1IMW

Peptide Antagonist of IGFBP-1

Summary for 1IMW

• Entry DOI: 10.2210/pdb1imw/pdb
• Related: 1gje 1gjf 1gjg 1in2 1in3
• Descriptor: IGFBP-1 antagonist (1 entity in total)
• Functional Keywords: loop-turn-helix, de novo protein, antagonist
• Total number of polymer chains: 1
• Total formula weight: 1771.09

Authors

Lowman, H.B.,Chen, Y.M.,Skelton, N.J.,Mortensen, D.L.,Tomlinson, E.E.,Sadick, M.D.,Robinson, I.C.,Clark, R.G. (deposition date: 2001-05-11, release date: 2001-05-30, Last modification date: 2011-07-13)

Primary citation

Skelton, N.J.,Chen, Y.M.,Dubree, N.,Quan, C.,Jackson, D.Y.,Cochran, A.,Zobel, K.,Deshayes, K.,Baca, M.,Pisabarro, M.T.,Lowman, H.B.
Structure-function analysis of a phage display-derived peptide that binds to insulin-like growth factor binding protein 1.
Biochemistry, 40:8487-8498, 2001

PubMed Abstract: 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 naïve 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.

PubMed: 11456486
DOI: 10.1021/bi980426e

Experimental method

SOLUTION NMR