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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 2no3 | ||||||
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タイトル | Novel 4-anilinopyrimidines as potent JNK1 Inhibitors | ||||||
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![]() | SIGNALING PROTEIN/INHIBITOR / JNK1 / C-JUN N-TERMINAL KINASE / JNK1 INHIBITORS / ANILINOPYRIMIDINES JNK1 INHIBITORS / SIGNALING PROTEIN-INHIBITOR COMPLEX | ||||||
機能・相同性 | ![]() positive regulation of cell killing / JUN phosphorylation / Interleukin-38 signaling / Activation of BMF and translocation to mitochondria / basal dendrite / Activation of BIM and translocation to mitochondria / JUN kinase activity / WNT5:FZD7-mediated leishmania damping / positive regulation of cyclase activity / histone deacetylase regulator activity ...positive regulation of cell killing / JUN phosphorylation / Interleukin-38 signaling / Activation of BMF and translocation to mitochondria / basal dendrite / Activation of BIM and translocation to mitochondria / JUN kinase activity / WNT5:FZD7-mediated leishmania damping / positive regulation of cyclase activity / histone deacetylase regulator activity / positive regulation of NLRP3 inflammasome complex assembly / NRAGE signals death through JNK / Activation of the AP-1 family of transcription factors / Fc-epsilon receptor signaling pathway / mitogen-activated protein kinase / regulation of macroautophagy / response to UV / stress-activated MAPK cascade / response to mechanical stimulus / protein serine/threonine kinase binding / energy homeostasis / JNK cascade / cellular response to cadmium ion / positive regulation of protein metabolic process / NRIF signals cell death from the nucleus / cellular response to amino acid starvation / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / negative regulation of protein binding / FCERI mediated MAPK activation / peptidyl-threonine phosphorylation / regulation of circadian rhythm / histone deacetylase binding / cellular response to reactive oxygen species / cellular response to mechanical stimulus / regulation of protein localization / cellular senescence / Signaling by ALK fusions and activated point mutants / rhythmic process / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / cellular response to oxidative stress / peptidyl-serine phosphorylation / cellular response to lipopolysaccharide / protein phosphatase binding / Oxidative Stress Induced Senescence / response to oxidative stress / positive regulation of apoptotic process / axon / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / synapse / positive regulation of gene expression / negative regulation of apoptotic process / enzyme binding / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | ![]() ![]() | ||||||
![]() | Abad-Zapatero, C. | ||||||
![]() | ![]() タイトル: Discovery of a new class of 4-anilinopyrimidines as potent c-Jun N-terminal kinase inhibitors: Synthesis and SAR studies. 著者: Liu, M. / Wang, S. / Clampit, J.E. / Gum, R.J. / Haasch, D.L. / Rondinone, C.M. / Trevillyan, J.M. / Abad-Zapatero, C. / Fry, E.H. / Sham, H.L. / Liu, G. #1: ![]() タイトル: Synthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors. 著者: Liu, M. / Xin, Z. / Clampit, J.E. / Wang, S. / Gum, R.J. / Haasch, D.L. / Trevillyan, J.M. / Abad-Zapatero, C. / Fry, E.H. / Sham, H.L. #2: ![]() タイトル: Selective aminopyridine-based C-Jun N-terminal kinase inhibitors with cellular activiy 著者: Szczepankiewicz, B.G. / Kosogof, C. / Nelson, L.T.J. / Liu, G. / Zhao, H. / Serby, M.D. / Xin, Z. / Liu, B. / Gum, R.J. / Haasch, D. #3: ![]() タイトル: Discovery of Potent, Highly Selective and orally bioavailable Pyridine Carboxamide C-jun NH2-terminal kinase inhibitors 著者: Zhao, H. / Serby, M.D. / Xin, Z. / Szczepankiewicz, B.G. / Liu, M. / Kosogof, C. / Liu, B. / Gum, R.J. / Clampit, J.E. / Haasch, D.L. | ||||||
履歴 |
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Remark 999 | SEQUENCE THE NATIVE, UNMUTATED SEQUENCE IS THE SAME AS THE P45983-2 ISOFORM. THE INTRODUCED ...SEQUENCE THE NATIVE, UNMUTATED SEQUENCE IS THE SAME AS THE P45983-2 ISOFORM. THE INTRODUCED MUTATIONS (THR183>GLU, TYR185>GLU) ARE INTENDED TO MIMIC THE ACTIVATED FORM OF THE KINASE UPON PHOSPHORYLATION OF THOSE TWO RESIDUES. |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 160.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 128.1 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 2h96S S: 精密化の開始モデル |
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類似構造データ |
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リンク
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集合体
登録構造単位 | ![]()
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単位格子 |
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要素
#1: タンパク質 | 分子量: 42919.559 Da / 分子数: 2 / 断片: JNK1 residues 1-364 / 変異: T183E, Y183E / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #2: タンパク質・ペプチド | 分子量: 1345.612 Da / 分子数: 2 / 断片: PEPJIP1 PEPTIDE / 由来タイプ: 合成 / 詳細: The sequence is found naturally in homo sapiens #3: 化合物 | ChemComp-SO4 / #4: 化合物 | |
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-実験情報
-実験
実験 | 手法: ![]() |
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試料調製
結晶 | マシュー密度: 4.97 Å3/Da / 溶媒含有率: 75.24 % |
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結晶化 | 温度: 277 K / 手法: 蒸気拡散法 / pH: 6.2 詳細: PROTEIN WAS PREINCUBATED WITH THE JIP1 PEPTIDE AT A 5X MOLAR EXCESS. PROTEIN CONCENTRATION 9- 12.6 MG/ML. HANGING DROPS CONSISTED OF 2UL PROTEIN PLUS 2 UL WELL SOLUTION. WELL SOLUTION:2.8-3.1 ...詳細: PROTEIN WAS PREINCUBATED WITH THE JIP1 PEPTIDE AT A 5X MOLAR EXCESS. PROTEIN CONCENTRATION 9- 12.6 MG/ML. HANGING DROPS CONSISTED OF 2UL PROTEIN PLUS 2 UL WELL SOLUTION. WELL SOLUTION:2.8-3.1 M AMMONIUM SULFATE, 10- 14% GLYCEROL. FOR CO-CRYSTALLIZATION EXPERIMENT WITH THE COMPOUND, THE COMPOUND WAS DISSOLVED IN DMSO AT 100 MM CONCENTRATION. ALLOW TO INCUBATE FOR AT LEAST AN HOUR ON ICE. SOLUTION WAS SPUN FOR 5 MINUTES AT 2000G PRIOR TO SETTING UP FOR CRYSTALLIZATION., pH 6.20, VAPOR DIFFUSION, temperature 277.0K |
-データ収集
回折 | 平均測定温度: 110 K |
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放射光源 | 由来: ![]() |
検出器 | タイプ: MAR CCD 165 mm / 検出器: CCD / 日付: 2005年1月6日 / 詳細: Osmic Mirrors |
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 1.5418 Å / 相対比: 1 |
反射 | 解像度: 3.2→20 Å / Num. all: 28588 / Num. obs: 27814 / % possible obs: 94.5 % / Observed criterion σ(I): 1 / 冗長度: 5.6 % / Biso Wilson estimate: 36.8 Å2 / Rmerge(I) obs: 0.083 / Rsym value: 0.083 / Net I/σ(I): 15.3 |
反射 シェル | 解像度: 3.2→3.31 Å / 冗長度: 4.2 % / Rmerge(I) obs: 0.454 / Mean I/σ(I) obs: 1.6 / Num. unique all: 2866 / Rsym value: 0.812 / % possible all: 98.3 |
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解析
ソフトウェア |
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精密化 | 構造決定の手法: ![]() 開始モデル: entry 2h96 解像度: 3.2→19.98 Å / Rfactor Rfree error: 0.006 / Data cutoff high absF: 162862.68 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / 交差検証法: THROUGHOUT / σ(F): 2 / 立体化学のターゲット値: Engh & Huber
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溶媒の処理 | 溶媒モデル: FLAT MODEL / Bsol: 24.1807 Å2 / ksol: 0.224291 e/Å3 | |||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 65.1 Å2
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Refine analyze |
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精密化ステップ | サイクル: LAST / 解像度: 3.2→19.98 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 3.2→3.31 Å / Rfactor Rfree error: 0.027 / Total num. of bins used: 10
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Xplor file |
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