Abstract：
:The clinical effects of serpin polymerisation include thromboembolism, emphysema, and liver disease. A through understanding of serpin polymerisation mechanisms and the structures involved will permit the rational design of therapeutic polymerisation inhibitors. Here we show that serpin polymerisation can be delayed by extending the length of the serpin reactive centre loop. The heat stability of three chimeric serpins was examined. One of them, an active alpha 1-antitrypsin variant with a reactive centre loop C-terminal extension of four amino acid residues, was shown to have increased resistance to inactivation by polymerisation. This variant could also form serpin/peptide binary complexes with a reactive centre loop peptide, which indicates that the increase in thermostability was not due to the A-beta-sheet being unable to accept reactive centre loop residues, an essential requirement for polymerisation. Rather, we conclude that the additional residues within the reactive centre loop delay the release of strand 1C from the C-sheet, a process essential for polymer formation.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Bottomley SP,Chang WSdoi
10.1006/bbrc.1997.7805subject
Has Abstractpub_date
1997-12-18 00:00:00pages
264-9issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(97)97805-0journal_volume
241pub_type
杂志文章abstract：:PQBP-1 was identified as a binding protein to the polyglutamine tract present in various transcription-related factors and causative genes for neurodegenerative disorders. This novel gene contains at least two functional domains, WW domain and carboxyl-terminal domain (CTD), strictly conserved beyond species. Although...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1006/bbrc.2000.2992
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journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1006/bbrc.1999.1932
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journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
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journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1006/bbrc.1997.7004
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journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
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journal_title：Biochemical and biophysical research communications
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doi：10.1006/bbrc.1996.1595
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1006/bbrc.1995.2461
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
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更新日期：2006-07-28 00:00:00
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journal_title：Biochemical and biophysical research communications
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journal_title：Biochemical and biophysical research communications
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更新日期：2005-01-28 00:00:00
