7ZBG

Human Topoisomerase II Beta ATPase ADP

Summary for 7ZBG

• Entry DOI: 10.2210/pdb7zbg/pdb
• Descriptor: DNA topoisomerase 2-beta, ADENOSINE-5'-DIPHOSPHATE, SULFATE ION, ... (6 entities in total)
• Functional Keywords: dna topoisomerase ii beta, human, atpase domain, top2b, dna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 46785.72

Authors

Ling, E.M.,Basle, A.,Cowell, I.G.,Blower, T.R.,Austin, C.A. (deposition date: 2022-03-23, release date: 2022-05-25, Last modification date: 2024-01-31)

Primary citation

Ling, E.M.,Basle, A.,Cowell, I.G.,van den Berg, B.,Blower, T.R.,Austin, C.A.
A comprehensive structural analysis of the ATPase domain of human DNA topoisomerase II beta bound to AMPPNP, ADP, and the bisdioxopiperazine, ICRF193.
Structure, 30:1129-1145.e3, 2022

PubMed Abstract: Human topoisomerase II beta (TOP2B) modulates DNA topology using energy from ATP hydrolysis. To investigate the conformational changes that occur during ATP hydrolysis, we determined the X-ray crystallographic structures of the human TOP2B ATPase domain bound to AMPPNP or ADP at 1.9 Å and 2.6 Å resolution, respectively. The GHKL domains of both structures are similar, whereas the QTK loop within the transducer domain can move for product release. As TOP2B is the clinical target of bisdioxopiperazines, we also determined the structure of a TOP2B:ADP:ICRF193 complex to 2.3 Å resolution and identified key drug-binding residues. Biochemical characterization revealed the N-terminal strap reduces the rate of ATP hydrolysis. Mutagenesis demonstrated residue E103 as essential for ATP hydrolysis in TOP2B. Our data provide fundamental insights into the tertiary structure of the human TOP2B ATPase domain and a potential regulatory mechanism for ATP hydrolysis.

PubMed: 35660158
DOI: 10.1016/j.str.2022.05.009

Experimental method

X-RAY DIFFRACTION (2.3 Å)