A 2.1 angstrom resolution structure of an uncleaved alpha(1)-antitrypsin shows variability of the reactive center and other loops

Authors
Kim, SJWoo, JRSeo, EJYu, MHRyu, SE
Issue Date
2001-02-09
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Citation
JOURNAL OF MOLECULAR BIOLOGY, v.306, no.1, pp.109 - 119
Abstract
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.
Keywords
CRYSTAL-STRUCTURE; INHIBITORY MECHANISM; NATIVE STRAIN; CONFORMATION; REVEALS; SERPINS; MODEL; ALPHA-1-ANTITRYPSIN; MUTATIONS; MOLSCRIPT; 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
ISSN
0022-2836
URI
https://pubs.kist.re.kr/handle/201004/140710
DOI
10.1006/jmbi.2000.4357
Appears in Collections:
KIST Article > 2001
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