The influence of sodium ion binding on factor IXa activity.
Sodium plays an important role in modulating both the amidolytic and proteolytic activities of thrombin. By contrast, while the optimal amidolytic activity of factor Xa requires Na(+), the proteolytic activity of factor Xa in the prothrombinase complex is minimally affected by the monovalent cation. In this study, we analyzed the effect of Na(+) on the amidolytic and proteolytic activity of factor IXa in the absence and presence of factor VIIIa. Factor IXa exhibited normal activity towards a fIXa-specific chromogenic substrate and antithrombin in the presence of physiological concentrations of Ca(2+) with no obvious requirement for Na(+) in either reaction. Further studies revealed that factor IXa binds to its cofactor factor VIIIa with a normal affinity in the absence of Na(+) and that the catalytic function in the intrinsic Xase complex is also independent of Na(+) in the presence of physiological concentrations of Ca(2+). These results suggest that unlike the important role that Na(+) plays in modulating the macromolecular substrate specificity of thrombin, the monovalent cation is not required for the physiological function of factor Ixa in the intrinsic Xase complex.
Gopalakrishna
Kota
K
Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, 1402 S. Grand Blvd., MO 63104, USA.
Rezaie
Alireza R
AR
D000494:Allosteric Regulation; D000991:Antithrombins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001779:Blood Coagulation Factors / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002863:Chromogenic Compounds; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D015949:Factor IXa / Q000737:chemistry* / Q000378:metabolism; D015944:Factor VIIIa / Q000737:chemistry / Q000378:metabolism; D005170:Factor X / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides; D011485:Protein Binding; D012964:Sodium / Q000737:chemistry* / Q000378:metabolism
D000991:Antithrombins; D001779:Blood Coagulation Factors; D002863:Chromogenic Compounds; D009363:Neoplasm Proteins; D009842:Oligopeptides; D015944:Factor VIIIa; C035205:methylsulfonylleucyl-glycyl-arginine-4-nitroanilide; D005170:Factor X; D012964:Sodium; D015949:Factor IXa; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant; D002118:Calcium