1JBL

Solution structure of SFTI-1, A cyclic trypsin inhibitor from sunflower seeds

Summary for 1JBL

• Entry DOI: 10.2210/pdb1jbl/pdb
• Related: 1JBN
• Related PRD ID: PRD_001097
• Descriptor: CYCLIC TRYPSIN INHIBITOR (1 entity in total)
• Functional Keywords: cyclic backbone, 2 beta strands, 1 disulfide bond, sfti-1, protein binding
• Biological source: Helianthus annuus (common sunflower)
• Total number of polymer chains: 1
• Total formula weight: 1535.83

Authors

Korsinczky, M.L.J.,Schirra, H.J.,Rosengren, K.J.,West, J.,Condie, B.A.,Otvos, L.,Anderson, M.A.,Craik, D.J. (deposition date: 2001-06-05, release date: 2001-08-22, Last modification date: 2024-11-13)

Primary citation

Korsinczky, M.L.,Schirra, H.J.,Rosengren, K.J.,West, J.,Condie, B.A.,Otvos, L.,Anderson, M.A.,Craik, D.J.
Solution structures by 1H NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant.
J.Mol.Biol., 311:579-591, 2001

PubMed 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 1H-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 A and 0.66 A, 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.

PubMed: 11493011
DOI: 10.1006/jmbi.2001.4887

Experimental method

SOLUTION NMR