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Human thrombin variable region 1, including E39, is involved in interactions with alpha 1-antitrypsin M358R and
P Gaussem1, V Picard, G Chadeuf
1INSERM U.428, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, France.
Abstract:
We used an antithrombin autoantibody (IgG D), the epitope of which encompasses ABE1 and amino acids located within variable region 1, to study thrombin interactions with R358 alpha 1-AT and protein C. IgG D inhibited the thrombin interaction with R358 alpha 1-AT, while hirugen had no effect, indicating that the interaction of R358 alpha 1-AT with thrombin may involve the VR1 subsite. We also obtained evidence that VR1 may be involved in the activation of protein C by thrombin in the absence of thrombomodulin. Moreover, IgG D attenuated the inhibitory effect of calcium ions during protein C activation by thrombin, probably by masking E39 within the VR1 site.