1hd9
From Proteopedia
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==Overview== | ==Overview== | ||
| - | We have determined the NMR structure in aqueous solution of a | + | We have determined the NMR structure in aqueous solution of a disulphide-cyclised 11-residue peptide that forms a stable beta-hairpin, incorporating a type VIb beta-turn. The structure is found to be extremely well ordered for a short peptide, with the 30 lowest energy simulated annealing structures having an average pairwise r.m.s. deviation of only 0.36 A over the backbone. All but three side-chains adopt distinct conformations, allowing a detailed analysis of their involvement in cross-strand interactions. The peptide sequence analysed originates from a previously reported study, which identified potent inhibitors of human leukocyte elastase from screening a combinatorial peptide library based on the short protein beta-sheet segment that forms the reactive site loop of Bowman-Birk inhibitors. A detailed comparison of the peptide's solution structure with the corresponding region in the whole protein structure reveals a very good correspondence not only for the backbone (r.m.s. deviation approximately 0.7 A) but also for the side-chains. This isolated beta-hairpin retains the biologically active "canonical conformation" typical of small serine proteinase inhibitor proteins, which explains why it retains inhibitory activity. Since the structural integrity is sequence-inherent and does not depend upon the presence of the remaining protein, this beta-hairpin represents an independent structural motif and so provides a useful model of this type of protein architecture and its relation to biological function. The relationship between the conformation of this beta-hairpin and its biological activity is discussed. |
==About this Structure== | ==About this Structure== | ||
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The Bowman-Birk inhibitor reactive site loop sequence represents an independent structural beta-hairpin motif., Brauer AB, Kelly G, McBride JD, Cooke RM, Matthews SJ, Leatherbarrow RJ, J Mol Biol. 2001 Mar 2;306(4):799-807. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11243789 11243789] | The Bowman-Birk inhibitor reactive site loop sequence represents an independent structural beta-hairpin motif., Brauer AB, Kelly G, McBride JD, Cooke RM, Matthews SJ, Leatherbarrow RJ, J Mol Biol. 2001 Mar 2;306(4):799-807. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11243789 11243789] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Brauer, A | + | [[Category: Brauer, A B.E.]] |
| - | [[Category: Cooke, R | + | [[Category: Cooke, R M.]] |
[[Category: Kelly, G.]] | [[Category: Kelly, G.]] | ||
| - | [[Category: Leatherbarrow, R | + | [[Category: Leatherbarrow, R J.]] |
| - | [[Category: Matthews, S | + | [[Category: Matthews, S J.]] |
| - | [[Category: Mcbride, J | + | [[Category: Mcbride, J D.]] |
[[Category: bowman-birk inhibitor protein mimetic]] | [[Category: bowman-birk inhibitor protein mimetic]] | ||
[[Category: human elastase inhibitor]] | [[Category: human elastase inhibitor]] | ||
[[Category: type vib beta-turn peptide]] | [[Category: type vib beta-turn peptide]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:00:04 2008'' |
Revision as of 11:00, 21 February 2008
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THE BOWMAN-BIRK INHIBITOR REACTIVE SITE LOOP SEQUENCE REPRESENTS AN INDEPENDENT STRUCTURAL BETA-HAIRPIN MOTIF
Overview
We have determined the NMR structure in aqueous solution of a disulphide-cyclised 11-residue peptide that forms a stable beta-hairpin, incorporating a type VIb beta-turn. The structure is found to be extremely well ordered for a short peptide, with the 30 lowest energy simulated annealing structures having an average pairwise r.m.s. deviation of only 0.36 A over the backbone. All but three side-chains adopt distinct conformations, allowing a detailed analysis of their involvement in cross-strand interactions. The peptide sequence analysed originates from a previously reported study, which identified potent inhibitors of human leukocyte elastase from screening a combinatorial peptide library based on the short protein beta-sheet segment that forms the reactive site loop of Bowman-Birk inhibitors. A detailed comparison of the peptide's solution structure with the corresponding region in the whole protein structure reveals a very good correspondence not only for the backbone (r.m.s. deviation approximately 0.7 A) but also for the side-chains. This isolated beta-hairpin retains the biologically active "canonical conformation" typical of small serine proteinase inhibitor proteins, which explains why it retains inhibitory activity. Since the structural integrity is sequence-inherent and does not depend upon the presence of the remaining protein, this beta-hairpin represents an independent structural motif and so provides a useful model of this type of protein architecture and its relation to biological function. The relationship between the conformation of this beta-hairpin and its biological activity is discussed.
About this Structure
1HD9 is a Single protein structure of sequence from [1]. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
The Bowman-Birk inhibitor reactive site loop sequence represents an independent structural beta-hairpin motif., Brauer AB, Kelly G, McBride JD, Cooke RM, Matthews SJ, Leatherbarrow RJ, J Mol Biol. 2001 Mar 2;306(4):799-807. PMID:11243789
Page seeded by OCA on Thu Feb 21 13:00:04 2008
