PMID: 8612799Mar 25, 1996Paper

Significance of secondary structure predictions on the reactive center loop region of serpins: a model for the folding of serpins into a metastable state

FEBS Letters
P A Patston, P G Gettins

Abstract

To address how serpins might fold so as to adopt the mechanistically required metastable conformation we have compared the predicted secondary structures of the reactive center loops (RCLs) of a large number of serpins with those of the equivalent regions of other non-serpin protein proteinase inhibitors. Whereas the RCLs of non-serpin inhibitors are predicted to be loop or beta-strand, those of inhibitory serpins are strongly predicted to be alpha-helical. However, non-inhibitory serpins, which also adopt the metastable conformation, show no consistent preference for alpha-helix. We propose that the RCL primary structure plays little role in promoting the metastable serpin conformation. Instead we hypothesize that preference for the metastable state results from the incorporation of part of the RCL into beta-sheet C, which as a consequence precludes incorporation of the RCL into beta-sheet A to give the most stable conformation. Consequently the RCL must be exposed and by default will adopt the most stable conformation in this particular context, which is likely to be an alpha-helix irrespective of the primary structure. Thus the observed correlation between inhibitory properties in serpins and prediction of alpha-helix in the...Continue Reading

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Citations

May 25, 2002·The Journal of Biological Chemistry·Sabina JanciauskieneSten Eriksson
Sep 7, 2000·Protein Science : a Publication of the Protein Society·H ImM H Yu
Mar 21, 1998·The Journal of Biological Chemistry·C E Chaillan-Huntington, P A Patston
Aug 8, 1998·The Journal of Biological Chemistry·P NashG McFadden
Feb 16, 2002·Hypertension·Jérôme CélérierPierre Corvol
Aug 23, 2002·Protein Science : a Publication of the Protein Society·Thomas SulikowskiPhilip A Patston
Jan 9, 2001·Archives of Biochemistry and Biophysics·S A SudaP A Patston
May 9, 1997·Journal of Molecular Biology·C FrancartG Lippens
Jun 1, 1997·Analytical Biochemistry·M Gauthier, P A Patston
Sep 27, 2000·Biochimica Et Biophysica Acta·I Simonovic, P A Patston

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