+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5ta8 | ||||||
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タイトル | Crystal structure of PLK1 in complex with a novel 5,6-dihydroimidazolo[1,5-f]pteridine inhibitor | ||||||
要素 | Serine/threonine-protein kinase PLK1 | ||||||
キーワード | Transferase/Transferase Inhibitor / PLK1 Inhibitor / Kinase (キナーゼ) / Structure-based drug design (医薬品設計) / Antitumor activity / Transferase-Transferase Inhibitor complex | ||||||
機能・相同性 | 機能・相同性情報 Mitotic Telophase/Cytokinesis / regulation of protein localization to cell cortex / Mitotic Metaphase/Anaphase Transition / Golgi inheritance / synaptonemal complex disassembly / Activation of NIMA Kinases NEK9, NEK6, NEK7 / homologous chromosome segregation / polo kinase / nuclear membrane disassembly / mitotic nuclear membrane disassembly ...Mitotic Telophase/Cytokinesis / regulation of protein localization to cell cortex / Mitotic Metaphase/Anaphase Transition / Golgi inheritance / synaptonemal complex disassembly / Activation of NIMA Kinases NEK9, NEK6, NEK7 / homologous chromosome segregation / polo kinase / nuclear membrane disassembly / mitotic nuclear membrane disassembly / protein localization to nuclear envelope / Phosphorylation of Emi1 / metaphase/anaphase transition of mitotic cell cycle / synaptonemal complex / female meiosis chromosome segregation / Phosphorylation of the APC/C / regulation of protein binding / anaphase-promoting complex binding / outer kinetochore / negative regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of ubiquitin protein ligase activity / regulation of mitotic spindle assembly / microtubule bundle formation / Polo-like kinase mediated events / Golgi Cisternae Pericentriolar Stack Reorganization / mitotic chromosome condensation / regulation of mitotic metaphase/anaphase transition / sister chromatid cohesion / positive regulation of ubiquitin-protein transferase activity / centrosome cycle / double-strand break repair via alternative nonhomologous end joining / regulation of mitotic cell cycle phase transition / mitotic spindle assembly checkpoint signaling / mitotic spindle pole / regulation of anaphase-promoting complex-dependent catabolic process / mitotic G2 DNA damage checkpoint signaling / positive regulation of proteolysis / mitotic sister chromatid segregation / establishment of mitotic spindle orientation / mitotic cytokinesis / centriolar satellite / spindle midzone / negative regulation of double-strand break repair via homologous recombination / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Cyclin A/B1/B2 associated events during G2/M transition / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / protein localization to chromatin / Resolution of Sister Chromatid Cohesion / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / regulation of mitotic cell cycle / 中心小体 / AURKA Activation by TPX2 / mitotic spindle organization / Condensation of Prophase Chromosomes / positive regulation of peptidyl-threonine phosphorylation / regulation of cytokinesis / RHO GTPases Activate Formins / protein destabilization / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / establishment of protein localization / 動原体 / 紡錘体 / spindle / positive regulation of protein localization to nucleus / Separation of Sister Chromatids / The role of GTSE1 in G2/M progression after G2 checkpoint / G2/M transition of mitotic cell cycle / microtubule cytoskeleton / Regulation of PLK1 Activity at G2/M Transition / double-strand break repair / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / mitotic cell cycle / midbody / microtubule binding / peptidyl-serine phosphorylation / regulation of cell cycle / protein ubiquitination / protein kinase activity / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / 中心体 / クロマチン / negative regulation of apoptotic process / protein kinase binding / negative regulation of transcription by RNA polymerase II / magnesium ion binding / 核質 / ATP binding / identical protein binding / 細胞核 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | X線回折 / シンクロトロン / 解像度: 2.6 Å | ||||||
データ登録者 | Skene, R.J. / Hosfield, D.J. | ||||||
引用 | ジャーナル: Bioorg. Med. Chem. Lett. / 年: 2017 タイトル: Structure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors. 著者: Kiryanov, A. / Natala, S. / Jones, B. / McBride, C. / Feher, V. / Lam, B. / Liu, Y. / Honda, K. / Uchiyama, N. / Kawamoto, T. / Hikichi, Y. / Zhang, L. / Hosfield, D. / Skene, R. / Zou, H. / ...著者: Kiryanov, A. / Natala, S. / Jones, B. / McBride, C. / Feher, V. / Lam, B. / Liu, Y. / Honda, K. / Uchiyama, N. / Kawamoto, T. / Hikichi, Y. / Zhang, L. / Hosfield, D. / Skene, R. / Zou, H. / Stafford, J. / Cao, X. / Ichikawa, T. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 5ta8.cif.gz | 140.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5ta8.ent.gz | 109.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5ta8.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ta/5ta8 ftp://data.pdbj.org/pub/pdb/validation_reports/ta/5ta8 | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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単位格子 |
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Components on special symmetry positions |
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-要素
#1: タンパク質 | 分子量: 40582.906 Da / 分子数: 1 / 断片: UNP residues 13-345 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PLK1, PLK / 発現宿主: unidentified baculovirus (ウイルス) / 参照: UniProt: P53350, polo kinase |
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#2: 化合物 | ChemComp-ZN / |
#3: 化合物 | ChemComp-79C / |
#4: 水 | ChemComp-HOH / |
-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 2.45 Å3/Da / 溶媒含有率: 49.83 % |
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結晶化 | 温度: 277 K / 手法: 蒸気拡散法, シッティングドロップ法 詳細: 0.95 mM succinic acid, 1.7% PEG2000 MME, 0.4 mM zinc acetate, 100 mM HEPES, pH 7.0, temperature 277K |
-データ収集
回折 | 平均測定温度: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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放射光源 | 由来: シンクロトロン / サイト: ALS / ビームライン: 5.0.3 / 波長: 0.987 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
検出器 | タイプ: ADSC QUANTUM 315r / 検出器: CCD / 日付: 2007年10月11日 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 0.987 Å / 相対比: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
反射 | 解像度: 2.6→50 Å / Num. obs: 9764 / % possible obs: 75.9 % / 冗長度: 6.5 % / Rmerge(I) obs: 0.079 / Χ2: 1.045 / Net I/av σ(I): 17.758 / Net I/σ(I): 12.6 / Num. measured all: 63440 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
反射 シェル |
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-解析
ソフトウェア |
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精密化 | 解像度: 2.6→46.31 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.931 / SU B: 31.645 / SU ML: 0.305 / SU R Cruickshank DPI: 0.2881 / 交差検証法: THROUGHOUT / σ(F): 0 / ESU R Free: 0.368 / 詳細: U VALUES : WITH TLS ADDED
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溶媒の処理 | イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso max: 184.71 Å2 / Biso mean: 94.267 Å2 / Biso min: 41.95 Å2
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精密化ステップ | サイクル: final / 解像度: 2.6→46.31 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 2.603→2.67 Å / Total num. of bins used: 20
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精密化 TLS | 手法: refined / Refine-ID: X-RAY DIFFRACTION
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精密化 TLSグループ |
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