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Titolo:
Inhibitory properties of human recombinant Arg(24)-> Gln type-2 tissue factor pathway inhibitor (R24Q TFPI-2)
Autore:
Kamei, S; Petersen, LC; Sprecher, CA; Foster, DC; Kisiel, W;
Indirizzi:
Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA Univ New Mexico Albuquerque NM USA 87131 athol, Albuquerque, NM 87131 USA Novo Nordisk AS, Hlth Care Discovery, Maaloev, Denmark Novo Nordisk AS Maaloev Denmark , Hlth Care Discovery, Maaloev, Denmark Zymogenet Inc, Seattle, WA 98105 USA Zymogenet Inc Seattle WA USA 98105Zymogenet Inc, Seattle, WA 98105 USA
Titolo Testata:
THROMBOSIS RESEARCH
fascicolo: 3, volume: 94, anno: 1999,
pagine: 147 - 152
SICI:
0049-3848(19990501)94:3<147:IPOHRA>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEINASE-INHIBITORS; CDNA CLONING; FACTOR-VIIA; EXPRESSION; SEQUENCE; GENE;
Keywords:
tissue factor pathway inhibitor-2; Kunitz-type proteinase inhibitor; placental protein 5; mutagenesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
17
Recensione:
Indirizzi per estratti:
Indirizzo: Kisiel, W Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USAUniv New Mexico Albuquerque NM USA 87131 uquerque, NM 87131 USA
Citazione:
S. Kamei et al., "Inhibitory properties of human recombinant Arg(24)-> Gln type-2 tissue factor pathway inhibitor (R24Q TFPI-2)", THROMB RES, 94(3), 1999, pp. 147-152

Abstract

Human type-2 tissue factor pathway inhibitor (TFPI-2), also known as placental protein 5, is a 32-kDa serine proteinase inhibitor consisting of threetandemly arranged Kunitz-type domains homologous to tissue factor pathway inhibitor. TFPI-2 inhibits a variety of serine proteinases involved in coagulation and fibrinolysis through an arginine residue (R24) in its first Kunitz-type domain, which constitutes a putative P-1 residue for the substraterecognition sites of these proteinases. As recent studies have shown that this P-1 residue to be a glutamine in murine TFPI-2, we constructed, expressed, and purified a human TFPI-2 mutant with glutamine substituted for arginine at position 24 (R24Q TFPI-2), R24Q TFPI-2 lost similar to 90% of its inhibitory activity towards bovine trypsin and virtually all inhibitory activity towards human plasmin and the factor VIIa-tissue factor complex, emphasizing the importance of the P-1 Arg(24) residue in the inhibition of theseserine proteinases. However, whereas wild-type TFPI-2 is a relatively weakinhibitor of human factor Xa amidolytic activity (IC(50)similar to 1 mu M), R24Q TFPI-2 exhibited enhanced inhibitory activity towards the amidolyticand coagulant activities of this proteinase with a K-i of 18 nM. While themolecular basis for the enhanced inhibition of human factor Xa by R24Q TFPI-2 is unknown, these data provide suggestive evidence that murine TFPI-2 may function as a serine proteinase inhibitor in spite of the absence of a P-1 Arg or Lys residue. (C) 1999 Elsevier Science Ltd. All rights reserved.

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Documento generato il 05/12/20 alle ore 01:25:48