Interactions of Fibrinogen Gamma' Variant with Thrombin

描述（由申请人提供）：我的长期目标是确定纤维蛋白原和凝血酶的γ变体形式之间的相互作用。这项建议的具体目标是： I-绘制γ链上的Ca2+结合位点。待检验的假设是γ链在f中提供了额外的Ca2+结合位点。brinogen.II - 确定γ链对凝血酶对蛋白质底物的酶活性的影响。待检验的假设是γ链通过与外位点II结合来调节凝血酶对底物的裂解。 III-确定γ链对蛋白酶抑制剂抑制凝血酶的作用。待检验的假设是γ链的纤溶酶裂解产物催化肝素依赖性抑制剂对凝血酶的抑制，且γ链与肝素依赖性抑制剂结合。 IV-确定γ链对整个血浆中凝血酶的促凝血活性和血小板聚集活性的影响。待检验的假设是γ链的纤溶酶裂解产物在血浆中充当抗凝剂。

DESCRIPTION (provided by applicant): My long-term goals are to define the interactions between the gamma variant form of fibrinogen and thrombin. The specific aims of this proposal are to: I- Map the Ca2+ binding site(s) on the gamma chain. The hypothesis to be tested is that the gamma chain provides an additional Ca2+ binding site(s) in fbrinogen.II - Determine the effect of the gamma chain on thrombin's enzymatic activity towards protein substrates. The hypothesis to be tested is that the gamma chain modulates thrombin cleavage of substrates by binding to exosite II. III- Determine the effect of the gamma chain on thrombin inhibition by protease inhibitors. The hypothesis to be tested is that a plasmin cleavage product of the gamma chain catalyzes thrombin inhibition by heparin-dependent inhibitors, and that the gamma chain binds to heparin-dependent inhibitors. IV- Determine the effect of the gamma chain on thrombin's procoagulant activity and platelet aggregating activity in whole plasma. The hypothesis to be tested is that a plasmin cleavage product of the gamma chain acts as an anticoagulant in plasma.