title: Structure-function relationships in thrombin-activatable fibrinolysis inhibitor.
abstract: Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator in the balance of coagulation and fibrinolysis. TAFI is a metallocarboxypeptidase that circulates in plasma as zymogen. Activated TAFI (TAFIa) cleaves C-terminal lysine or arginine residues from peptide substrates. The removal of C-terminal lysine residues from partially degraded fibrin leads to reduced plasmin formation and thus attenuation of fibrinolysis. TAFI also plays a role in inflammatory processes via the removal of C-terminal arginine or lysine residues from bradykinin, thrombin-cleaved osteopontin, C3a, C5a and chemerin. TAFI has been studied extensively over the past three decades and recent publications provide a wealth of information, including crystal structures, mutants and structural data obtained with antibodies and peptides. In this review, we combined and compared available data on structure/function relationships of TAFI.
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Plug
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands.
authors.forename: J C M
authors.identifier: http://orcid.org/0000-0002-4198-6780
authors.initials: JC
authors.lastname: Meijers
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D001120:Arginine / Q000737:chemistry; D001777:Blood Coagulation; D001920:Bradykinin / Q000737:chemistry; D025901:Carboxypeptidase B2 / Q000378:metabolism*; D002384:Catalysis; D002417:Cattle; D018925:Chemokines / Q000737:chemistry; D015926:Complement C3a / Q000737:chemistry; D015936:Complement C5a / Q000737:chemistry; D018360:Crystallography, X-Ray; D004792:Enzyme Precursors / Q000737:chemistry; D005342:Fibrinolysis; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D051379:Mice; D009154:Mutation; D053495:Osteopontin / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D000072417:Protein Domains; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013917:Thrombin / Q000737:chemistry
chemical_list: D000906:Antibodies; D018925:Chemokines; D004792:Enzyme Precursors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C478630:RARRES2 protein, human; D053495:Osteopontin; D015926:Complement C3a; D015936:Complement C5a; D001120:Arginine; C585364:CPB2 protein, human; D025901:Carboxypeptidase B2; D013917:Thrombin; D008239:Lysine; D001920:Bradykinin
keywords: carboxypeptidase B2; carboxypeptidase R; carboxypeptidase U; fibrinolysis; thrombin-activatable fibrinolysis inhibitor (TAFI)