pubmed-article:11986214 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0020792 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0036098 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0040048 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0015518 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0040203 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0164707 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0439855 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0015505 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0015520 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
pubmed-article:11986214 | lifeskim:mentions | umls-concept:C0282510 | lld:lifeskim |
pubmed-article:11986214 | pubmed:issue | 10 | lld:pubmed |
pubmed-article:11986214 | pubmed:dateCreated | 2002-5-2 | lld:pubmed |
pubmed-article:11986214 | pubmed:abstractText | Saliva of the hard tick and Lyme disease vector, Ixodes scapularis, has a repertoire of compounds that counteract host defenses. Following sequencing of an I scapularis salivary gland complementary DNA (cDNA) library, a clone with sequence homology to tissue factor pathway inhibitor (TFPI) was identified. This cDNA codes for a mature protein, herein called Ixolaris, with 140 amino acids containing 10 cysteines and 2 Kunitz-like domains. Recombinant Ixolaris was expressed in insect cells and shown to inhibit factor VIIa (FVIIa)/tissue factor (TF)-induced factor X (FX) activation with an inhibitory concentration of 50% (IC(50)) in the picomolar range. In nondenaturing gel, Ixolaris interacted stoichiometrically with FX and FXa but not FVIIa. Ixolaris behaves as a fast-and-tight ligand of the exosites of FXa and gamma-carboxyglutamic acid domainless FXa (des-Gla-FXa), increasing its amidolytic activity. At high concentration, Ixolaris attenuates the amidolytic activity of FVIIa/TF; however, in the presence of DEGR-FX or DEGR-FXa (but not des-Gla-DEGR-FXa), Ixolaris becomes a tight inhibitor of FVIIa/TF as assessed by recombinant factor IX (BeneFIX) activation assays. This indicates that FX and FXa are scaffolds for Ixolaris in the inhibition of FVIIa/TF and implies that the Gla domain is necessary for FVIIa/TF/Ixolaris/FX(a) complex formation. Additionally, we show that Ixolaris blocks FXa generation by endothelial cells expressing TF. Ixolaris may be a useful tool to study the structural features of FVIIa, FX, and FXa, and an alternative anticoagulant in cardiovascular diseases. | lld:pubmed |
pubmed-article:11986214 | pubmed:language | eng | lld:pubmed |
pubmed-article:11986214 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:11986214 | pubmed:citationSubset | AIM | lld:pubmed |
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pubmed-article:11986214 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:11986214 | pubmed:month | May | lld:pubmed |
pubmed-article:11986214 | pubmed:issn | 0006-4971 | lld:pubmed |
pubmed-article:11986214 | pubmed:author | pubmed-author:Francischetti... | lld:pubmed |
pubmed-article:11986214 | pubmed:author | pubmed-author:AndersenJohn... | lld:pubmed |
pubmed-article:11986214 | pubmed:author | pubmed-author:RibeiroJosé... | lld:pubmed |
pubmed-article:11986214 | pubmed:author | pubmed-author:ValenzuelaJes... | lld:pubmed |
pubmed-article:11986214 | pubmed:author | pubmed-author:MatherThomas... | lld:pubmed |
pubmed-article:11986214 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:11986214 | pubmed:day | 15 | lld:pubmed |
pubmed-article:11986214 | pubmed:volume | 99 | lld:pubmed |
pubmed-article:11986214 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:11986214 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:11986214 | pubmed:pagination | 3602-12 | lld:pubmed |
pubmed-article:11986214 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
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pubmed-article:11986214 | pubmed:meshHeading | pubmed-meshheading:11986214... | lld:pubmed |
pubmed-article:11986214 | pubmed:year | 2002 | lld:pubmed |
pubmed-article:11986214 | pubmed:articleTitle | Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffolds for the inhibition of factor VIIa/tissue factor complex. | lld:pubmed |
pubmed-article:11986214 | pubmed:affiliation | Section of Medical Entomology, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. | lld:pubmed |
pubmed-article:11986214 | pubmed:publicationType | Journal Article | lld:pubmed |
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