanosine Embedded in DNA and Stimulates APE1 Endoribonuclease Activity.Antioxidants & redox signaling · 2023Article
- Mechanistic insight into AP-endonuclease 1 cleavage of abasic sites at stalled replication fork mimics.Nucleic acids research · 2023Article
- Characterizing inhibitors of human AP endonuclease 1.PloS one · 2023Article
- Comparative Analysis of Exo- and Endonuclease Activities of APE1-like Enzymes.International journal of molecular sciences · 2022Article
- Structural dissection of sequence recognition and catalytic mechanism of human LINE-1 endonuclease.Nucleic acids research · 2021Article
- Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.International journal of molecular sciences · 2021Review
- Fragment- and structure-based drug discovery for developing therapeutic agents targeting the DNA Damage Response.Progress in biophysics and molecular biology · 2021Article
- Molecular Mechanisms Regulating the DNA Repair Protein APE1: A Focus on Its Flexible N-Terminal Tail Domain.International journal of molecular sciences · 2021Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Apurinic/apyrimidinic endonuclease I (APE1) is an essential base excision repair enzyme that catalyzes a Mg²⁺-dependent reaction in which the phosphodiester backbone is cleaved 5' of an abasic site in duplex DNA. This reaction has been proposed to involve either one or two metal ions bound to the active site. In the present study, we report crystal structures of Mg²⁺, Mn²⁺, and apo-APE1 determined at 1.4, 2.2, and 1.65 Å, respectively, representing two of the highest resolution structures yet reported for APE1. In our structures, a single well-ordered Mn²⁺ ion was observed coordinated by D70 and E96; the Mg²⁺ site exhibited disorder modeled as two closely positioned sites coordinated by D70 and E96 or E96 alone. Direct metal binding analysis of wild-type, D70A, and E96A APE1, as assessed by differential scanning fluorimetry, indicated a role for D70 and E96 in binding of Mg²⁺ or Mn²⁺ to APE1. Consistent with the disorder exhibited by Mg²⁺ bound to the active site, two different conformations of E96 were observed coordinated to Mg²⁺. A third conformation for E96 in the apo structure is similar to that observed in the APE1-DNA-Mg²⁺ complex structure. Thus, binding of Mg²⁺ in three different positions within the active site of APE1 in these crystal structures corresponds directly with three different conformations of E96. Taken together, our results are consistent with the initial capture of metal by D70 and E96 and repositioning of Mg²⁺ facilitated by the structural plasticity of E96 in the active site.
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