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.
Structure factors resolution 2.162 rfactor 0.1682 rfree 0.2072
DPI 0.34 theoretical min: 0.20

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