8OXP

ATM(Q2971A) in complex with Mg AMP-PNP

8OXP の概要

• エントリーDOI: 10.2210/pdb8oxp/pdb
• EMDBエントリー: 17267
• 分子名称: Serine-protein kinase ATM, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: ataxia-telangiectasia mutated, atm, kinase, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 731202.94

構造登録者

Howes, A.C.,Perisic, O.,Williams, R.L. (登録日: 2023-05-02, 公開日: 2023-09-27, 最終更新日: 2023-10-11)

主引用文献

Howes, A.C.,Perisic, O.,Williams, R.L.
Structural insights into the activation of ataxia-telangiectasia mutated by oxidative stress.
Sci Adv, 9:eadi8291-eadi8291, 2023

PubMed Abstract: Ataxia-telangiectasia mutated (ATM) is a master kinase regulating DNA damage response that is activated by DNA double-strand breaks. However, ATM is also directly activated by reactive oxygen species, but how oxidative activation is achieved remains unknown. We determined the cryo-EM structure of an HO-activated ATM and showed that under oxidizing conditions, ATM formed an intramolecular disulfide bridge between two protomers that are rotated relative to each other when compared to the basal state. This rotation is accompanied by release of the substrate-blocking PRD region and twisting of the N-lobe relative to the C-lobe, which greatly optimizes catalysis. This active site remodeling enabled us to capture a substrate (p53) bound to the enzyme. This provides the first structural insights into how ATM is activated during oxidative stress.

PubMed: 37756394
DOI: 10.1126/sciadv.adi8291

実験手法

ELECTRON MICROSCOPY (2.6 Å)