topoisomerasetypeiistructures(存儲(chǔ)版)
【正文】 stress and keep the cell’s pact geic structure ? This is an essential function for cell functionality and survival, and so all anisms have at least one type of Type II topoisomerase! Berger amp。 Dong 2020 Model ? Summary ? Conclusions ? Impact ? Limitations ? Comparison to Previous Models – Berger et al Model 1996 – Rybenkov et al Model 1997 – Vologodskii et al Model 2020 Berger and Dong 2020 Model Summary ? The molecular understanding of DNA binding to Topo II was examined ? Crystallization of the Topo IIDNA plex was performed ? Crystallography determines the arrangement of atoms in solids Berger amp。 Nature, Vol. 379, Jan. 1996, pp. 225 – 232 ―Simplification of DNA Topology Below Equilibrium Values by Type II Topoisomerases‖ + Valentin Rybenkov et al。 pp. 3045 – 3049 ―An Antitumor DrugInduced Topoisomerase Cleavage Complex Blocks a Baccteriophage T4 Replication Fork in Vivo‖ + Gee Hong amp。 ―Multidrug Resistance Associated With Altered Topoisomerase II Activity—Topoisomerases II as Targets for Rational Drug Design‖ + Kenh Cowan amp。 Journal of the National Cancer Institute。 Mar 1984。 Carcinogenesis。 Vol. 98 No. 6。 Dong‘s current Topoisomerase Type II model Pharmaceuticals Summary ? Mammalian type II topoisomerases are targets of antitumor drug classes aminoacridines, anthracenediones, ellipticines, and epipodophyllotoxins. many of them interact with DNA by an intercalative mode ? Bacterial type II toposiomerases are targets of antibacterial gents quinolones and flouroquinolones. ? DNA intercalators are used in chemotherapeutic treatment to inhibit DNA replication in rapidly growing cancer cells. Ethidium intercalated between two adenineuracil base pairs. How does drug work on DNA? ? The drug ,localized precisely at the site of DNA cleavage, prevents topoisomerase from rejoining DNA breaks. ? Cleavage plexes themselves are not sufficient to cause cell death. ? Active cellular processes (transcription/replication) are necessary to transform cleavage plexes into cytotoxic lesions Complex by proteindenaturant treatmentNaDodSO4/alkali ? After binding to one segment of duplex DNA, a type II t
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