3C1K

Crystal structure of thrombin in complex with inhibitor 15

3C1K の概要

• エントリーDOI: 10.2210/pdb3c1k/pdb
• 分子名称: Prothrombin, Hirugen, 2-{3-[(benzylsulfonyl)amino]-6-methyl-2-oxopyridin-1(2H)-yl}-N-({1-[2-(tert-butylamino)-2-oxoethyl]-4-methyl-1H-imidazol-5-yl}methyl)acetamide, ... (4 entities in total)
• 機能のキーワード: thrombin, thrombin inhibitor complex, acute phase, blood coagulation, cleavage on pair of basic residues, disease mutation, gamma-carboxyglutamic acid, glycoprotein, hydrolase, kringle, protease, secreted, serine protease, zymogen, protease inhibitor, serine protease inhibitor, sulfation, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734; Secreted: P28511
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35114.14

構造登録者

Yan, Y. (登録日: 2008-01-23, 公開日: 2008-03-18, 最終更新日: 2024-11-20)

主引用文献

Isaacs, R.C.,Solinsky, M.G.,Cutrona, K.J.,Newton, C.L.,Naylor-Olsen, A.M.,McMasters, D.R.,Krueger, J.A.,Lewis, S.D.,Lucas, B.J.,Kuo, L.C.,Yan, Y.,Lynch, J.J.,Lyle, E.A.
Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 2: N-acetamidoimidazoles.
Bioorg.Med.Chem.Lett., 18:2062-2066, 2008

PubMed Abstract: Guided by X-ray crystallography of thrombin-inhibitor complexes and molecular modeling, alkylation of the N1 nitrogen of the imidazole P1 ligand of the pyridinoneacetamide thrombin inhibitor 1 with various acetamide moieties furnished inhibitors with significantly improved thrombin potency, trypsin selectivity, functional in vitro anticoagulant potency and in vivo antithrombotic efficacy. In the pyrazinoneacetamide series, oral bioavailability was also improved.

PubMed: 18291642
DOI: 10.1016/j.bmcl.2008.01.098

実験手法

X-RAY DIFFRACTION (1.84 Å)