ArticleNucleic acids research2021
Caught in motion: human NTHL1 undergoes interdomain rearrangement necessary for catalysis.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- A unified catalytic mechanism in bifunctional DNA glycosylases with an evolutionarily conserved aspartate-lysine dyad.Nature communications · 2026Article
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- A SMUG1 Inhibitor Modulates the Excision of Pyrimidine DNA Damage.ACS medicinal chemistry letters · 2026Article
- A monofunctional-like mutant of DNA glycosylase NTHL1 changes the dynamics of DNA repair during acute oxidative stress.The Journal of biological chemistry · 2026Article
- The S180R Human Germline Variant of DNA Polymerase β Is a Low Fidelity Enzyme with Reduced Flexibility of the Fingers Domain.Biochemistry · 2026Article
- Giving an Enzyme Scissors: Serotonin Derivatives as Potent Organocatalytic Switches for DNA Repair Enzyme OGG1.Journal of medicinal chemistry · 2025Article
- Translesion synthesis and microhomology-mediated end-joining repair in trypanosomatids.PLoS neglected tropical diseases · 2025Review
- Chemical Switching: A Concept Inspired by Strategies from Biocatalysis and Organocatalysis.Chembiochem : a European journal of chemical biology · 2025Review
- A prognostic signature derived from ac4C-associated genes stratifies survival and tumor immune microenvironment in cutaneous melanoma.Frontiers in immunology · 2025Article
- Integrating next-generation sequencing and artificial intelligence for the identification and validation of pathogenic variants in colorectal cancer.Frontiers in oncology · 2025Article
- OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization.Nature methods · 2024Article
- The Ribonuclease ZC3H12A is required for self-inflicted DNA breaks after DNA damage in small cell lung cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Enhanced Sampling for Conformational Changes and Molecular Mechanisms of Human NTHL1.The journal of physical chemistry letters · 2024Article
- Article
- Sequencing for oxidative DNA damage at single-nucleotide resolution with click-code-seq v2.0.Chemical communications (Cambridge, England) · 2023Article
- Maintenance of genome integrity by the late-acting cytoplasmic iron-sulfur assembly (CIA) complex.Frontiers in genetics · 2023Review
- Article
- Disentangling Unusual Catalytic Properties and the Role of the [4Fe-4S] Cluster of Three Endonuclease III from the ExtremophileMolecules (Basel, Switzerland) · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Base excision repair (BER) is the main pathway protecting cells from the continuous damage to DNA inflicted by reactive oxygen species. BER is initiated by DNA glycosylases, each of which repairs a particular class of base damage. NTHL1, a bifunctional DNA glycosylase, possesses both glycolytic and β-lytic activities with a preference for oxidized pyrimidine substrates. Defects in human NTHL1 drive a class of polyposis colorectal cancer. We report the first X-ray crystal structure of hNTHL1, revealing an open conformation not previously observed in the bacterial orthologs. In this conformation, the six-helical barrel domain comprising the helix-hairpin-helix (HhH) DNA binding motif is tipped away from the iron sulphur cluster-containing domain, requiring a conformational change to assemble a catalytic site upon DNA binding. We found that the flexibility of hNTHL1 and its ability to adopt an open configuration can be attributed to an interdomain linker. Swapping the human linker sequence for that of Escherichia coli yielded a protein chimera that crystallized in a closed conformation and had a reduced activity on lesion-containing DNA. This large scale interdomain rearrangement during catalysis is unprecedented for a HhH superfamily DNA glycosylase and provides important insight into the molecular mechanism of hNTHL1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.