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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: 2p3u | ||||||
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タイトル | Crystal structure of human factor XA complexed with 3-chloro-N-(4-chloro-2-{[(5-chloropyridin-2-yl)amino]carbonyl}-6-methoxyphenyl)-4-[(1-methyl-1H-imidazol-2-yl)methyl]thiophene-2-carboxamide {Pfizer 320663} | ||||||
![]() | (Coagulation factor X) x 2 | ||||||
![]() | BLOOD CLOTTING / protein inhibitor complex / 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 leukocyte chemotaxis / 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 ...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 leukocyte chemotaxis / 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. | ||||||
![]() | #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: Discovery of Highly Potent and Orally Available Thiophene-Anthranilamide-Based 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. #3: ![]() タイトル: Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa 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. #4: ![]() タイトル: Structure-activity relationships of substituted benzothiophene-anthranilamide factor Xa inhibitors 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. #5: ![]() タイトル: Preparation, Characterization and the Crystal Structure of the Inhibitor ZK-807834 (Ci-1031) Complexed with Factor Xa 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. #6: ![]() タイトル: Crystal Structures of Human Factor Xa Complexed with Potent Inhibitors 著者: Adler, M. / Davey, D.D. / Phillips, G.B. / Kim, S.H. / Jancarik, J. / Rumennik, G. / Light, D.L. / Whitlow, M. #7: ![]() 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 | ![]() | 80.8 KB | 表示 | ![]() |
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PDB形式 | ![]() | 57.8 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 788.2 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 791.1 KB | 表示 | |
XML形式データ | ![]() | 16.2 KB | 表示 | |
CIF形式データ | ![]() | 23.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-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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詳細 | BIOMOLECULE: 1 THIS ENTRY CONTAINS THE CRYSTALLOGRAPHIC ASYMMETRIC UNIT WHICH CONSISTS OF 2 CHAIN(S). FACTOR XA FORMS A COMPLEX WITH FACTOR VA IN THE PRESENCE OF CALCIUM AND A PHOSPHOLIPID MEMBRANE TO PRODUCE THE PROTHROMBINASE COMPLEX. THIS ENTRY CONTAINS THE EPIDERMAL GROWTH FACTOR LIKE DOMAIN 2(L) AND THE CATALYTIC DOMAIN (A) OF FACTOR XA IN THE CRYSTALLOGRAPHIC ASYMMETRIC UNIT. THE COORDINATES DO NOT CONTAIN THE GLA DOMAIN OR THE EPIDERMAL GROWTH FACTOR LIKE DOMAIN 1 OF FACTOR XA. ALTHOUGH THE ASYMMETRIC UNIT CONTAINS A FUNCTIONAL PROTEASE, IT DOES HAVE THE SAME SPECIFICITY AS THE PROTHROMBINASE COMPLEX. SEE REMARK 350 FOR INFORMATION ON GENERATING THE BIOLOGICAL MOLECULE(S). GENERATING THE BIOMOLECULE COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN. BIOMOLECULE: 1 APPLY THE FOLLOWING TO CHAINS: A, L BIOMT1 1 1.000000 0.000000 0.000000 0.00000 BIOMT2 1 0.000000 1.000000 0.000000 0.00000 BIOMT3 1 0.000000 0.000000 1.000000 0.00000 |
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要素
#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 / 由来: (天然) ![]() | ||||
#3: 化合物 | #4: 化合物 | ChemComp-663 / | #5: 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: 蒸発脱水法 / pH: 7.5 詳細: A THREE-FOLD EXCESS OF 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide WAS ADDED TO THE DES-GLA- ...詳細: A THREE-FOLD EXCESS OF 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide 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. 30-40 UL SITTING DROPS CONTAINING SATURATED INHIBITOR (5 MM) IN 21% PEG1500, 5 MM CACL2, 20 MM NACL, 25 MM TRIS PH 7.5 (CRYSTAL SOAKING SOLUTION) WERE EQUILIBRATED OVER A 1 ML RESERVOIR CONTAINING THE CRYSTAL SOAKING SOLUTION FOR 1 TO 2 DAYS. A SINGLE FACTOR XA CRYSTAL WAS TRANSFERRED USING A MOUNTED CRYOLOOP INTO ONE OF THESE SITTING DROPS AND ALLOWED TO SOAK FOR THREE OR MORE DAYS, EVAPORATION, 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: MAR scanner 345 mm plate / 検出器: IMAGE PLATE / 日付: 2000年3月11日 |
放射 | モノクロメーター: SI(111) / 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: 1.08 Å / 相対比: 1 |
反射 | 解像度: 1.62→20 Å / Num. obs: 40439 / % possible obs: 98.9 % / 冗長度: 3.7 % / Biso Wilson estimate: 21.9 Å2 / Rsym value: 0.04 / Net I/σ(I): 18.4 |
反射 シェル | 解像度: 1.62→1.66 Å / 冗長度: 3.7 % / Mean I/σ(I) obs: 3.2 / Rsym value: 0.392 / % possible all: 97.9 |
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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: OTHER 開始モデル: PDB Entry 1FJS 解像度: 1.62→19.8 Å / Rfactor Rfree error: 0.005 / Data cutoff high absF: 1261609.71 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / 交差検証法: THROUGHOUT / σ(F): 2
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溶媒の処理 | 溶媒モデル: FLAT MODEL / Bsol: 62.2348 Å2 / ksol: 0.38301 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 26.3 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: 1.62→19.8 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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