The regulation of factor IXa by supersulfated low molecular weight heparin.

ABSTRACT: Supersulfated low molecular weight heparin (ssLMWH) inhibits the intrinsic tenase (factor IXa-factor VIIIa) complex in an antithrombin-independent manner. Recombinant factor IXa with alanine substitutions in the protease domain (K126A, N129A, K132A, R165A, R170A, N178A, R233A) was assessed with regard to heparin affinity in solution and ability to regulate protease activity within the factor IXa-phospholipid (PL) and intrinsic tenase complexes. In a soluble binding assay, factor IXa K126A, K132A, and R233A dramatically (10-20-fold) reduced ssLMWH affinity, while factor IXa N129A and R165A moderately (5-fold) reduced affinity relative to wild type. In the factor IXa-PL complex, binding affinity for ssLMWH was increased 4-fold, and factor X activation was inhibited with a potency 7-fold high

SUBMITTER: Misenheimer TM 

PROVIDER: S-EPMC2996140 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature