+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6dki | ||||||
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タイトル | Crystal structure of Trk-A in complex with the Pan-Trk Kinase Inhibitor, compound 19. | ||||||
要素 | High affinity nerve growth factor receptor | ||||||
キーワード | TRANSFERASE/TRANSFERASE INHIBITOR / Inhibitor Tyrosine kinase / TRANSFERASE / pan-Trk Kinase / Treatment for pain / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
機能・相同性 | 機能・相同性情報 behavioral response to formalin induced pain / neurotrophin p75 receptor binding / olfactory nerve development / response to hydrostatic pressure / TRKA activation by NGF / PLC-gamma1 signalling / Signalling to STAT3 / programmed cell death involved in cell development / mechanoreceptor differentiation / neurotrophin receptor activity ...behavioral response to formalin induced pain / neurotrophin p75 receptor binding / olfactory nerve development / response to hydrostatic pressure / TRKA activation by NGF / PLC-gamma1 signalling / Signalling to STAT3 / programmed cell death involved in cell development / mechanoreceptor differentiation / neurotrophin receptor activity / nerve growth factor receptor activity / neurotrophin binding / Sertoli cell development / GPI-linked ephrin receptor activity / nerve growth factor signaling pathway / axonogenesis involved in innervation / Retrograde neurotrophin signalling / nerve growth factor binding / NGF-independant TRKA activation / sympathetic nervous system development / Signalling to p38 via RIT and RIN / ARMS-mediated activation / positive regulation of Ras protein signal transduction / positive regulation of programmed cell death / positive regulation of synapse assembly / PI3K/AKT activation / Frs2-mediated activation / detection of temperature stimulus involved in sensory perception of pain / neurotrophin TRK receptor signaling pathway / neuron development / Signalling to RAS / response to axon injury / detection of mechanical stimulus involved in sensory perception of pain / response to electrical stimulus / peptidyl-tyrosine autophosphorylation / transmembrane receptor protein tyrosine kinase activity / B cell differentiation / positive regulation of synaptic transmission, glutamatergic / positive regulation of GTPase activity / response to nutrient levels / cellular response to nerve growth factor stimulus / axon guidance / receptor protein-tyrosine kinase / kinase binding / positive regulation of neuron projection development / peptidyl-tyrosine phosphorylation / cellular response to nicotine / circadian rhythm / recycling endosome membrane / positive regulation of angiogenesis / neuron projection development / late endosome / late endosome membrane / positive regulation of NF-kappaB transcription factor activity / early endosome membrane / protein tyrosine kinase activity / neuron apoptotic process / negative regulation of neuron apoptotic process / protein autophosphorylation / positive regulation of ERK1 and ERK2 cascade / early endosome / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / learning or memory / receptor complex / endosome membrane / response to xenobiotic stimulus / positive regulation of protein phosphorylation / protein phosphorylation / negative regulation of cell population proliferation / axon / neuronal cell body / dendrite / negative regulation of apoptotic process / cell surface / protein homodimerization activity / protein-containing complex / ATP binding / identical protein binding / plasma membrane 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: 2.11 Å | ||||||
データ登録者 | Greasley, S.E. / Johnson, E. / Kraus, M.L. / Cronin, C.N. | ||||||
引用 | ジャーナル: J. Med. Chem. / 年: 2018 タイトル: Discovery of Potent, Selective, and Peripherally Restricted Pan-Trk Kinase Inhibitors for the Treatment of Pain. 著者: Bagal, S.K. / Andrews, M. / Bechle, B.M. / Bian, J. / Bilsland, J. / Blakemore, D.C. / Braganza, J.F. / Bungay, P.J. / Corbett, M.S. / Cronin, C.N. / Cui, J.J. / Dias, R. / Flanagan, N.J. / ...著者: Bagal, S.K. / Andrews, M. / Bechle, B.M. / Bian, J. / Bilsland, J. / Blakemore, D.C. / Braganza, J.F. / Bungay, P.J. / Corbett, M.S. / Cronin, C.N. / Cui, J.J. / Dias, R. / Flanagan, N.J. / Greasley, S.E. / Grimley, R. / James, K. / Johnson, E. / Kitching, L. / Kraus, M.L. / McAlpine, I. / Nagata, A. / Ninkovic, S. / Omoto, K. / Scales, S. / Skerratt, S.E. / Sun, J. / Tran-Dube, M. / Waldron, G.J. / Wang, F. / Warmus, J.S. | ||||||
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 | 6dki.cif.gz | 76.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6dki.ent.gz | 55 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6dki.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
文書・要旨 | 6dki_validation.pdf.gz | 694.6 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6dki_full_validation.pdf.gz | 694.8 KB | 表示 | |
XML形式データ | 6dki_validation.xml.gz | 12.9 KB | 表示 | |
CIF形式データ | 6dki_validation.cif.gz | 18 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/dk/6dki ftp://data.pdbj.org/pub/pdb/validation_reports/dk/6dki | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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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: 36110.504 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NTRK1, MTC, TRK, TRKA 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P04629, receptor protein-tyrosine kinase |
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#2: 化合物 | ChemComp-22L / |
#3: 化合物 | ChemComp-GOD / |
#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: 2.28 Å3/Da / 溶媒含有率: 46.08 % |
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結晶化 | 温度: 294 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 8 詳細: Well volume: 20.0 uL Well Ingredients: Polymer: 9.0 %w/v (3.6 uL of stock 50.0 %w/v) PEG 3350 Buffer: 15.8 %v/v (3.16 uL of stock 100.0 %v/v) tacsimate (pH 8.00) Additive: 0.025 M (5.0 uL of ...詳細: Well volume: 20.0 uL Well Ingredients: Polymer: 9.0 %w/v (3.6 uL of stock 50.0 %w/v) PEG 3350 Buffer: 15.8 %v/v (3.16 uL of stock 100.0 %v/v) tacsimate (pH 8.00) Additive: 0.025 M (5.0 uL of stock 0.1 M) TCEP hydrochloride Plate setup temperature: 13 C Plate incubation temperature: 21 C Drop volume from well: 0.01 uL Drop protein volume: 0.2 uL Protein: 6.30 mg/mL |
-データ収集
回折 | 平均測定温度: 93 K |
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放射光源 | 由来: シンクロトロン / サイト: APS / ビームライン: 17-ID / 波長: 1 Å |
検出器 | タイプ: DECTRIS PILATUS3 S 6M / 検出器: PIXEL / 日付: 2013年6月13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: 1 Å / 相対比: 1 |
反射 | 解像度: 2.11→40.73 Å / Num. obs: 18843 / % possible obs: 99 % / 冗長度: 3.3 % / Biso Wilson estimate: 37.38 Å2 / Rsym value: 0.054 / Net I/σ(I): 12.9 |
反射 シェル | 解像度: 2.11→2.22 Å / 冗長度: 3.3 % / Num. unique obs: 2746 / Rsym value: 0.396 / % possible all: 99.7 |
-解析
ソフトウェア |
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精密化 | 解像度: 2.11→40.73 Å / Cor.coef. Fo:Fc: 0.9491 / Cor.coef. Fo:Fc free: 0.9306 / SU R Cruickshank DPI: 0.199 / 交差検証法: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.197 / SU Rfree Blow DPI: 0.169 / SU Rfree Cruickshank DPI: 0.171
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原子変位パラメータ | Biso mean: 39.71 Å2
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精密化ステップ | サイクル: 1 / 解像度: 2.11→40.73 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 2.11→2.24 Å / Total num. of bins used: 9
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