Lee, C Seo, EJ Yu, MH 2024-01-21T11:43:44Z 2024-01-21T11:43:44Z 2021-09-05 2001-09-28 0006-291X https://pubs.kist.re.kr/handle/201004/140172 The native form of serpins (serine protease inhibitors) is metastable, which is critical to their biological functions. Spontaneous conversion from the native form of serpins into a more stable conformation, called the "latent" form, is restricted. To examine whether the connectivity of strand 1 of beta -sheet C to the hydrophobic core is critical to the serpin's preferential folding to the metastable native conformation, we designed a circularly-permuted mutant of alpha (1)-antitrypsin, the prototype serpin, in which strand 1C is disconnected from the hydrophobic core. Conformation of the circular permutant was similar to that of the latent form, as revealed by equilibrium unfolding, limited proteolysis, and spectroscopic properties. Our results support the notion that rapid folding of the hydrophobic core with concomitant incorporation of strand 1C into beta -sheet C traps the serpin molecule into its native metastable conformation. (C) 2001 Academic Press. English ACADEMIC PRESS INC PLASMINOGEN-ACTIVATOR INHIBITOR-1 INFLUENZA HEMAGGLUTININ ALPHA-1-PROTEINASE INHIBITOR ESCHERICHIA-COLI PROTEIN FUNCTION REACTIVE CENTER SERPINS CONFORMATION STABILITY LOOP Role of the connectivity of secondary structure segments in the folding of alpha(1)-antitrypsin Article 10.1006/bbrc.2001.5638 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.287, no.3, pp.636 - 641 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 287 3 636 641 scie scopus 000171400200008 2-s2.0-0035964912 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article PLASMINOGEN-ACTIVATOR INHIBITOR-1 INFLUENZA HEMAGGLUTININ ALPHA-1-PROTEINASE INHIBITOR ESCHERICHIA-COLI PROTEIN FUNCTION REACTIVE CENTER SERPINS CONFORMATION STABILITY LOOP serpin protein folding metastable state kinetic trap circular permutant alpha(1)-antitrypsin