3QX3

Human topoisomerase IIbeta in complex with DNA and etoposide

Summary for 3QX3

• Entry DOI: 10.2210/pdb3qx3/pdb
• Related: 3QXK
• Descriptor: DNA topoisomerase 2-beta, DNA (5'-D(P*AP*GP*CP*CP*GP*AP*GP*C)-3'), DNA (5'-D(P*TP*GP*CP*AP*GP*CP*TP*CP*GP*GP*CP*T)-3'), ... (6 entities in total)
• Functional Keywords: toprim domain, winged-helix domain, coiled-coil domain, dna binding and cleavage, nucleus, isomerase-dna-isomerase inhibitor complex, isomerase/dna/isomerase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q02880
• Total number of polymer chains: 6
• Total formula weight: 197361.67

Authors

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. (deposition date: 2011-03-01, release date: 2011-07-06, Last modification date: 2023-11-01)

Primary citation

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.
Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide
Science, 333:459-462, 2011

PubMed Abstract: 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 TOP2β 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.

PubMed: 21778401
DOI: 10.1126/science.1204117

Experimental method

X-RAY DIFFRACTION (2.162 Å)