DC Field | Value | Language |
---|---|---|
dc.contributor.author | Seong Eon Ryu | - |
dc.contributor.author | Hee Jeong Choi | - |
dc.contributor.author | Ki Sun Kwon | - |
dc.contributor.author | Kee Nyung Lee | - |
dc.contributor.author | Myeong Hee Yu | - |
dc.date.accessioned | 2017-04-19T08:45:42Z | - |
dc.date.available | 2017-04-19T08:45:42Z | - |
dc.date.issued | 1996 | - |
dc.identifier.issn | 0969-2126 | - |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/3864 | - |
dc.description.abstract | Background: 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.publisher | Elsevier-Cell Press | - |
dc.title | 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 | - |
dc.title.alternative | 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 | - |
dc.type | Article | - |
dc.citation.title | Structure | - |
dc.citation.number | 0 | - |
dc.citation.endPage | 1192 | - |
dc.citation.startPage | 1181 | - |
dc.citation.volume | 4 | - |
dc.contributor.affiliatedAuthor | Seong Eon Ryu | - |
dc.contributor.affiliatedAuthor | Hee Jeong Choi | - |
dc.contributor.affiliatedAuthor | Ki Sun Kwon | - |
dc.contributor.affiliatedAuthor | Kee Nyung Lee | - |
dc.contributor.affiliatedAuthor | Myeong Hee Yu | - |
dc.contributor.alternativeName | 류성언 | - |
dc.contributor.alternativeName | 최희정 | - |
dc.contributor.alternativeName | 권기선 | - |
dc.contributor.alternativeName | 이기녕 | - |
dc.contributor.alternativeName | 유명희 | - |
dc.identifier.bibliographicCitation | Structure, vol. 4, pp. 1181-1192 | - |
dc.identifier.doi | 10.1016/S0969-2126(96)00126-8 | - |
dc.subject.keyword | conformational transition | - |
dc.subject.keyword | loop flexibility | - |
dc.subject.keyword | metastability | - |
dc.subject.keyword | stabilizing mutations | - |
dc.subject.keyword | α1-antitrypsin | - |
dc.subject.local | conformational transition | - |
dc.subject.local | loop flexibility | - |
dc.subject.local | metastability | - |
dc.subject.local | stabilizing mutations | - |
dc.subject.local | alpha 1 antitrypsin | - |
dc.subject.local | α 1-antitrypsin | - |
dc.subject.local | α1-antitrypsin | - |
dc.subject.local | Alpha1-antitrypsin | - |
dc.subject.local | alpha 1-Antitrypsin | - |
dc.subject.local | α1-Antitrypsin | - |
dc.description.journalClass | Y | - |
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