3d4u is a 2 chain structure with sequence from Bos taurus and Rhibu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[CBPB2_BOVIN] Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis.,Sanglas L, Valnickova Z, Arolas JL, Pallares I, Guevara T, Sola M, Kristensen T, Enghild JJ, Aviles FX, Gomis-Ruth FX Mol Cell. 2008 Aug 22;31(4):598-606. PMID:18722183[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Sanglas L, Valnickova Z, Arolas JL, Pallares I, Guevara T, Sola M, Kristensen T, Enghild JJ, Aviles FX, Gomis-Ruth FX. Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis. Mol Cell. 2008 Aug 22;31(4):598-606. PMID:18722183 doi:10.1016/j.molcel.2008.05.031
