The structure of a two-disulfide intermediate assists in elucidating the oxidative folding pathway of a cyclic cystine knot protein

Cemazar, M., Joshi, A., Daly, N. L., Mark, A. E. and Craik, D. J. (2008) The structure of a two-disulfide intermediate assists in elucidating the oxidative folding pathway of a cyclic cystine knot protein. Structure, 16 6: 842-851. doi:10.1016/j.str.2008.02.023


Author Cemazar, M.
Joshi, A.
Daly, N. L.
Mark, A. E.
Craik, D. J.
Title The structure of a two-disulfide intermediate assists in elucidating the oxidative folding pathway of a cyclic cystine knot protein
Journal name Structure   Check publisher's open access policy
ISSN 0969-2126
Publication date 2008-06-01
Sub-type Article (original research)
DOI 10.1016/j.str.2008.02.023
Volume 16
Issue 6
Start page 842
End page 851
Total pages 10
Place of publication United States
Publisher Cell Press
Collection year 2009
Language eng
Subject C1
030403 Characterisation of Biological Macromolecules
030402 Biomolecular Modelling and Design
970106 Expanding Knowledge in the Biological Sciences
Abstract We have determined the three-dimensional structure of a two-disulfide intermediate (Cys8-Cys20, Cys14-Cys26) on the oxidative folding pathway of the cyclotide MCoTI-II. Cyclotides have a range of bioactivities and, because of their exceptional stability, have been proposed as potential molecular scaffolds for drug design applications. The three-dimensional structure of the stable two-disulfide intermediate shows for the most part identical secondary and tertiary structure to the native state. The only exception is a flexible loop, which is collapsed onto the protein core in the native state, whereas in the intermediate it is more loosely associated with the remainder of the protein. The results suggest that the native fold of the peptide does not represent the free energy minimum in the absence of the Cys1-Cys18 disulfide bridge and that although there is not a large energy barrier, the peptide must transiently adopt an energetically unfavorable state before the final disulfide can form.
Keyword Proteins
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
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Created: Wed, 01 Apr 2009, 21:36:27 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences