7ZBG

Human Topoisomerase II Beta ATPase ADP

7ZBG の概要

• エントリーDOI: 10.2210/pdb7zbg/pdb
• 分子名称: DNA topoisomerase 2-beta, ADENOSINE-5'-DIPHOSPHATE, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: dna topoisomerase ii beta, human, atpase domain, top2b, dna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46785.72

構造登録者

Ling, E.M.,Basle, A.,Cowell, I.G.,Blower, T.R.,Austin, C.A. (登録日: 2022-03-23, 公開日: 2022-05-25, 最終更新日: 2024-01-31)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.3 Å)