HUMAN THROMBIN VARIABLE REGION-1, INCLUDING E39, IS INVOLVED IN INTERACTIONS WITH ALPHA-1-ANTITRYPSIN M358R AND PROTEIN-C

We used an antithrombin autoantibody (IgG D), the epitope of which enc ompasses ABE1 and amino acids located within variable region 1, to stu dy thrombin interactions with R358 alpha 1-AT and protein C. IgG D inh ibited the thrombin interaction with R358 alpha 1-AT, while hirugen ha d no effect, indicating that the interaction of R358 alpha 1-AT with t hrombin may involve the VR1 subsite, We also obtained evidence that VR 1 may be involved in the activation of protein C by thrombin in the ab sence of thrombomodulin. Moreover, IgG D attenuated the inhibitory eff ect of calcium ions during protein C activation by thrombin, probably by masking E 39 within the VR1 site.