3D4U

Bovine thrombin-activatable fibrinolysis inhibitor (TAFIa) in complex with tick-derived carboxypeptidase inhibitor.

3D4U の概要

• エントリーDOI: 10.2210/pdb3d4u/pdb
• 関連するPDBエントリー: 1KWM 1ZLI
• 分子名称: Carboxypeptidase B2, Carboxypeptidase inhibitor, ZINC ION, ... (6 entities in total)
• 機能のキーワード: protease-inhibitor complex, carboxypeptidase, glycoprotein, hydrolase, metal-binding, metalloprotease, protease, secreted, zymogen, blood coagulation, fibrinolysis, metalloenzyme inhibitor, metalloprotease inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Rhipicephalus bursa; 詳細
• 細胞内の位置: Secreted (By similarity): Q2KIG3; Secreted: Q5EPH2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44500.68

構造登録者

Sanglas, L.,Valnickova, Z.,Arolas, J.L.,Pallares, I.,Guevara, T.,Sola, M.,Kristensen, T.,Enghild, J.J.,Aviles, F.X.,Gomis-Ruth, F.X. (登録日: 2008-05-15, 公開日: 2008-08-19, 最終更新日: 2024-10-30)

主引用文献

Sanglas, L.,Valnickova, Z.,Arolas, J.L.,Pallares, I.,Guevara, T.,Sola, M.,Kristensen, T.,Enghild, J.J.,Aviles, F.X.,Gomis-Ruth, F.X.
Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis.
Mol.Cell, 31:598-606, 2008

PubMed Abstract: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a metallocarboxypeptidase (MCP) that links blood coagulation and fibrinolysis. TAFI hampers fibrin-clot lysis and is a pharmacological target for the treatment of thrombotic conditions. TAFI is transformed through removal of its prodomain by thrombin-thrombomodulin into TAFIa, which is intrinsically unstable and has a short half-life in vivo. Here we show that purified bovine TAFI activated in the presence of a proteinaceous inhibitor renders a stable enzyme-inhibitor complex. Its crystal structure reveals that TAFIa conforms to the alpha/beta-hydrolase fold of MCPs and displays two unique flexible loops on the molecular surface, accounting for structural instability and susceptibility to proteolysis. In addition, point mutations reported to enhance protein stability in vivo are mainly located in the first loop and in another surface region, which is a potential heparin-binding site. The protein inhibitor contacts both the TAFIa active site and an exosite, thus contributing to high inhibitory efficiency.

PubMed: 18722183
DOI: 10.1016/j.molcel.2008.05.031

実験手法

X-RAY DIFFRACTION (1.7 Å)