title: The native metastability and misfolding of serine protease inhibitors.
abstract: 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.
authors: Department of Molecular Biology and Applied Chemistry, Research Center for Conformational Degenerative Diseases, Sejong University, 98 Gunja-dong, Kwangjin-gu, Seoul 143-747, Korea.
authors: Ye-Lim
authors: YL
authors: Cho
authors: Young Kee
authors: YK
authors: Chae
authors: Chan-Hun
authors: CH
authors: Jung
authors: Min-Jung
authors: MJ
authors: Kim
authors: Yu-Ran
authors: YR
authors: Na
authors: Yang-Hee
authors: YH
authors: Kim
authors: Shin-Jung
authors: SJ
authors: Kang
authors: Hana
authors: H
authors: Im
mesh_terms: D000682:Amyloid / Q000096:biosynthesis; D007700:Kinetics; D009154:Mutation; D011108:Polymers / Q000737:chemistry; D017510:Protein Folding; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000502:physiology*; D015843:Serpins / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D000682:Amyloid; D011108:Polymers; D015842:Serine Proteinase Inhibitors; D015843:Serpins