Dramatic enhancement of the catalytic activity of coagulation factor IXa by alcohols

FEBS Letters

Kopetzki, Erhard¹  Hopfner, Karl-Peter³  Bode, Wolfram³  Stürzebecher, Jörg² 

[1] Boehringer Mannheim GmbH, Werk Penzberg, D-82372 Penzberg, Germany;Zentrum für Vaskuläre Biologie und Medizin Erfurt, Friedrich-Schiller-Universität Jena, Nordhäuser Straße 78, D-99089 Erfurt, Germany;Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany

关键词: Coagulation factor IXa;    Synthetic substrate;    Chromogenic assay;    FVIIIa;    factor VIIIa;    FIXa;    factor IXa;    rFIXa;    recombinant factor IXa;    FXa;    factor Xa;    FXIa;    factor XIa;    FXIIa;    factor XIIa;    MOC;    methoxycarbonyl;    MS;    methylsulfonyl;    HHT;    hexahydrotyrosyl;    CHG;    cyclohexylglycyl;    PEG;    polyethylene glycol;    TF;    tissue factor;   

DOI  :  10.1016/S0014-5793(97)00811-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The coagulation factor IXa (FIXa) exhibits a very weak proteolytic activity towards natural or synthetic substrates. Upon complex formation with its cofactor FVIIIa and Ca²⁺-mediated binding to phospholipid membranes, FIXa becomes a very potent activator of FX. The presence of FVIIIa has no effect on the cleavage of peptide substrates by FIXa, however. We found that several alcohols dramatically enhance the catalytic activity of human FIXa towards synthetic substrates. Substrates with the tripeptidyl moiety R–d-Xxx–Gly–Arg are especially susceptible to the enhanced FIXa catalysis. Maximal increase up to 20-fold has been measured in the presence of ethylene glycol. We suggest that alcohols modify the conformation of FIXa rendering the active-site cleft more easily accessible to tripeptide substrates with a hydrophobic residue in the P3-position.

【 授权许可】

Unknown