Effect of heparin on the glia-derived-nexin-thrombin interaction.
In order to determine the specificity of the interaction between thrombin and glia-derived nexin (GdN), the inactivation of proteolytically modified human thrombin species by GdN has been studied. The second-order rate constants for the inactivation of alpha-, beta T-, gamma T- and epsilon-thrombin by GdN were 1.41, 0.63, 0.33 and 1.91 microM-1.s-1 respectively. The kinetic properties of gdN were also investigated in the presence of different types of heparin, fractionated according to antithrombin III-binding affinity. Association rate constants of both gdN and antithrombin III with alpha-thrombin were obtained using unfractionated, low- and high-affinity heparin types. The different heparin types gave optimal rates of inhibition at similar heparin concentrations for both inhibitors. At optimal heparin concentrations, the rate of inactivation of alpha-thrombin by GdN was 0.5-1.2 nM-1.s-1, which suggests that, under these conditions, the interaction is diffusion-controlled.
Wallace
A
A
Friedrich Miescher-Institut, Basel, Switzerland.
Rovelli
G
G
Hofsteenge
J
J
Stone
S R
SR
D016564:Amyloid beta-Protein Precursor; D000990:Antithrombin III / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin