The native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor : crystal structure of an uncleaved α₁-antitrypsin at 2.7 A

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dc.contributor.authorSeong Eon Ryu-
dc.contributor.authorHee Jeong Choi-
dc.contributor.authorKi Sun Kwon-
dc.contributor.authorKee Nyung Lee-
dc.contributor.authorMyeong Hee Yu-
dc.date.accessioned2017-04-19T08:45:42Z-
dc.date.available2017-04-19T08:45:42Z-
dc.date.issued1996-
dc.identifier.issn0969-2126-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/3864-
dc.description.abstractBackground: The protein α1-antitrypsin is a prototype member of the serpin (serine protease inhibitor) family and is known to inhibit the activity of neutrophil elastase in the lower respiratory tract. Members of this family undergo a large structural rearrangement upon binding to a target protease, involving cleavage of the reactive-site loop. This loop is then inserted into the main body of the enzyme following the opening of a central β sheet, leading to stabilization of the structure. Random mutageneses of α1-antitrypsin identified various mutations that stabilize the native structure and retard the insertion of the reactive-site loop. Structural studies of these mutations may reveal the mechanism of the conformational change. Results: We have determined the three-dimensional structure of an uncleaved α1-antitrypsin with seven such stabilizing mutations (hepta α1- antitrypsin) at 2.7 A resolution. From the comparison of the structure with other serpin structures, we found that hepta α1-antitrypsin is stabilized due to the release of various strains that exist in native wild type α1- antitrypsin, including unfavorable hydrophobic interactions in the central hydrophobic core. The reactive-site loop of hepta α1-antitrypsin is an extended strand, different from that of the previously determined structure of another uncleaved α1-antitrypsin, and indicates the inherent flexibility of the loop. Conclusions: The present structural study suggests that the uncleaved α1-antitrypsin has many folding defects which can be improved by mutations. These folding defects seem to be utilized in a coordinated fashion in the regulation of the conformational switch of α1-antitrypsin. Some of the defects, represented by the Phe51 region and possibly the Met374 and the Thr59 regions, are part of the sheet-opening mechanism.-
dc.publisherElsevier-Cell Press-
dc.titleThe native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor : crystal structure of an uncleaved α₁-antitrypsin at 2.7 A-
dc.title.alternativeThe native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor : crystal structure of an uncleaved α₁-antitrypsin at 2.7 A-
dc.typeArticle-
dc.citation.titleStructure-
dc.citation.number0-
dc.citation.endPage1192-
dc.citation.startPage1181-
dc.citation.volume4-
dc.contributor.affiliatedAuthorSeong Eon Ryu-
dc.contributor.affiliatedAuthorHee Jeong Choi-
dc.contributor.affiliatedAuthorKi Sun Kwon-
dc.contributor.affiliatedAuthorKee Nyung Lee-
dc.contributor.affiliatedAuthorMyeong Hee Yu-
dc.contributor.alternativeName류성언-
dc.contributor.alternativeName최희정-
dc.contributor.alternativeName권기선-
dc.contributor.alternativeName이기녕-
dc.contributor.alternativeName유명희-
dc.identifier.bibliographicCitationStructure, vol. 4, pp. 1181-1192-
dc.identifier.doi10.1016/S0969-2126(96)00126-8-
dc.subject.keywordconformational transition-
dc.subject.keywordloop flexibility-
dc.subject.keywordmetastability-
dc.subject.keywordstabilizing mutations-
dc.subject.keywordα1-antitrypsin-
dc.subject.localconformational transition-
dc.subject.localloop flexibility-
dc.subject.localmetastability-
dc.subject.localstabilizing mutations-
dc.subject.localalpha 1 antitrypsin-
dc.subject.localα 1-antitrypsin-
dc.subject.localα1-antitrypsin-
dc.subject.localAlpha1-antitrypsin-
dc.subject.localalpha 1-Antitrypsin-
dc.subject.localα1-Antitrypsin-
dc.description.journalClassY-
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Aging Convergence Research Center > 1. Journal Articles
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