EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular basis of human ATM kinase inhibition.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 28, Issue 10, Page 789-798, Year 2021
掲載日	2021年9月23日
著者	K Stakyte / M Rotheneder / K Lammens / J D Bartho / U Grädler / T Fuchß / U Pehl / A Alt / E van de Logt / K P Hopfner /
PubMed 要旨	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.
リンク	Nat Struct Mol Biol / PubMed:34556870
手法	EM (単粒子)
解像度	2.78 - 3.34 Å
構造データ	EMDB-12343: human ATM kinase with bound inhibitor KU-55933 手法: EM (単粒子) / 解像度: 2.78 Å EMDB-12345: human ATM Pincer domain 手法: EM (単粒子) / 解像度: 3.34 Å EMDB-12346: Human ATM Kinase Pincer-Spiral domains 手法: EM (単粒子) / 解像度: 3.06 Å EMDB-12347: Human ATM Spiral domain 手法: EM (単粒子) / 解像度: 3.1 Å 12350 7ni4 EMDB-12350, PDB-7ni4: Human ATM kinase domain with bound M4076 inhibitor 手法: EM (単粒子) / 解像度: 3.0 Å 12351 7ni5 EMDB-12351: Human ATM kinase with bound inhibitor KU-55933 (composite structure) PDB-7ni5: Human ATM kinase with bound inhibitor KU-55933 手法: EM (単粒子) / 解像度: 2.78 Å 12352 7ni6 EMDB-12352, PDB-7ni6: Human ATM kinase with bound ATPyS 手法: EM (単粒子) / 解像度: 2.8 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-UGK: 8-(1,3-dimethylpyrazol-4-yl)-1-(3-fluoranyl-5-methoxy-pyridin-4-yl)-7-methoxy-3-methyl-imidazo[4,5-c]quinolin-2-one ChemComp-UF8: 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one / KU-55933 ChemComp-AGS: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-γ-S / ATP-gamma-S, エネルギー貯蔵分子類似体YM ChemComp-MG*: Unknown entry / マグネシウムジカチオン
由来	homo sapiens (ヒト)
キーワード	SIGNALING PROTEIN / Kinase / inhibitor / DNA damage response / cancer research