1in2

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Peptide Antagonist of IGFBP1, (i,i+7) Covalently Restrained Analog

Structural highlights

1in2 is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:ACE, LNK, NH2
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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.

Structure-function analysis of a phage display-derived peptide that binds to insulin-like growth factor binding protein 1.,Skelton NJ, Chen YM, Dubree N, Quan C, Jackson DY, Cochran A, Zobel K, Deshayes K, Baca M, Pisabarro MT, Lowman HB Biochemistry. 2001 Jul 24;40(29):8487-98. PMID:11456486[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. Skelton NJ, Chen YM, Dubree N, Quan C, Jackson DY, Cochran A, Zobel K, Deshayes K, Baca M, Pisabarro MT, Lowman HB. Structure-function analysis of a phage display-derived peptide that binds to insulin-like growth factor binding protein 1. Biochemistry. 2001 Jul 24;40(29):8487-98. PMID:11456486

Contents


PDB ID 1in2

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