English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/104680
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

DC FieldValueLanguage
dc.contributor.authorSanglas, Laura-
dc.contributor.authorValnickova, Zuzana-
dc.contributor.authorArolas, Joan L.-
dc.contributor.authorPallarés, Irantzu-
dc.contributor.authorGuevara, Tibisay-
dc.contributor.authorSolà, Maria-
dc.contributor.authorKristensen, Torsten Nygaard-
dc.contributor.authorEnghild, Jan J.-
dc.contributor.authorAvilés, Francesc X.-
dc.contributor.authorGomis-Rüth, F. Xavier-
dc.date.accessioned2014-11-07T12:01:59Z-
dc.date.available2014-11-07T12:01:59Z-
dc.date.issued2008-08-22-
dc.identifierdoi: 10.1016/j.molcel.2008.05.031-
dc.identifierissn: 1097-2765-
dc.identifier.citationMolecular Cell 31(4): 598-606 (2008)-
dc.identifier.urihttp://hdl.handle.net/10261/104680-
dc.description.abstractThrombin-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 α/β-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. © 2008 Elsevier Inc. All rights reserved.-
dc.description.sponsorshipThis study was supported by the following grants: BIO2007-68046, BIO2006-02668, BFU2006-09593, PSE-010000-2007-1, and the CONSOLIDER-INGENIO 2010 Project “La Factoría de Cristalización” (CSD2006-00015) from Spanish ministries; EU FP6 Strep Project LSHG-CT-2006-018830 “CAMP”; and 2005SGR00280 and 2005SGR01027 from the Generalitat de Catalunya. Additional funding was obtained by J.J.E. from the Danish National Science Research Council. L.S. and I.P. enjoyed Ph.D. fellowships from the Spanish Ministry of Education and Science. M.S. and J.L.A. are, respectively, beneficiaries of the “Ramón y Cajal” and “Juan de la Cierva” Programs of the Spanish Ministry of Education and Science-
dc.publisherCell Press-
dc.relation.isversionofPostprint-
dc.rightsopenAccess-
dc.subjecthydrolase-
dc.subjectProtein-
dc.subjectThrombin activatable fibrinolysis inhibitor-
dc.titleStructure of Activated Thrombin-Activatable Fibrinolysis Inhibitor, a Molecular Link between Coagulation and Fibrinolysis-
dc.typeartículo-
dc.identifier.doi10.1016/j.molcel.2008.05.031-
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.molcel.2008.05.031-
dc.date.updated2014-11-07T12:01:59Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
Appears in Collections:(IBMB) Artículos
Files in This Item:
File Description SizeFormat 
Sanglas_TAFITCI_9rr.doc281,5 kBMicrosoft WordView/Open
Show simple item record
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.