Isolation of a protein Z-dependent plasma protease inhibitor
Isolation of a protein Z-dependent plasma protease inhibitor
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DOI：
10.1073/pnas.95.16.9250
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Broze, GJ
中科院分区：
文献类型：
--
作者：
Han, X;Fiehler, R;Broze, GJ
人蛋白Z（PZ）是一种62，000-M-r的维生素It依赖性血浆蛋白，其结构类似于凝血因子VII、IX、X、蛋白C和蛋白S，但其功能尚不清楚。当因子Xa首次与PZ孵育时，因子Xa在一期血浆凝固试验中的促凝活性降低。这种明显的抑制作用具有时间依赖性，需要钙离子和促凝血磷脂（兔脑磷脂）的存在，并且似乎主要与PZ与脑磷脂的孵育期相关。在血清中，存在PZ时，钙离子和脑磷脂对因子XA的初始抑制率也得到增强。从血浆中分离出一种PZ依赖性蛋白酶抑制剂（ZPI）。ZPI是一种72，000-M-r单链蛋白，其N-末端氨基酸序列为LAPSPQSPEXXA（X =不确定），在柠檬酸盐处理的血浆中的估计浓度为1.0-1.6 μ g/ml。在使用纯化组分的系统中，由ZPI产生的因子Xa抑制是快速的（通过凝血测定在1分钟内>95%）并且需要PZ、钙离子和脑磷脂的存在。抑制过程似乎涉及在磷脂表面形成因子Xa-PZ-ZPI复合物。
Human protein Z (PZ) is a 62,000-M-r, vitamin It-dependent plasma protein whose structure is similar to coagulation factors VII, IX, X, protein C, and protein S, but whose function is not known. The procoagulant activity of factor Xa in a one-stage plasma coagulation assay is reduced when factor Xa is first incubated with PZ. This apparent inhibitory effect is time dependent, requires the presence of calcium ions and procoagulant phospholipids (rabbit brain cephalin), and appears predominantly related to the incubation period of PZ with cephalin. In serum the initial rate of inhibition of factor Xa with calcium ions and cephalin also is enhanced in the presence PZ. A PZ-dependent protease inhibitor (ZPI) has been isolated from plasma. ZPI is a 72,000-M-r single-chain protein with an N-terminal amino acid sequence of LAPSPQSPEXXA (X = indeterminate) and an estimated concentration in citrate-treated plasma of 1.0-1.6 mu g/ml. In systems using purified components, the factor Xa inhibition produced by ZPI is rapid (>95% within I min by coagulation assay) and requires the presence of PZ, calcium ions, and cephalin. The inhibitory process appears to involve the formation of a factor Xa-PZ-ZPI complex at the plospholipid surface.