Manipulation of the membrane binding site of vitamin K-dependent proteins: enhanced biological function of human factor VII.
Manipulation of the membrane binding site of vitamin K-dependent proteins: enhanced biological function of human factor VII.
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维生素 K 依赖性蛋白膜结合位点的操作：增强人类因子 VII 的生物学功能。
DOI：
10.1073/pnas.95.8.4229
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发表时间：
1998
影响因子：
11.1
通讯作者：
Nelsestuen,GL
中科院分区：
文献类型：
--
作者：
Shah,AM;Kisiel,W;Foster,DC;Nelsestuen,GL
最近的研究表明，修饰维生素K依赖蛋白的膜接触部位可能会增强该蛋白家族成员的膜亲和力和功能。比较了凝血因子VII突变体，凝血因子VII-Q10E32与野生型凝血因子VII(含P10K32)的性质。VII-Q10E32的膜亲和力比野生型VII高约20倍，用可溶性组织因子激活VII-Q10E32的速率比野生型VII快100倍，被Xa因子激活的速率是野生型VII的30倍。当与可溶性组织因子和磷脂结合时，激活的VII-Q10E32显示出对凝血因子X的激活。在所有类型的血浆和所有受试组织因子来源中，其凝血活性都增强。当凝血条件最小时，这种活性差异(最大为50倍)最大，例如限制组织因子和/或磷脂的水平。由于其增强的活性，因子VII-Q10E32及其衍生物可能为研究提供重要的试剂，并可能在治疗出血和/或凝血障碍方面更有效。
Recent studies suggested that modification of the membrane contact site of vitamin K-dependent proteins may enhance the membrane affinity and function of members of this protein family. The properties of a factor VII mutant, factor VII-Q10E32, relative to wild-type factor VII (VII, containing P10K32), have been compared. Membrane affinity of VII-Q10E32 was about 20-fold higher than that of wild-type factor VII. The rate of autoactivation VII-Q10E32 with soluble tissue factor was 100-fold faster than wild-type VII and its rate of activation by factor Xa was 30 times greater than that of wild-type factor VII. When combined with soluble tissue factor and phospholipid, activated factor VII-Q10E32 displayed increased activation of factor X. Its coagulant activity was enhanced in all types of plasma and with all sources of tissue factor tested. This difference in activity (maximum 50-fold) was greatest when coagulation conditions were minimal, such as limiting levels of tissue factor and/or phospholipid. Because of its enhanced activity, factor VII-Q10E32 and its derivatives may provide important reagents for research and may be more effective in treatment of bleeding and/or clotting disorders.