2bey
From Proteopedia
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==Overview== | ==Overview== | ||
| - | 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, ... | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2BEY is a | + | 2BEY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Structure known Active Site: P1A. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BEY OCA]. |
==Reference== | ==Reference== | ||
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[[Category: symmetry]] | [[Category: symmetry]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:54:32 2007'' |
Revision as of 12:49, 5 November 2007
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SOLUTION STRUCTURE OF A NOVEL C2 SYMMETRICAL BIFUNCTIONAL BICYCLIC INHIBITOR BASED ON SFTI-1
Overview
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.
About this Structure
2BEY is a Single protein structure of sequence from [1]. Structure known Active Site: P1A. Full crystallographic information is available from OCA.
Reference
Solution structure of a novel C2-symmetrical bifunctional bicyclic inhibitor based on SFTI-1., Jaulent AM, Brauer AB, Matthews SJ, Leatherbarrow RJ, J Biomol NMR. 2005 Sep;33(1):57-62. PMID:16222558
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