- EMDB-12346: Human ATM Kinase Pincer-Spiral domains -
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Basic information
Entry
Database: EMDB / ID: EMD-12346
Title
Human ATM Kinase Pincer-Spiral domains
Map data
Sample
Complex: ATM dimer with bound KU-55933
Protein or peptide: Human ATM Spiral-Pincer domains
Function / homology
Function and homology information
establishment of RNA localization to telomere / positive regulation of telomerase catalytic core complex assembly / negative regulation of telomere capping / Sensing of DNA Double Strand Breaks / cellular response to nitrosative stress / peptidyl-serine autophosphorylation / establishment of protein-containing complex localization to telomere / meiotic telomere clustering / positive regulation of telomere maintenance via telomere lengthening / pre-B cell allelic exclusion ...establishment of RNA localization to telomere / positive regulation of telomerase catalytic core complex assembly / negative regulation of telomere capping / Sensing of DNA Double Strand Breaks / cellular response to nitrosative stress / peptidyl-serine autophosphorylation / establishment of protein-containing complex localization to telomere / meiotic telomere clustering / positive regulation of telomere maintenance via telomere lengthening / pre-B cell allelic exclusion / male meiotic nuclear division / histone mRNA catabolic process / extrinsic component of synaptic vesicle membrane / regulation of telomere maintenance via telomerase / female meiotic nuclear division / DNA double-strand break processing / lipoprotein catabolic process / regulation of autophagosome assembly / cellular response to X-ray / V(D)J recombination / pexophagy / oocyte development / Impaired BRCA2 binding to PALB2 / reciprocal meiotic recombination / DNA repair complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / Homologous DNA Pairing and Strand Exchange / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / 1-phosphatidylinositol-3-kinase activity / HDR through Single Strand Annealing (SSA) / response to ionizing radiation / positive regulation of double-strand break repair / Impaired BRCA2 binding to RAD51 / mitotic spindle assembly checkpoint signaling / negative regulation of B cell proliferation / TP53 Regulates Transcription of Caspase Activators and Caspases / cellular response to stress / mitotic G2 DNA damage checkpoint signaling / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / peroxisomal matrix / Presynaptic phase of homologous DNA pairing and strand exchange / replicative senescence / signal transduction in response to DNA damage / Regulation of HSF1-mediated heat shock response / somitogenesis / Pexophagy / regulation of cellular response to heat / ovarian follicle development / cellular response to retinoic acid / negative regulation of TORC1 signaling / positive regulation of telomere maintenance via telomerase / telomere maintenance / positive regulation of cell adhesion / DNA damage checkpoint signaling / Stabilization of p53 / thymus development / regulation of signal transduction by p53 class mediator / Autodegradation of the E3 ubiquitin ligase COP1 / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / post-embryonic development / double-strand break repair via homologous recombination / determination of adult lifespan / cellular response to reactive oxygen species / TP53 Regulates Transcription of DNA Repair Genes / Nonhomologous End-Joining (NHEJ) / DNA damage response, signal transduction by p53 class mediator / Regulation of TP53 Activity through Methylation / HDR through Homologous Recombination (HRR) / cellular response to gamma radiation / G2/M DNA damage checkpoint / brain development / DNA Damage/Telomere Stress Induced Senescence / Meiotic recombination / double-strand break repair via nonhomologous end joining / spindle / multicellular organism growth / Regulation of TP53 Degradation / intrinsic apoptotic signaling pathway in response to DNA damage / cellular senescence / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / site of double-strand break / double-strand break repair / positive regulation of neuron apoptotic process / Processing of DNA double-strand break ends / chromosome / heart development / protein autophosphorylation / Regulation of TP53 Activity through Phosphorylation / regulation of apoptotic process / neuron apoptotic process / non-specific serine/threonine protein kinase / regulation of cell cycle / regulation of autophagy / protein phosphorylation / positive regulation of cell migration Similarity search - Function
Telomere-length maintenance and DNA damage repair / Serine/threonine-protein kinase ATM, plant / ATM, catalytic domain / Telomere-length maintenance and DNA damage repair / Telomere-length maintenance and DNA damage repair / FATC domain / PIK-related kinase, FAT / FAT domain / FATC / FATC domain ...Telomere-length maintenance and DNA damage repair / Serine/threonine-protein kinase ATM, plant / ATM, catalytic domain / Telomere-length maintenance and DNA damage repair / Telomere-length maintenance and DNA damage repair / FATC domain / PIK-related kinase, FAT / FAT domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Armadillo-type fold / Protein kinase-like domain superfamily Similarity search - Domain/homology
Journal: Nat Struct Mol Biol / Year: 2021 Title: Molecular basis of human ATM kinase inhibition. Authors: K Stakyte / M Rotheneder / K Lammens / J D Bartho / U Grädler / T Fuchß / U Pehl / A Alt / E van de Logt / K P Hopfner / Abstract: Human checkpoint kinase ataxia telangiectasia-mutated (ATM) plays a key role in initiation of the DNA damage response following DNA double-strand breaks. ATM inhibition is a promising approach in ...Human checkpoint kinase ataxia telangiectasia-mutated (ATM) plays a key role in initiation of the DNA damage response following DNA double-strand breaks. ATM inhibition is a promising approach in cancer therapy, but, so far, detailed insights into the binding modes of known ATM inhibitors have been hampered due to the lack of high-resolution ATM structures. Using cryo-EM, we have determined the structure of human ATM to an overall resolution sufficient to build a near-complete atomic model and identify two hitherto unknown zinc-binding motifs. We determined the structure of the kinase domain bound to ATPγS and to the ATM inhibitors KU-55933 and M4076 at 2.8 Å, 2.8 Å and 3.0 Å resolution, respectively. The mode of action and selectivity of the ATM inhibitors can be explained by structural comparison and provide a framework for structure-based drug design.
History
Deposition
Feb 11, 2021
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Header (metadata) release
Sep 1, 2021
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Map release
Sep 1, 2021
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Update
Oct 20, 2021
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Current status
Oct 20, 2021
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
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