2bey: Difference between revisions

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==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.

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==

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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16222558 16222558]

[[Category: Single protein]]

[[Category: Brauer, A.B.E.]]

[[Category: Brauer, A B.E.]]

[[Category: Jaulent, A.M.]]

[[Category: Jaulent, A M.]]

[[Category: Leatherbarrow, R.J.]]

[[Category: Leatherbarrow, R J.]]

[[Category: Matthews, S.J.]]

[[Category: Matthews, S J.]]

[[Category: bikk]]

[[Category: c2 symmetrical bifunctional bicyclic trypsin inhibitor]]

Line 22:

[[Category: symmetry]]

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@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 12: / Line 12: @@
 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16222558 16222558]
 [[Category: Single protein]]
-[[Category: Brauer, A.B.E.]]
+[[Category: Brauer, A B.E.]]
-[[Category: Jaulent, A.M.]]
+[[Category: Jaulent, A M.]]
-[[Category: Leatherbarrow, R.J.]]
+[[Category: Leatherbarrow, R J.]]
-[[Category: Matthews, S.J.]]
+[[Category: Matthews, S J.]]
 [[Category: bikk]]
 [[Category: c2 symmetrical bifunctional bicyclic trypsin inhibitor]]
@@ Line 22: / Line 22: @@
 [[Category: symmetry]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:23:16 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:37:14 2008''