8OXM
ATM(Q2971A) activated by oxidative stress in complex with Mg AMP-PNP and p53 peptide
Summary for 8OXM
| Entry DOI | 10.2210/pdb8oxm/pdb |
| EMDB information | 17265 |
| Descriptor | Cellular tumor antigen p53, Serine-protein kinase ATM, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total) |
| Functional Keywords | ataxia-telangiectasia mutated, atm, kinase, oxidative stress, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 733927.82 |
| Authors | Howes, A.C.,Perisic, O.,Williams, R.L. (deposition date: 2023-05-02, release date: 2023-09-27, Last modification date: 2023-10-11) |
| Primary citation | 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 Cited by 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: 37756394DOI: 10.1126/sciadv.adi8291 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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