1IN3
Peptide Antagonist of IGFBP1, (i,i+8) Covalently Restrained Analog
Summary for 1IN3
| Entry DOI | 10.2210/pdb1in3/pdb |
| Related | 1gje 1gjf 1gjg 1imw 1in2 |
| Descriptor | IGFBP-1 antagonist, PENTANE (2 entities in total) |
| Functional Keywords | covalently constrained helix, de novo protein, antagonist |
| Total number of polymer chains | 1 |
| Total formula weight | 1677.02 |
| Authors | Skelton, N.J.,Chen, Y.M.,Dubree, N.,Quan, C.,Jackson, D.Y.,Cochran, A.G.,Zobel, K.,Deshayes, K.,Baca, M.,Pisabarro, M.T.,Lowman, H.B. (deposition date: 2001-05-11, release date: 2001-05-30, Last modification date: 2024-11-06) |
| 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 Cited by 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: 11456486DOI: 10.1021/bi0103866 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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