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http://purl.uniprot.org/citations/15545266http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15545266http://www.w3.org/2000/01/rdf-schema#comment"Thrombosis can lead to life-threatening conditions such as acute myocardial infarction, pulmonary embolism, and stroke. Although commonly used anti-coagulant drugs, such as low molecular weight heparin and warfarin, are effective, they carry a significant risk of inducing severe bleeding complications, and there is a need for safer drugs. Activated Factor XI (FXIa) is a key enzyme in the amplification phase of the coagulation cascade. Anti-human FXI antibody significantly reduces thrombus growth in a baboon thrombosis model without bleeding problems (Gruber, A., and Hanson, S. R. (2003) Blood 102, 953-955). Therefore, FXIa is a potential target for anti-thrombosis therapy. To determine the structure of FXIa, we derived a recombinant catalytic domain of FXI, consisting of residues 370-607 (rhFXI370-607). Here we report the first crystal structure of rhFXI370-607 in complex with a substitution mutant of ecotin, a panserine protease protein inhibitor secreted by Escherichia coli, to 2.2 A resolution. The presence of ecotin not only assisted in the crystallization of the enzyme but also revealed unique structural features in the active site of FXIa. Subsequently, the sequence from P5 to P2' in ecotin was mutated to the FXIa substrate sequence, and the structures of the rhFXI370-607-ecotin mutant complexes were determined. These structures provide us with an understanding of substrate binding interactions of FXIa, the structural information essential for the structure-based design of FXIa-selective inhibitors."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m411309200"xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Jin L."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Abdel-Meguid S.S."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Strickler J.E."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Pandey P."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Gorga J.C."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Weaver D.T."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Seidl K.J."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Babine R.E."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/author"Gelfand E."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/pages"4704-4712"xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/title"Crystal structures of the FXIa catalytic domain in complex with ecotin mutants reveal substrate-like interactions."xsd:string
http://purl.uniprot.org/citations/15545266http://purl.uniprot.org/core/volume"280"xsd:string
http://purl.uniprot.org/citations/15545266http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15545266
http://purl.uniprot.org/citations/15545266http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15545266
http://purl.uniprot.org/uniprot/#_P23827-mappedCitation-15545266http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15545266
http://purl.uniprot.org/uniprot/#_P03951-mappedCitation-15545266http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15545266
http://purl.uniprot.org/uniprot/P23827http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15545266
http://purl.uniprot.org/uniprot/P03951http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15545266