Summary
PDB 3QX3 deposited: 2011-03-01 modified: 2012-01-25
Title Human topoisomerase IIbeta in complex with DNA and etoposide
Authors Chan, N.L., Chiang, C.W., Farh, L., Lin, L.Y., Lin, T.S., Li, T.K., Wu, C.C., Yen, T.J., Yu, Y.J.
Method X-RAY DIFFRACTION
Structure factors resolution 2.162 rfactor 0.1682 rfree 0.2072
DPI 0.34 theoretical min: 0.20
Citations

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.

Science 2011 Jul; 333(6041):459-462 doi:10.1126/science.1204117

Cross References
Database source Identifier Description
PubMed 21778401 SCIEAS
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3QX3/1 3QX3 1 hexamer 0 6 8 11794