Solution structures by H-1 NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant

Korsinczky, M. L. J., Schirra, H. J., Rosengren, K. J., West, J., Condie, B. A., Otvos, L., Anderson, M. A. and Craik, D. J. (2001) Solution structures by H-1 NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant. Journal of Molecular Biology, 311 3: 579-591. doi:10.1006/jmbi.2001.4887

Author Korsinczky, M. L. J.
Schirra, H. J.
Rosengren, K. J.
West, J.
Condie, B. A.
Otvos, L.
Anderson, M. A.
Craik, D. J.
Title Solution structures by H-1 NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant
Journal name Journal of Molecular Biology   Check publisher's open access policy
ISSN 0022-2836
Publication date 2001-01-01
Year available 2001
Sub-type Article (original research)
DOI 10.1006/jmbi.2001.4887
Open Access Status Not yet assessed
Volume 311
Issue 3
Start page 579
End page 591
Total pages 13
Place of publication USA
Publisher Academic Press
Language eng
Subject C1
250302 Biological and Medical Chemistry
670403 Treatments (e.g. chemicals, antibiotics)
Abstract SFTI-1 is a recently discovered cyclic peptide trypsin inhibitor from sunflower seeds comprising 14 amino acid residues. It is the most potent known Bowman-Birk inhibitor and the only naturally occurring cyclic one. The solution structure of SFTI-1 has been determined by H-1-NMR spectroscopy and compared with a synthetic acyclic permutant. The solution structures of both are remarkably similar. The lowest energy structures from each family of 20 structures of cyclic and acyclic SFTI-1 have an rmsd over the backbone and heavy atoms of 0.29 Angstrom and 0.66 Angstrom, respectively. The structures consist of two short antiparallel beta -strands joined by an extended loop containing the active site at one end. Cyclic SFTI-1 also has a hairpin turn completing the cycle. Both molecules contain particularly stable arrangements of cross-linking hydrogen bonds between the beta -strands and a single disulfide bridge, making them rigid and well defined in solution. These stable arrangements allow both the cyclic and acyclic variants of SFTI-1 to inhibit trypsin with very high potencies (0.5 nM and 12.1 nM, respectively). The cyclic nature of SFTI-1 appears to have evolved to provide higher trypsin inhibition as well as higher stability. The solution structures are similar to the crystal structure of the cyclic inhibitor in complex with trypsin. The lack of a major conformational change upon binding suggests that the structure of SFTI-1 is rigid and already pre-organized for maximal binding due to minimization of entropic losses compared to a more flexible ligand. These properties make SFTI-1 an ideal platform for the design of small peptidic pharmaceuticals or pesticides. (C) 2001 Academic Press.
Keyword Biochemistry & Molecular Biology
Circular Proteins
Cyclic Peptide
Bowman-birk Inhibitor
Trypsin Inhibitor
Cystine Knot
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Created: Wed, 15 Aug 2007, 01:46:56 EST