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| {{STRUCTURE_1in2| PDB=1in2 | SCENE= }} | | {{STRUCTURE_1in2| PDB=1in2 | SCENE= }} |
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| '''Peptide Antagonist of IGFBP1, (i,i+7) Covalently Restrained Analog'''
| | ===Peptide Antagonist of IGFBP1, (i,i+7) Covalently Restrained Analog=== |
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| ==Overview==
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| Highly structured, peptide antagonists of the interaction between insulin-like growth factor 1 (IGF-I) and IGF binding protein 1 (IGFBP-1) have recently been discovered by phage display of naive peptide libraries [Lowman, H. B., et al. (1998) Biochemistry 37, 8870--8878]. We now report a detailed analysis of the features of this turn-helix peptide motif that are necessary for IGFBP-1 binding and structural integrity. Further rounds of phage randomization indicate the importance of residues contributing to a hydrophobic patch on one face of the helix. Alanine-scanning substitutions confirm that the hydrophobic residues are necessary for binding. However, structural analysis by NMR spectroscopy indicates that some of these analogues are less well folded. Structured, high-affinity analogues that lack the disulfide bond were prepared by introducing a covalent constraint between side chains at positions i and i + 7 or i + 8 within the helix. Analogues based on this scaffold demonstrate that a helical conformation is present in the bound state, and that hydrophobic side chains in this helix, and residues immediately preceding it, interact with IGFBP-1. By comparison of alanine scanning data for IGF-I and the turn-helix peptide, we propose a model for common surface features of these molecules that recognize IGFBP-1.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11456486}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11456486 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11456486}} |
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| ==About this Structure== | | ==About this Structure== |
| Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IN2 OCA]. | | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IN2 OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Zobel, K.]] | | [[Category: Zobel, K.]] |
| [[Category: Covalently constrained helix]] | | [[Category: Covalently constrained helix]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:10:32 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 13:34:55 2008'' |
