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3WE4

Crystal structure of S6K1 kinase domain in complex with a pyrimidine derivative PF-4708671 2-{[4-(5-ethylpyrimidin-4-yl)piperazin-1-yl]methyl}-5-(trifluoromethyl)-1H-benzimidazole

3WE4 の概要
エントリーDOI10.2210/pdb3we4/pdb
関連するPDBエントリー3WF5 3WF6 3WF7 3WF8 3WF9
分子名称Ribosomal protein S6 kinase beta-1, ZINC ION, 2-{[4-(5-ethylpyrimidin-4-yl)piperazin-1-yl]methyl}-5-(trifluoromethyl)-1H-benzimidazole, ... (4 entities in total)
機能のキーワードserine/threonine protein kinase domain, transferase, phosphorylation, atp-binding, zinc-binding, transferase-transferase inhibitor complex, transferase/transferase inhibitor
由来する生物種Homo sapiens (human)
細胞内の位置Cell junction, synapse, synaptosome . Isoform Alpha I: Nucleus. Isoform Alpha II: Cytoplasm: P23443
タンパク質・核酸の鎖数1
化学式量合計37634.63
構造登録者
Niwa, H.,Shirouzu, M.,Yokoyama, S. (登録日: 2013-06-29, 公開日: 2014-08-06, 最終更新日: 2023-11-08)
主引用文献Niwa, H.,Mikuni, J.,Sasaki, S.,Tomabechi, Y.,Honda, K.,Ikeda, M.,Ohsawa, N.,Wakiyama, M.,Handa, N.,Shirouzu, M.,Honma, T.,Tanaka, A.,Yokoyama, S.
Crystal structures of the S6K1 kinase domain in complexes with inhibitors
J.Struct.Funct.Genom., 15:153-164, 2014
Cited by
PubMed Abstract: Ribosomal protein S6 kinase 1 (S6K1) is a serine/threonine protein kinase that plays an important role in the PIK3/mTOR signaling pathway, and is implicated in diseases including diabetes, obesity, and cancer. The crystal structures of the S6K1 kinase domain in complexes with staurosporine and the S6K1-specific inhibitor PF-4708671 have been reported. In the present study, five compounds (F108, F109, F176, F177, and F179) were newly identified by in silico screening of a chemical library and kinase assay. The crystal structures of the five inhibitors in complexes with the S6K1 kinase domain were determined at resolutions between 1.85 and 2.10 Å. All of the inhibitors bound to the ATP binding site, lying along the P-loop, while the activation loop stayed in the inactive form. Compound F179, with a carbonyl group in the middle of the molecule, altered the αC helix conformation by interacting with the invariant Lys123. Compounds F176 and F177 bound slightly distant from the hinge region, and their sulfoamide groups formed polar interactions with the protein. The structural features required for the specific binding of inhibitors are discussed.
PubMed: 25078151
DOI: 10.1007/s10969-014-9188-8
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (1.995 Å)
構造検証レポート
Validation report summary of 3we4
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-10-30に公開中

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