+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 3fq9 | ||||||
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タイトル | Design of an insulin analog with enhanced receptor-binding selectivity. Rationale, structure, and therapeutic implications | ||||||
要素 | (Insulinインスリン) x 2 | ||||||
キーワード | HORMONE (ホルモン) / receptor-binding / insulin design / rational / therapeutic implication / Carbohydrate metabolism (炭水化物代謝) / Cleavage on pair of basic residues / Diabetes mellitus (糖尿病) / Disease mutation / Glucose metabolism (炭水化物代謝) / Pharmaceutical (医薬品) / Secreted (分泌) | ||||||
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 / negative regulation of reactive oxygen species biosynthetic process / positive regulation of insulin receptor signaling pathway / 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 | ||||||
手法 | X線回折 / シンクロトロン / 分子置換 / 解像度: 1.35 Å | ||||||
データ登録者 | Zhao, M. / Wan, Z.L. / Whittaker, L. / Xu, B. / Phillips, N. / Katsoyannis, P. / Whittaker, J. / Weiss, M.A. | ||||||
引用 | ジャーナル: J.Biol.Chem. / 年: 2009 タイトル: Design of an insulin analog with enhanced receptor binding selectivity: rationale, structure, and therapeutic implications. 著者: Zhao, M. / Wan, Z.L. / Whittaker, L. / Xu, B. / Phillips, N.B. / Katsoyannis, P.G. / Ismail-Beigi, F. / Whittaker, J. / Weiss, M.A. #1: ジャーナル: Philos.Trans.R.Soc.London,Ser.B / 年: 1988 タイトル: The structure of 2zn pig insulin crystal at 1.5 A resolution 著者: Baker, E.N. / Blundell, T.L. / Cutfield, J.F. / Cutfield, S.M. / Dodson, E.J. / Dodson, G.G. / Hodgkin, D. / Isaacs, N.W. / Reynolds, C.D. #2: ジャーナル: Nature / 年: 1976 タイトル: Structure of insulin 4-zinc insulin 著者: Bentley, G. / Dodson, E. / Dodson, G. / Hodgkin, D. / Mercola, D. #3: ジャーナル: Nature / 年: 1989 タイトル: Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer 著者: Derewenda, U. / Derewenda, Z. / Dodson, G. / Reynold, C. / Smith, G. / Sparks, C. / Swenson, D. #4: ジャーナル: J.Biol.Chem. / 年: 2006 タイトル: tpward the active conformation of insulin: stereospecific modelation of a structural swith in the B chain 著者: Hua, Q. / Nakagawa, S. / Hu, S.Q. / Jia, W. / Wang, S. / Weiss, M.A. | ||||||
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 | 3fq9.cif.gz | 52.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb3fq9.ent.gz | 38.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 3fq9.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/fq/3fq9 ftp://data.pdbj.org/pub/pdb/validation_reports/fq/3fq9 | HTTPS FTP |
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-関連構造データ
関連構造データ | 4insS S: 精密化の開始モデル |
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類似構造データ |
-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・ペプチド | 分子量: 2396.739 Da / 分子数: 2 / 変異: A1 is DAL, A8 is DAB / 由来タイプ: 合成 詳細: biosynthetic sequence based on Human Insulin A chain 参照: UniProt: P01308 #2: タンパク質・ペプチド | 分子量: 3433.953 Da / 分子数: 2 / 由来タイプ: 合成 詳細: biosynthetic sequence based on Human Insulin B chain 参照: UniProt: P01308 #3: 化合物 | #4: 水 | ChemComp-HOH / | |
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-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: 1.85 Å3/Da / 溶媒含有率: 33.6 % |
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結晶化 | 温度: 298 K / 手法: 蒸気拡散法 / pH: 7.8 詳細: 0.02M Tris, o.o5M soduim citrate, 5%acetone,0.03% phenol,0.01% zinc acetone, pH 7.8, VAPOR DIFFUSION, temperature 298K |
-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: CHESS / ビームライン: F2 / 波長: 0.948 Å |
検出器 | タイプ: ADSC QUANTUM 210 / 検出器: CCD / 日付: 2001年5月26日 / 詳細: mirrors |
放射 | モノクロメーター: graphite / 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: 0.948 Å / 相対比: 1 |
反射 | 解像度: 1.35→40.92 Å / Num. all: 18393 / Num. obs: 18052 / % possible obs: 98.1 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / 冗長度: 4.1 % / Biso Wilson estimate: 13.7 Å2 / Rmerge(I) obs: 0.039 / Net I/σ(I): 20.2 |
反射 シェル | 解像度: 1.35→1.43 Å / 冗長度: 2.88 % / Rmerge(I) obs: 0.123 / Mean I/σ(I) obs: 9.9 / Num. unique all: 2571 / % possible all: 93 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: 4INS 解像度: 1.35→40.92 Å / Isotropic thermal model: RESTRAINED / 交差検証法: THROUGHOUT / σ(F): 0 / σ(I): 0 / 立体化学のターゲット値: Engh & Huber
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原子変位パラメータ | Biso mean: 18 Å2
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Refine analyze | Luzzati coordinate error obs: 0.16 Å / Luzzati d res low obs: 5 Å / Luzzati sigma a obs: 0.1 Å | |||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 1.35→40.92 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 1.35→1.43 Å / Rfactor Rfree error: 0.015
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