+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6s4i | ||||||
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タイトル | Crystal structure of zinc free A14E, B25H, B29K(N(eps)-[2-(2-[2-(2-[2-(Octadecandioyl-gamma-Glu)amino]ethoxy)ethoxy]acetylamino)ethoxy]ethoxy)acetyl]), desB30 human insulin | ||||||
要素 | (Insulinインスリン) x 2 | ||||||
キーワード | HORMONE (ホルモン) / insulin (インスリン) / oral / dimer / zinc free | ||||||
機能・相同性 | 機能・相同性情報 negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / Signaling by Insulin receptor / IRS activation / nitric oxide-cGMP-mediated signaling / negative regulation of fatty acid metabolic process / Insulin processing / negative regulation of feeding behavior / regulation of protein secretion ...negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / Signaling by Insulin receptor / IRS activation / nitric oxide-cGMP-mediated signaling / negative regulation of fatty acid metabolic process / Insulin processing / negative regulation of feeding behavior / regulation of protein secretion / positive regulation of peptide hormone secretion / Regulation of gene expression in beta cells / positive regulation of respiratory burst / positive regulation of dendritic spine maintenance / alpha-beta T cell activation / negative regulation of acute inflammatory response / negative regulation of respiratory burst involved in inflammatory response / negative regulation of protein secretion / fatty acid homeostasis / Synthesis, secretion, and deacylation of Ghrelin / positive regulation of glycogen biosynthetic process / positive regulation of lipid biosynthetic process / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of gluconeogenesis / positive regulation of nitric oxide mediated signal transduction / regulation of protein localization to plasma membrane / COPI-mediated anterograde transport / negative regulation of lipid catabolic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / positive regulation of insulin receptor signaling pathway / negative regulation of reactive oxygen species biosynthetic process / 小胞 / positive regulation of protein autophosphorylation / Insulin receptor recycling / insulin-like growth factor receptor binding / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / neuron projection maintenance / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of brown fat cell differentiation / activation of protein kinase B activity / positive regulation of glycolytic process / Insulin receptor signalling cascade / positive regulation of mitotic nuclear division / Regulation of insulin secretion / positive regulation of nitric-oxide synthase activity / positive regulation of long-term synaptic potentiation / endosome lumen / positive regulation of cytokine production / acute-phase response / positive regulation of protein secretion / regulation of transmembrane transporter activity / positive regulation of cell differentiation / positive regulation of glucose import / negative regulation of proteolysis / regulation of synaptic plasticity / wound healing / insulin receptor binding / negative regulation of protein catabolic process / positive regulation of neuron projection development / hormone activity / 認識 / Golgi lumen / vasodilation / positive regulation of protein localization to nucleus / glucose metabolic process / regulation of protein localization / glucose homeostasis / cell-cell signaling / insulin receptor signaling pathway / positive regulation of NF-kappaB transcription factor activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of cell growth / secretory granule lumen / protease binding / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of cell migration / G protein-coupled receptor signaling pathway / Amyloid fiber formation / 小胞体 / ゴルジ体 / negative regulation of gene expression / positive regulation of cell population proliferation / positive regulation of gene expression / regulation of DNA-templated transcription / extracellular space / extracellular region / identical protein binding 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | X線回折 / 単波長異常分散 / 解像度: 1.511 Å | ||||||
データ登録者 | Johansson, E. | ||||||
引用 | ジャーナル: Nat Commun / 年: 2020 タイトル: Molecular engineering of safe and efficacious oral basal insulin. 著者: Hubalek, F. / Refsgaard, H.H.F. / Gram-Nielsen, S. / Madsen, P. / Nishimura, E. / Munzel, M. / Brand, C.L. / Stidsen, C.E. / Claussen, C.H. / Wulff, E.M. / Pridal, L. / Ribel, U. / ...著者: Hubalek, F. / Refsgaard, H.H.F. / Gram-Nielsen, S. / Madsen, P. / Nishimura, E. / Munzel, M. / Brand, C.L. / Stidsen, C.E. / Claussen, C.H. / Wulff, E.M. / Pridal, L. / Ribel, U. / Kildegaard, J. / Porsgaard, T. / Johansson, E. / Steensgaard, D.B. / Hovgaard, L. / Glendorf, T. / Hansen, B.F. / Jensen, M.K. / Nielsen, P.K. / Ludvigsen, S. / Rugh, S. / Garibay, P.W. / Moore, M.C. / Cherrington, A.D. / Kjeldsen, 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 | 6s4i.cif.gz | 41.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6s4i.ent.gz | 32.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6s4i.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/s4/6s4i ftp://data.pdbj.org/pub/pdb/validation_reports/s4/6s4i | 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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単位格子 |
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-要素
#1: タンパク質・ペプチド | 分子量: 2349.638 Da / 分子数: 1 / 変異: Y14E / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: INS / 発現宿主: Saccharomyces cerevisiae (パン酵母) / 参照: UniProt: P01308 | ||||
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#2: タンパク質・ペプチド | 分子量: 3323.822 Da / 分子数: 1 / 変異: F25H,des30 / 由来タイプ: 組換発現 詳細: Insulin B chain LYS B29 CHEMICALLY MODIFIED WITH [2-(2-[2-(2-[2-(Octadecandioyl-gamma-Glu)amino]ethoxy)ethoxy]acetylamino)ethoxy]ethoxy)acetyl] 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: INS / 発現宿主: Saccharomyces cerevisiae (パン酵母) / 参照: UniProt: P01308 | ||||
#3: 化合物 | #4: 水 | ChemComp-HOH / | 研究の焦点であるリガンドがあるか | N | |
-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: 3.42 Å3/Da / 溶媒含有率: 64 % |
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結晶化 | 温度: 310 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 8.5 詳細: Protein solution: 25 mg/ml insulin added 0.1% (w/v) NVoy Precipitant: 6.0 M ammonium nitrate, 0.1 M Tris pH 8.5 |
-データ収集
回折 | 平均測定温度: 100 K / Serial crystal experiment: N |
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放射光源 | 由来: 回転陽極 / タイプ: RIGAKU MICROMAX-007 HF / 波長: 1.548 Å |
検出器 | タイプ: MAR CCD 165 mm / 検出器: CCD / 日付: 2009年10月12日 |
放射 | プロトコル: MAD / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 1.548 Å / 相対比: 1 |
反射 | 解像度: 1.511→31.63 Å / Num. obs: 12258 / % possible obs: 99.7 % / 冗長度: 25.2 % / Biso Wilson estimate: 26.66 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.05816 / Rpim(I) all: 0.009455 / Rrim(I) all: 0.05896 / Net I/σ(I): 54.75 |
反射 シェル | 解像度: 1.511→1.565 Å / 冗長度: 14.9 % / Rmerge(I) obs: 0.5101 / Mean I/σ(I) obs: 4.25 / Num. unique obs: 1201 / CC1/2: 0.923 / Rpim(I) all: 0.1337 / Rrim(I) all: 0.5285 / % possible all: 97.4 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 単波長異常分散 / 解像度: 1.511→31.63 Å / SU ML: 0.14 / 交差検証法: FREE R-VALUE / σ(F): 1.36 / 位相誤差: 21.05
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 40.03 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 1.511→31.63 Å
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拘束条件 |
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LS精密化 シェル |
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精密化 TLS | 手法: refined / Origin x: 20.629 Å / Origin y: 38.6419 Å / Origin z: 28.2937 Å
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精密化 TLSグループ | Selection details: all |