2BEY

Solution Structure of a Novel C2 Symmetrical Bifunctional Bicyclic Inhibitor Based on SFTI-1

Summary for 2BEY

• Entry DOI: 10.2210/pdb2bey/pdb
• Descriptor: BIKK (1 entity in total)
• Functional Keywords: inhibitor, bikk, c2 symmetrical bifunctional bicyclic trypsin inhibitor, symmetry, sfti1
• Biological source: SYNTHETIC CONSTRUCT
• Total number of polymer chains: 1
• Total formula weight: 1700.11

Authors

Jaulent, A.M.,Brauer, A.B.E.,Matthews, S.J.,Leatherbarrow, R.J. (deposition date: 2004-12-01, release date: 2005-10-17, Last modification date: 2024-11-20)

Primary citation

Jaulent, A.M.,Brauer, A.B.E.,Matthews, S.J.,Leatherbarrow, R.J.
Solution Structure of a Novel C2-Symmetrical Bifunctional Bicyclic Inhibitor Based on Sfti-1
J.Biomol.NMR, 33:57-, 2005

PubMed Abstract: A novel bifunctional bicyclic inhibitor has been created that combines features both from the Bowman-Birk inhibitor (BBI) proteins, which have two distinct inhibitory sites, and from sunflower trypsin inhibitor-1 (SFTI-1), which has a compact bicyclic structure. The inhibitor was designed by fusing together a pair of reactive loops based on a sequence derived from SFTI-1 to create a backbone-cyclized disulfide-bridged 16-mer peptide. This peptide has two symmetrically spaced trypsin binding sites. Its synthesis and biological activity have been reported in a previous communication [Jaulent and Leatherbarrow, 2004, PEDS 17, 681]. In the present study we have examined the three-dimensional structure of the molecule. We find that the new inhibitor, which has a symmetrical 8-mer half-cystine CTKSIPP'I' motif repeated through a C2 symmetry axis also shows a complete symmetry in its three-dimensional structure. Each of the two loops adopts the expected canonical conformation common to all BBIs as well as SFTI-1. We also find that the inhibitor displays a strong and unique structural identity, with a notable lack of minor conformational isomers that characterise most reactive site loop mimics examined to date as well as SFTI-1. This suggests that the presence of the additional cyclic loop acts to restrict conformational mobility and that the deliberate introduction of cyclic symmetry may offer a general route to locking the conformation of beta-hairpin structures.

PubMed: 16222558
DOI: 10.1007/S10858-005-1210-9

Experimental method

SOLUTION NMR