5ZRF

Crystal structure of human topoisomerase II beta in complex with 5-iodouridine-containing-DNA and etoposide in space group p21

Summary for 5ZRF

• Entry DOI: 10.2210/pdb5zrf/pdb
• Descriptor: DNA topoisomerase 2-beta, DNA (5'-D(P*AP*GP*CP*CP*GP*AP*GP*C)-3'), DNA/RNA (5'-R(P*(IU))-D(P*GP*CP*AP*GP*C)-R(P*(IU))-D(P*CP*GP*GP*C)-R(P*(IU))-3'), ... (6 entities in total)
• Functional Keywords: type ii topoisomerase, anti-cancer drug, topoii cleavage complex, isomerase-dna complex, isomerase-dna-isomerase inhibitor complex, isomerase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 198128.89

Authors

Chen, S.F.,Wang, Y.R.,Wu, C.C.,Chan, N.L. (deposition date: 2018-04-24, release date: 2018-08-08, Last modification date: 2024-10-16)

Primary citation

Chen, S.F.,Huang, N.L.,Lin, J.H.,Wu, C.C.,Wang, Y.R.,Yu, Y.J.,Gilson, M.K.,Chan, N.L.
Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate.
Nat Commun, 9:3085-3085, 2018

PubMed Abstract: Type IIA topoisomerases (Top2s) manipulate the handedness of DNA crossovers by introducing a transient and protein-linked double-strand break in one DNA duplex, termed the DNA-gate, whose opening allows another DNA segment to be transported through to change the DNA topology. Despite the central importance of this gate-opening event to Top2 function, the DNA-gate in all reported structures of Top2-DNA complexes is in the closed state. Here we present the crystal structure of a human Top2 DNA-gate in an open conformation, which not only reveals structural characteristics of its DNA-conducting path, but also uncovers unexpected yet functionally significant conformational changes associated with gate-opening. This structure further implicates Top2's preference for a left-handed DNA braid and allows the construction of a model representing the initial entry of another DNA duplex into the DNA-gate. Steered molecular dynamics calculations suggests the Top2-catalyzed DNA passage may be achieved by a rocker-switch-type movement of the DNA-gate.

PubMed: 30082834
DOI: 10.1038/s41467-018-05406-y

Experimental method

X-RAY DIFFRACTION (2.3 Å)