Kim, SJ Woo, JR Seo, EJ Yu, MH Ryu, SE 2024-01-21T12:43:22Z 2024-01-21T12:43:22Z 2021-09-05 2001-02-09 0022-2836 https://pubs.kist.re.kr/handle/201004/140710 Serpin (serine protease inhibitor) proteins are involved in diverse physiological processes including inflammation, coagulation, matrix remodeling, and cell differentiation. Deficiency of normal serpin functions leads to various hereditary diseases. Besides their clinical importance, serpin proteins draw much attention due to the large conformational changes that occur upon interaction with proteases. We present here the crystal structure of an uncleaved alpha (1)-antitrypsin determined by the multiple isomorphous replacement method and refined to 2.1 Angstrom resolution. The structure, which is the first active serpin structure based on experimental phases, reveals novel conformations in the flexible loops, including the proximal hinge region of the reactive center loop and the surface cavity region in the central beta -sheet, sheet A. The determined loop conformation explains the results of recent mutagenesis studies and provides detailed insights into the protease inhibition mechanism. The high-resolution structure of active alpha (1)-antitrypsin also provides evidence for the existence of localized van-der-Waals strain in the central hydrophobic core. (C) 2001 Academic Press. English ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD CRYSTAL-STRUCTURE INHIBITORY MECHANISM NATIVE STRAIN CONFORMATION REVEALS SERPINS MODEL ALPHA-1-ANTITRYPSIN MUTATIONS MOLSCRIPT A 2.1 angstrom resolution structure of an uncleaved alpha(1)-antitrypsin shows variability of the reactive center and other loops Article 10.1006/jmbi.2000.4357 1 JOURNAL OF MOLECULAR BIOLOGY, v.306, no.1, pp.109 - 119 JOURNAL OF MOLECULAR BIOLOGY 306 1 109 119 scie scopus 000166919300010 2-s2.0-0035830479 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article CRYSTAL-STRUCTURE INHIBITORY MECHANISM NATIVE STRAIN CONFORMATION REVEALS SERPINS MODEL ALPHA-1-ANTITRYPSIN MUTATIONS MOLSCRIPT alpha(1)-antitrypsin serpins reactive center loop van-der-Waals strain surface cavity