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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: 2p3t | ||||||
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タイトル | Crystal structure of human factor XA complexed with 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide | ||||||
![]() | (Coagulation factor ...) x 2 | ||||||
![]() | BLOOD CLOTTING / protein inhibitor complex / nonamidine / coagulation cofactor / protease | ||||||
機能・相同性 | ![]() coagulation factor Xa / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / Extrinsic Pathway of Fibrin Clot Formation / positive regulation of TOR signaling / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins ...coagulation factor Xa / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / Extrinsic Pathway of Fibrin Clot Formation / positive regulation of TOR signaling / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / Intrinsic Pathway of Fibrin Clot Formation / phospholipid binding / Golgi lumen / blood coagulation / positive regulation of cell migration / endoplasmic reticulum lumen / external side of plasma membrane / serine-type endopeptidase activity / calcium ion binding / proteolysis / extracellular space / extracellular region / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | ![]() ![]() | ||||||
![]() | Adler, M. / Whitlow, M. | ||||||
![]() | ![]() タイトル: Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors. 著者: Ye, B. / Arnaiz, D.O. / Chou, Y.L. / Griedel, B.D. / Karanjawala, R. / Lee, W. / Morrissey, M.M. / Sacchi, K.L. / Sakata, S.T. / Shaw, K.J. / Wu, S.C. / Zhao, Z. / Adler, M. / Cheeseman, S. / ...著者: Ye, B. / Arnaiz, D.O. / Chou, Y.L. / Griedel, B.D. / Karanjawala, R. / Lee, W. / Morrissey, M.M. / Sacchi, K.L. / Sakata, S.T. / Shaw, K.J. / Wu, S.C. / Zhao, Z. / Adler, M. / Cheeseman, S. / Dole, W.P. / Ewing, J. / Fitch, R. / Lentz, D. / Liang, A. / Light, D. / Morser, J. / Post, J. / Rumennik, G. / Subramanyam, B. / Sullivan, M.E. / Vergona, R. / Walters, J. / Wang, Y.X. / White, K.A. / Whitlow, M. / Kochanny, M.J. #1: ![]() タイトル: Crystal Structures of Two Potent Nonamidine Inhibitors Bound to Factor Xa 著者: Adler, M. / Kochanny, M.J. / Bin, Y. / Rumennik, G. / Light, D.L. / Biancalana, S. / Whitlow, M. #2: ![]() タイトル: Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa 著者: Kochanny, M.J. / Adler, M. / Ewing, J. / Griedel, B.D. / Ho, E. / Karanjawala, R. / Lee, W. / Lentz, D. / Liang, A.M. / Morrissey, M.M. / Phillips, G.B. / Post, J. / Sakata, K.L. / ...著者: Kochanny, M.J. / Adler, M. / Ewing, J. / Griedel, B.D. / Ho, E. / Karanjawala, R. / Lee, W. / Lentz, D. / Liang, A.M. / Morrissey, M.M. / Phillips, G.B. / Post, J. / Sakata, K.L. / Subramanyam, B. / Vergona, R. / Walters, J. / White, K.A. / Whitlow, M. / Ye, B. / Zhao, Z. / Shaw, K.J. #3: ![]() タイトル: Structure-activity relationships of substituted benzothiophene-anthranilamide factor Xa inhibitors 著者: Chou, Y.L. / Davey, D.D. / Eagen, K.A. / Griedel, B.D. / Karanjawala, R. / Phillips, G.B. / Sacchi, K.L. / Shaw, K.J. / Wu, S.C. / Lentz, D. / Liang, A.M. / Trinh, L. / Morrissey, M.M. / Kochanny, M.J. #4: ![]() タイトル: Preparation, Characterization and the Crystal Structure of the Inhibitor ZK-807834 (Ci-1031) Complexed with Factor Xa 著者: Adler, M. / Davey, D.D. / Phillips, G.B. / Kim, S.H. / Jancarik, J. / Rumennik, G. / Light, D.L. / Whitlow, M. #5: ![]() タイトル: Crystal Structures of Human Factor Xa Complexed with Potent Inhibitors 著者: Maignan, S. / Guilloteau, J.P. / Pouzieux, S. / Choi-Sledeski, Y.M. / Becker, M.R. / Klein, S.I. / Ewing, W.R. / Pauls, H.W. / Spada, A.P. / Mikol, V. #6: ![]() タイトル: Discovery of N-[2-[5-[Amino(Imino)Methyl]-2-Hydroxyphenoxy]-3,5-Difluoro- 6-[3-(4,5-Dihydro-1-Methyl-1H-Imidazol-2-Yl)Phenoxy]Pyridin-4-Yl]-N-Methylglycine (Zk-807834): A Potent, ...タイトル: Discovery of N-[2-[5-[Amino(Imino)Methyl]-2-Hydroxyphenoxy]-3,5-Difluoro- 6-[3-(4,5-Dihydro-1-Methyl-1H-Imidazol-2-Yl)Phenoxy]Pyridin-4-Yl]-N-Methylglycine (Zk-807834): A Potent, Selective, and Orally Active Inhibitor of the Blood Coagulation Enzyme Factor Xa 著者: Phillips, G.B. / Buckman, B.O. / Davey, D.D. / Eagen, K.A. / Guilford, W.J. / Hinchman, J. / Ho, E. / Koovakkat, S. / Liang, A.M. / Light, D.R. / Mohan, R. / Ng, H.P. / Post, J.M. / Shaw, K.J. ...著者: Phillips, G.B. / Buckman, B.O. / Davey, D.D. / Eagen, K.A. / Guilford, W.J. / Hinchman, J. / Ho, E. / Koovakkat, S. / Liang, A.M. / Light, D.R. / Mohan, R. / Ng, H.P. / Post, J.M. / Shaw, K.J. / Smith, D. / Subramanyam, B. / Sullivan, M.E. / Trinh, L. / Vergona, R. / Walters, J. / White, K. / Whitlow, M. / Wu, S. / Xu, W. / Morrissey, M.M. | ||||||
履歴 |
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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 | ![]() | 77.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 55.5 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
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 | ![]() 1fjsS 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
-Coagulation factor ... , 2種, 2分子 AB
#1: タンパク質 | 分子量: 5589.234 Da / 分子数: 1 / 断片: EGF-like 2 domain / 由来タイプ: 天然 / 詳細: EXTRACTED FROM BLOOD / 由来: (天然) ![]() |
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#2: タンパク質 | 分子量: 26346.000 Da / 分子数: 1 / 断片: CATALYTIC DOMAIN / 由来タイプ: 天然 / 詳細: EXTRACTED FROM BLOOD / 由来: (天然) ![]() |
-非ポリマー , 4種, 175分子 ![](data/chem/img/CA.gif)
![](data/chem/img/CL.gif)
![](data/chem/img/993.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/CL.gif)
![](data/chem/img/993.gif)
![](data/chem/img/HOH.gif)
#3: 化合物 | ChemComp-CA / |
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#4: 化合物 | ChemComp-CL / |
#5: 化合物 | ChemComp-993 / |
#6: 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: 2.44 Å3/Da / 溶媒含有率: 51.2 % |
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結晶化 | 温度: 295 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 7.5 詳細: A three-fold excess of the inhibitor was added to the DES-GLA-FACTOR XA. the protein was then concentrated to 12-17 MG/ML. Crystals were grown using 2 UL of complex with 2 UL of reservoir ...詳細: A three-fold excess of the inhibitor was added to the DES-GLA-FACTOR XA. the protein was then concentrated to 12-17 MG/ML. Crystals were grown using 2 UL of complex with 2 UL of reservoir containing 15-21% PEG1500 and 10 MM CACL2, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 295K |
-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: ADSC QUANTUM 4 / 検出器: CCD / 日付: 2000年2月24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: 1.0332 Å / 相対比: 1 |
反射 | 解像度: 1.92→50 Å / Num. obs: 25286 / % possible obs: 99.2 % / Observed criterion σ(I): -3 / 冗長度: 3.52 % / Biso Wilson estimate: 15 Å2 / Rsym value: 0.0749 / Net I/σ(I): 9.17 |
反射 シェル | 解像度: 1.92→2.04 Å / 冗長度: 3.57 % / Mean I/σ(I) obs: 1.76 / Rsym value: 0.3341 / % possible all: 100 |
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解析
ソフトウェア |
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精密化 | 開始モデル: PDB Entry 1FJS 解像度: 1.92→19.88 Å / Rfactor Rfree error: 0.007 / Data cutoff high absF: 171365.35 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / 交差検証法: THROUGHOUT / σ(F): 2 / 立体化学のターゲット値: Engh & Huber
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溶媒の処理 | 溶媒モデル: FLAT MODEL / Bsol: 54.0173 Å2 / ksol: 0.358387 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 28.1 Å2
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Refine analyze |
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精密化ステップ | サイクル: LAST / 解像度: 1.92→19.88 Å
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拘束条件 |
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LS精密化 シェル | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 6
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Xplor file |
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