Cho Ye-Lim, Chae Young Kee, Jung Chan-Hun, Kim Min-Jung, Na Yu-Ran, Kim Yang-Hee, Kang Shin-Jung, Im Hana
Department of Molecular Biology and Applied Chemistry, Research Center for Conformational Degenerative Diseases, Sejong University, 98 Gunja-dong, Kwangjin-gu, Seoul 143-747, Korea.
Protein Pept Lett. 2005 Jul;12(5):477-81. doi: 10.2174/0929866054395365.
The native metastability of serine protease inhibitors (serpins) is believed to facilitate the conformational change required for biological function. However, energetically unfavorable structural features that contribute to metastability of the native serpin conformation, such as buried polar groups, cavities, and over-packing of side-chains, also appear to hinder proper folding. Hence, folding of serpin polypeptides appears prone to error; in particular, the folding polypeptides are readily diverted toward a non-productive folding pathway culminating in a more stable but inactive conformation. In a survey of deficient serpin mutants, various folding defects, such as retarded protein folding, destabilized native conformation, and spontaneous conversion into more stable, inactive conformations such as the latent form and loop-sheet polymers, have been discovered.
丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）的天然亚稳定性被认为有助于生物功能所需的构象变化。然而，导致天然丝氨酸蛋白酶抑制剂构象亚稳定性的能量上不利的结构特征，如埋藏的极性基团、空洞和侧链过度堆积，似乎也阻碍了正确折叠。因此，丝氨酸蛋白酶抑制剂多肽的折叠似乎容易出错；特别是，折叠中的多肽很容易转向非生产性折叠途径，最终形成更稳定但无活性的构象。在对缺陷型丝氨酸蛋白酶抑制剂突变体的调查中，发现了各种折叠缺陷，如蛋白质折叠延迟、天然构象不稳定以及自发转化为更稳定的无活性构象，如潜伏形式和环片聚合物。
