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An antithrombin III variant (GST-II/rAT) with normal anti-IIa and anti-Xa activity, but a significantly reduced anti-IIa and increased anti-Xa activity, was constructed by the site-directed mutagenesis of the alpha-Cys39 residue of wild-type GST-I. The variant (rAT) has increased biological half-life and resistance to heparin-induced inhibition and prolonged anticoagulant effects in healthy volunteers. The work highlights the importance of the N-terminal residues in the enzymatic/anticoagulant properties of rAT, and proposes an important role for alpha-Cys39 in maintaining the integrity and the biological properties of the heparin-induced inhibition site of AT. The replacement of alpha-Cys39 with Ser in wild-type GST-I by site-directed mutagenesis yielded a recombinant antithrombin III with reduced anti-IIa and increased anti-Xa activity, prolonged biological half-life and resistance to heparin-induced inhibition and prolonged anticoagulant effects in healthy volunteers.Q:
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