Haemostasis Biochemistry, Novo Nordisk A/S, Måløv, Denmark.
Thromb Res. 2010 Apr;125 Suppl 1:S11-2. doi: 10.1016/j.thromres.2010.01.023. Epub 2010 Feb 13.
Free factor VIIa displays a zymogen-like behavior with low intrinsic activity. Formation of a complex between factor VIIa and tissue factor is necessary to enhance the procoagulant activity of factor VIIa, not only by providing membrane localization, substrate exosites and positioning the active site at an appropriate distance above the surface but also by allosteric enhancement of the enzymatic activity, and this event signals initiation of blood coagulation. The interaction is of high affinity and all the domains are engaged at the interface. The crosstalk between the protease domain of factor VIIa, in particular residue Met-306, and the N-terminal domain of tissue factor provides the starting point for the allosteric activation of factor VIIa. The pathway(s) of conformational transitions in factor VIIa ensuing tissue factor binding has not been entirely mapped. The present paper is a brief compilation of our current knowledge of the allosteric mechanism by which tissue factor induces and stabilizes the active conformation of factor VIIa.
游离型 VIIa 因子表现出类酶原的低固有活性行为。VIIa 因子与组织因子形成复合物，不仅通过提供膜定位、底物外显子和将活性位点定位在距表面适当的距离，而且通过变构增强酶活性，从而增强 VIIa 因子的促凝活性，这一事件标志着血液凝固的开始。这种相互作用具有高亲和力，所有结构域都在界面上结合。VIIa 因子的蛋白酶结构域（特别是残基 Met-306）与组织因子的 N 端结构域之间的串扰为 VIIa 因子的变构激活提供了起点。组织因子结合后 VIIa 因子构象转变的途径尚未完全确定。本文简要总结了我们目前对组织因子诱导和稳定 VIIa 因子活性构象的变构机制的认识。
