3UTU

High affinity inhibitor of human thrombin

3UTU の概要

• エントリーDOI: 10.2210/pdb3utu/pdb
• 関連するPDBエントリー: 2zfo 2ziq 3dt0 3dux 3eqo 3f68
• 分子名称: Thrombin light chain, Thrombin heavy chain, Hirudin variant-1, ... (6 entities in total)
• 機能のキーワード: serine protease, blood clotting, fibrinopeptide a, 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 P00734; Secreted: P01050
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 36023.36

構造登録者

Baum, B.,Steinmetzer, T.,Heine, A.,Klebe, G. (登録日: 2011-11-26, 公開日: 2012-08-29, 最終更新日: 2024-11-20)

主引用文献

Steinmetzer, T.,Baum, B.,Biela, A.,Klebe, G.,Nowak, G.,Bucha, E.
Beyond heparinization: design of highly potent thrombin inhibitors suitable for surface coupling
Chemmedchem, 7:1965-1973, 2012

PubMed Abstract: During extracorporeal circulation, when blood comes in contact with artificial surfaces, patients receive a standard treatment with anticoagulants to avoid blood coagulation. Dialysis patients in particular are systemically treated with heparin up to four times a week, causing a high burden for the body. For potential anticoagulant modification of external materials, such as dialysis equipment, a series of highly potent thrombin inhibitors was developed. All inhibitors share the general formula arylsulfonyl-P3-Pro-4-amidinobenzylamide, where P3 is glycyl or a trifunctional amino acid residue in L-configuration. Among this series, several derivatives inhibit thrombin with Ki values of less than 1 nM. Specificity measurements revealed that this inhibitor type is highly specific for thrombin with negligible activity against related trypsin-like serine proteases. X-ray analysis of the most potent analogue in complex with thrombin demonstrated that the N-terminal arylsulfonyl group occupies the aryl binding site, whereas the P3 side chain is directed into the solvent and therefore is well suited for further coupling. Based on their in vitro profile, these inhibitors are suitable candidates for the development of hemocompatible materials with anticoagulant properties.

PubMed: 22907907
DOI: 10.1002/cmdc.201200292

実験手法

X-RAY DIFFRACTION (1.55 Å)