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National Chung Hsing University Institutional Repository - NCHUIR > 中興大學 > 期刊論文 >  Structural Basis of Type II Topoisomerase Inhibition by the Anticancer Drug Etoposide

Please use this identifier to cite or link to this item: http://nchuir.lib.nchu.edu.tw/handle/309270000/140023

標題: Structural Basis of Type II Topoisomerase Inhibition by the Anticancer Drug Etoposide
作者: Wu, C.C.;Li, T.K.;Farh, L.;Lin, L.Y.;Lin, T.S.;Yu, Y.J.;Yen, T.J.;Chiang, C.W.;Chan, N.L.
關鍵字: dna topoisomerases;cleavage;cancer;enzyme;alpha;beta;substituents;chemotherapy;perspective;resistance
日期: 2011
Issue Date: 2012-12-14 15:36:11 (UTC+8)
關連: Science, Volume 333, Issue 6041, Page(s) 459-462.
摘要: Type II topoisomerases (TOP2s) resolve the topological problems of DNA by transiently cleaving both strands of a DNA duplex to form a cleavage complex through which another DNA segment can be transported. Several widely prescribed anticancer drugs increase the population of TOP2 cleavage complex, which leads to TOP2-mediated chromosome DNA breakage and death of cancer cells. We present the crystal structure of a large fragment of human TOP2 beta complexed to DNA and to the anticancer drug etoposide to reveal structural details of drug-induced stabilization of a cleavage complex. The interplay between the protein, the DNA, and the drug explains the structure-activity relations of etoposide derivatives and the molecular basis of drug-resistant mutations. The analysis of protein-drug interactions provides information applicable for developing an isoform-specific TOP2-targeting strategy.
Relation: Science
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[中興大學] 期刊論文

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