ArticleNucleic acids research2009
Evidence of the crucial role of the linker domain on the catalytic activity of human topoisomerase I by experimental and simulative characterization of the Lys681Ala mutant.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Arginine methylation of human DNA topoisomerase I by PRMT5 facilitates DNA relaxation.Nucleic acids research · 2026Article
- From Antarctica to cancer research: a novel human DNA topoisomerase 1B inhibitor from Antarctic spongeJournal of enzyme inhibition and medicinal chemistry · 2022Article
- Article
- In Vitro and In Silico Characterization of an Antimalarial Compound with Antitumor Activity Targeting Human DNA Topoisomerase IB.International journal of molecular sciences · 2021Article
- Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB.International journal of molecular sciences · 2021Review
- Swapping of The N-Terminal Domain of Human Topoisomerase 1B with the CorrespondingReports of biochemistry & molecular biology · 2020Article
- Distribution bias and biochemical characterization of TOP1MT single nucleotide variants.Scientific reports · 2017Article
- Recovery of the poisoned topoisomerase II for DNA religation: coordinated motion of the cleavage core revealed with the microsecond atomistic simulation.Nucleic acids research · 2015Article
- Simulations of DNA topoisomerase 1B bound to supercoiled DNA reveal changes in the flexibility pattern of the enzyme and a secondary protein-DNA binding site.Nucleic acids research · 2014Article
- Sequence selectivity of the cleavage sites induced by topoisomerase I inhibitors: a molecular dynamics study.Nucleic acids research · 2013Article
- Molecular mechanism of the camptothecin resistance of Glu710Gly topoisomerase IB mutant analyzed in vitro and in silico.Molecular cancer · 2013Article
- A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism.Bioscience reports · 2013Article
- Solvent dependency of the UV-Vis spectrum of indenoisoquinolines: role of keto-oxygens as polarity interaction probes.PloS one · 2013Article
- Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant.PloS one · 2013Article
- A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Role of Flexibility in Protein-DNA-Drug Recognition: The Case of Asp677Gly-Val703Ile Topoisomerase Mutant Hypersensitive to Camptothecin.Journal of amino acids · 2012Article
- Structural and dynamical effects induced by the anticancer drug topotecan on the human topoisomerase I - DNA complex.PloS one · 2010Article
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9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The functional and structural-dynamical properties of the Lys681Ala mutation in the human topoisomerase IB linker domain have been investigated by catalytic assays and molecular dynamics simulation. The mutant is characterized by a comparable cleavage and a strongly reduced religation rate when compared to the wild type protein. The mutant also displays perturbed linker dynamics, as shown by analysis of the principal components of the motion, and a reduced electrostatic interaction with DNA. Inspection of the inter atomic distances in proximity of the active site shows that in the mutant the distance between the amino group of Lys532 side chain and the 5' OH of the scissile phosphate is longer than the wild type enzyme, providing an atomic explanation for the reduced religation rate of the mutant. Taken together these results indicate the existence of a long range communication between the linker domain and the active site region and points out the crucial role of the linker in the modulation of the catalytic activity.
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