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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: 6gl8 | ||||||
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タイトル | Crystal structure of Bcl-2 in complex with the novel orally active inhibitor S55746 | ||||||
![]() | Apoptosis regulator Bcl-2,Apoptosis regulator Bcl-2,Apoptosis regulator Bcl-2,Bcl-2-like protein 1,Apoptosis regulator Bcl-2,Apoptosis regulator Bcl-2,Apoptosis regulator Bcl-2 | ||||||
![]() | APOPTOSIS / APOPTOSIS-INHIBITOR COMPLEX / BCL-2 / BH3-mimetics | ||||||
機能・相同性 | ![]() channel inhibitor activity / negative regulation of cellular pH reduction / negative regulation of retinal cell programmed cell death / pigment granule organization / CD8-positive, alpha-beta T cell lineage commitment / BAD-BCL-2 complex / positive regulation of skeletal muscle fiber development / regulation of glycoprotein biosynthetic process / positive regulation of melanocyte differentiation / melanin metabolic process ...channel inhibitor activity / negative regulation of cellular pH reduction / negative regulation of retinal cell programmed cell death / pigment granule organization / CD8-positive, alpha-beta T cell lineage commitment / BAD-BCL-2 complex / positive regulation of skeletal muscle fiber development / regulation of glycoprotein biosynthetic process / positive regulation of melanocyte differentiation / melanin metabolic process / myeloid cell apoptotic process / cochlear nucleus development / osteoblast proliferation / mesenchymal cell development / retinal cell programmed cell death / positive regulation of neuron maturation / negative regulation of osteoblast proliferation / gland morphogenesis / renal system process / regulation of cell-matrix adhesion / The NLRP1 inflammasome / dendritic cell apoptotic process / ear development / negative regulation of calcium ion transport into cytosol / stem cell development / lymphoid progenitor cell differentiation / T cell apoptotic process / melanocyte differentiation / negative regulation of myeloid cell apoptotic process / negative regulation of epithelial cell apoptotic process / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / negative regulation of dendritic cell apoptotic process / negative regulation of T cell apoptotic process / B cell apoptotic process / glomerulus development / regulation of nitrogen utilization / positive regulation of multicellular organism growth / metanephros development / focal adhesion assembly / neuron maturation / Regulation of MITF-M-dependent genes involved in apoptosis / negative regulation of motor neuron apoptotic process / regulation of viral genome replication / oocyte development / endoplasmic reticulum calcium ion homeostasis / regulation of mitochondrial membrane permeability / response to UV-B / calcium ion transport into cytosol / response to iron ion / negative regulation of ossification / motor neuron apoptotic process / negative regulation of mitochondrial depolarization / axon regeneration / epithelial cell apoptotic process / smooth muscle cell migration / NFE2L2 regulating tumorigenic genes / intrinsic apoptotic signaling pathway in response to oxidative stress / organ growth / negative regulation of B cell apoptotic process / hair follicle morphogenesis / branching involved in ureteric bud morphogenesis / digestive tract morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / B cell lineage commitment / positive regulation of smooth muscle cell migration / negative regulation of G1/S transition of mitotic cell cycle / pore complex / negative regulation of intrinsic apoptotic signaling pathway / T cell homeostasis / BH3 domain binding / B cell homeostasis / humoral immune response / B cell proliferation / negative regulation of apoptotic signaling pathway / negative regulation of anoikis / regulation of calcium ion transport / extrinsic apoptotic signaling pathway via death domain receptors / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / Activation of BAD and translocation to mitochondria / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / hematopoietic stem cell differentiation / behavioral fear response / response to glucocorticoid / cellular response to glucose starvation / ovarian follicle development / skeletal muscle fiber development / extrinsic apoptotic signaling pathway in absence of ligand / spleen development / homeostasis of number of cells within a tissue / positive regulation of B cell proliferation / response to cytokine / negative regulation of autophagy / regulation of transmembrane transporter activity / reactive oxygen species metabolic process / axonogenesis / ossification / release of cytochrome c from mitochondria / negative regulation of cell migration / regulation of mitochondrial membrane potential 類似検索 - 分子機能 | ||||||
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手法 | ![]() ![]() ![]() | ||||||
![]() | Casara, P. / Davidson, J. / Claperon, A. / Le Toumelin-Braizat, G. / Vogler, M. / Bruno, A. / Chanrion, M. / Lysiak-Auvity, G. / Le Diguarher, T. / Starck, J.B. ...Casara, P. / Davidson, J. / Claperon, A. / Le Toumelin-Braizat, G. / Vogler, M. / Bruno, A. / Chanrion, M. / Lysiak-Auvity, G. / Le Diguarher, T. / Starck, J.B. / Chen, I. / Whitehead, N. / Graham, C. / Matassova, N. / Dokurno, P. / Pedder, C. / Wang, Y. / Qiu, S. / Girard, A.M. / Schneider, E. / Grave, F. / Studeny, A. / Guasconi, G. / Rocchetti, F. / Maiga, S. / Henlin, J.M. / Colland, F. / Kraus-Berthier, L. / Le Gouill, S. / Dyer, M.J.S. / Hubbard, R. / Wood, M. / Amiot, M. / Cohen, G.M. / Hickman, J.A. / Morris, E. / Murray, J. / Geneste, O. | ||||||
![]() | ![]() タイトル: S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth. 著者: Casara, P. / Davidson, J. / Claperon, A. / Le Toumelin-Braizat, G. / Vogler, M. / Bruno, A. / Chanrion, M. / Lysiak-Auvity, G. / Le Diguarher, T. / Starck, J.B. / Chen, I. / Whitehead, N. / ...著者: Casara, P. / Davidson, J. / Claperon, A. / Le Toumelin-Braizat, G. / Vogler, M. / Bruno, A. / Chanrion, M. / Lysiak-Auvity, G. / Le Diguarher, T. / Starck, J.B. / Chen, I. / Whitehead, N. / Graham, C. / Matassova, N. / Dokurno, P. / Pedder, C. / Wang, Y. / Qiu, S. / Girard, A.M. / Schneider, E. / Grave, F. / Studeny, A. / Guasconi, G. / Rocchetti, F. / Maiga, S. / Henlin, J.M. / Colland, F. / Kraus-Berthier, L. / Le Gouill, S. / Dyer, M.J.S. / Hubbard, R. / Wood, M. / Amiot, M. / Cohen, G.M. / Hickman, J.A. / Morris, E. / Murray, J. / Geneste, O. | ||||||
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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 | ![]() | 51.5 KB | 表示 | ![]() |
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PDB形式 | ![]() | 34.8 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
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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 | ![]() 2w3lS 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: 20236.555 Da / 分子数: 1 変異: L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, ...変異: L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E,L95K, Q99E 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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#2: 化合物 | ChemComp-F3Q / ~{ |
#3: 水 | ChemComp-HOH / |
-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: 1.76 Å3/Da / 溶媒含有率: 29.7 % |
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結晶化 | 温度: 284 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 5.25 詳細: 0.1 M sodium acetate buffer pH 5.25, 20% Jeffamine600, 10% PEG3350 |
-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: ![]() ![]() ![]() |
検出器 | タイプ: DECTRIS PILATUS3 S 6M / 検出器: PIXEL / 日付: 2016年11月23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: 0.97857 Å / 相対比: 1 |
反射 | 解像度: 1.39→42.5 Å / Num. obs: 28969 / % possible obs: 98.9 % / 冗長度: 4.2 % / CC1/2: 0.999 / Rmerge(I) obs: 0.034 / Rpim(I) all: 0.019 / Rrim(I) all: 0.039 / Net I/σ(I): 19.5 |
反射 シェル | 解像度: 1.39→1.42 Å / 冗長度: 3.7 % / Rmerge(I) obs: 0.54 / Mean I/σ(I) obs: 2.2 / Num. unique obs: 1967 / CC1/2: 0.877 / Rpim(I) all: 0.31 / Rrim(I) all: 0.63 / % possible all: 91.7 |
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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: 2W3L 解像度: 1.4→20 Å / Cor.coef. Fo:Fc: 0.97 / Cor.coef. Fo:Fc free: 0.966 / SU B: 1.12 / SU ML: 0.044 / 交差検証法: THROUGHOUT / ESU R: 0.066 / ESU R Free: 0.064 / 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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 mean: 23.1 Å2
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精密化ステップ | サイクル: 1 / 解像度: 1.4→20 Å
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拘束条件 |
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