Johnson K, Zaror I, Bauer D, Choi Y, Creasey A, Innis M
Chiron Technologies, Chiron Corporation, Emeryville, CA 94608, USA.
Thromb Haemost. 1998 Oct;80(4):585-7.
Tissue factor pathway inhibitors (TFPI and TFPI-2) are Kunitz domain-type serine protease inhibitors which inhibit factor VIIa/tissue factor (VIIa/TF) complexes in a factor Xa-dependent manner. The VIIa/TF and Xa inhibitory activity has been localized to the first two Kunitz domains, respectively. Unlike TFPI, TFPI-2 has been reported to exhibit significant Xa-independent VIIa/TF inhibitory activity, perhaps due to an arginine at the P1 residue in the first Kunitz domain of TFPI-2 as opposed to a lysine at the comparable residue in TFPI. Two domain TFPI variants, differing in the first Kunitz domain but containing the second Kunitz domain of TFPI, were constructed and secreted by Saccharomyces cerevisiae in order to test the possibility that a TFPI first Kunitz domain with a P1 lysine to arginine change or a hybrid containing the TFPI-2 first Kunitz domain may represent more potent VIIa/TF inhibitors. When yeast supernatants were analyzed for specific activity in the Xa-dependent inhibition of VIIa/TF, neither variant was as active as the truncated TFPI.
组织因子途径抑制剂（TFPI和TFPI-2）是库尼兹结构域型丝氨酸蛋白酶抑制剂，它们以因子Xa依赖的方式抑制因子VIIa/组织因子（VIIa/TF）复合物。VIIa/TF和Xa抑制活性分别定位于前两个库尼兹结构域。与TFPI不同，据报道TFPI-2表现出显著的不依赖Xa的VIIa/TF抑制活性，这可能是由于TFPI-2第一个库尼兹结构域中P1残基处为精氨酸，而TFPI中相应残基处为赖氨酸。构建了在第一个库尼兹结构域不同但包含TFPI第二个库尼兹结构域的两个结构域TFPI变体，并由酿酒酵母分泌，以测试第一个库尼兹结构域中P1赖氨酸变为精氨酸的TFPI或包含TFPI-2第一个库尼兹结构域的杂交体可能代表更有效的VIIa/TF抑制剂的可能性。当分析酵母上清液在Xa依赖的VIIa/TF抑制中的比活性时，两种变体的活性均不如截短的TFPI。
