ArticleJournal of molecular biology2012
The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 226 citations in OpenAlex.
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- Structure-Based Drug Design Targeting Topoisomerase II Alpha: Discovery of Potential Antitumor Xanthone Derivatives.Molecules (Basel, Switzerland) · 2026Article
- DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026Review
- Supercoiled DNA recognition and cleavage control in topoisomerase VI.Nature communications · 2026Article
- Coumarin-Augmented Thiazole Hybrids as Dual Anticancer and Antibacterial Agents.Chemical biology & drug design · 2026Article
- Mechanistic pathways andIranian journal of basic medical sciences · 2026Article
- Farnesiferol C enhances the effects of chemotherapy and ionising radiation in human melanoma cells via targeting topoisomerase II alpha.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- New protostane triterpenoids and their bioactivities from the fruits of Schinus terebinthifolius.Journal of natural medicines · 2025Article
- Topobexin targets the Topoisomerase II ATPase domain for beta isoform-selective inhibition and anthracycline cardioprotection.Nature communications · 2025Article
- Anticancer activity ofHeliyon · 2025Article
- Quinolin-4-ones: Methods of Synthesis and Application in Medicine.Molecules (Basel, Switzerland) · 2025Review
- Topoisomerase II Inhibition in Cancer: A Focus on Metal Complexes.Mini reviews in medicinal chemistry · 2025Review
- Identification and evaluation of candidate COVID-19 critical genes and medicinal drugs related to plasma cells.BMC infectious diseases · 2024Article
- Structural insights into the assembly of type IIA topoisomerase DNA cleavage-religation center.Nucleic acids research · 2024Article
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- In vitro evolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells.Scientific reports · 2024Article
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- Design, synthesis and in vitro anticancer activity of some new lomefloxacin derivatives.Scientific reports · 2024Article
- A unified view on enzyme catalysis by cryo-EM study of a DNA topoisomerase.Communications chemistry · 2024Article
60 more citing papers are in PubMed but not listed here.
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5 authors at 3 institutions in 2 countries.
Funding
Abstract
Type II topoisomerases are required for the management of DNA superhelicity and chromosome segregation, and serve as frontline targets for a variety of small-molecule therapeutics. To better understand how these enzymes act in both contexts, we determined the 2.9-Å-resolution structure of the DNA cleavage core of human topoisomerase IIα (TOP2A) bound to a doubly nicked, 30-bp duplex oligonucleotide. In accord with prior biochemical and structural studies, TOP2A significantly bends its DNA substrate using a bipartite, nucleolytic center formed at an N-terminal dimerization interface of the cleavage core. However, the protein also adopts a global conformation in which the second of its two inter-protomer contact points, one at the C-terminus, has separated. This finding, together with comparative structural analyses, reveals that the principal site of DNA engagement undergoes highly quantized conformational transitions between distinct binding, cleavage, and drug-inhibited states that correlate with the control of subunit-subunit interactions. Additional consideration of our TOP2A model in light of an etoposide-inhibited complex of human topoisomerase IIβ (TOP2B) suggests possible modification points for developing paralog-specific inhibitors to overcome the tendency of topoisomerase II-targeting chemotherapeutics to generate secondary malignancies.
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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.