1JBL

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

1JBL の概要

• エントリーDOI: 10.2210/pdb1jbl/pdb
• 関連するPDBエントリー: 1JBN
• 関連するBIRD辞書のPRD_ID: PRD_001097
• 分子名称: CYCLIC TRYPSIN INHIBITOR (1 entity in total)
• 機能のキーワード: cyclic backbone, 2 beta strands, 1 disulfide bond, sfti-1, protein binding
• 由来する生物種: Helianthus annuus (common sunflower)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1535.83

構造登録者

Korsinczky, M.L.J.,Schirra, H.J.,Rosengren, K.J.,West, J.,Condie, B.A.,Otvos, L.,Anderson, M.A.,Craik, D.J. (登録日: 2001-06-05, 公開日: 2001-08-22, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

SOLUTION NMR