Fitzpatrick P A, Wong D T, Barr P J, Pemberton P A
LXR Biotechnology, Richmond, CA 94804, USA.
Protein Eng. 1996 Jul;9(7):585-9. doi: 10.1093/protein/9.7.585.
The tumor suppressor maspin (mammary-specific serpin) is an unstable serpin that does not undergo the stressed to relaxed transition typical of proteinase inhibitory serpins and, consequently, is not likely to function as a serine proteinase inhibitor. This suggests that the positioning and configuration of the reactive site loop (RSL) of maspin are likely to resemble those of ovalbumin, the best studied non-inhibitory serpin. Accordingly, the tertiary structure of maspin has been modeled on the crystal structure of native ovalbumin. Biochemical data and the modeled theoretical structure of maspin reveal the absence of disulfide bonds in the molecule and the presence of an unstable RSL that adopts a distorted helical structure. We confirm that the RSL is extremely sensitive to limited proteolysis and suggest that this may provide a structural basis for the proteolytic inactivation of maspin, a process that is likely to modulate the activity of maspin in biological systems.
肿瘤抑制因子maspin（乳腺特异性丝氨酸蛋白酶抑制剂）是一种不稳定的丝氨酸蛋白酶抑制剂，它不会经历典型的蛋白酶抑制性丝氨酸蛋白酶抑制剂从应激状态到松弛状态的转变，因此，它不太可能作为丝氨酸蛋白酶抑制剂发挥作用。这表明maspin反应位点环（RSL）的定位和构型可能与卵清蛋白相似，卵清蛋白是研究最深入的非抑制性丝氨酸蛋白酶抑制剂。因此，maspin的三级结构是根据天然卵清蛋白的晶体结构构建的。maspin的生化数据和模拟理论结构显示，该分子中不存在二硫键，且存在一个采用扭曲螺旋结构的不稳定RSL。我们证实RSL对有限的蛋白水解作用极为敏感，并表明这可能为maspin的蛋白水解失活提供结构基础，这一过程可能在生物系统中调节maspin的活性。
