1HD9
The Bowman-Birk Inhibitor Reactive Site Loop Sequence Represents an Independent Structural Beta-Hairpin Motif
Summary for 1HD9
| Entry DOI | 10.2210/pdb1hd9/pdb |
| Descriptor | BOWMAN-BIRK INHIBITOR DERIVED PEPTIDE (1 entity in total) |
| Functional Keywords | peptide inhibitor, bowman-birk inhibitor protein mimetic, human elastase inhibitor, type vib beta-turn peptide, hydrolase inhibitor |
| Biological source | synthetic construct |
| Total number of polymer chains | 1 |
| Total formula weight | 1195.41 |
| Authors | Brauer, A.B.E.,Kelly, G.,McBride, J.D.,Cooke, R.M.,Matthews, S.J.,Leatherbarrow, R.J. (deposition date: 2000-11-13, release date: 2001-03-29, Last modification date: 2024-11-20) |
| Primary citation | Brauer, A.B.E.,Kelly, G.,Mcbride, J.D.,Cooke, R.M.,Matthews, S.J.,Leatherbarrow, R.J. The Bowman-Birk Inhibitor Reactive Site Loop Sequence Represents an Independent Structural Beta-Hairpin Motif J.Mol.Biol., 306:799-, 2001 Cited by PubMed Abstract: 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. PubMed: 11243789DOI: 10.1006/JMBI.2000.4410 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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