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PDBsum entry 1in2
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Antagonist PDB id
1in2

 

 

 

 

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Contents
Protein chain
16 a.a.
Ligands
LNK
PDB id:
1in2
Name: Antagonist
Title: Peptide antagonist of igfbp1, (i,i+7) covalently restrained analog
Structure: Igfbp-1 antagonist. Chain: a. Engineered: yes. Other_details: (i,i+7) locked helix variant of bp1-01
Source: Synthetic: yes. Other_details: the peptide was chemically synthesized. It was designed from sequence selected from a phage display library.
NMR struc: 20 models
Authors: N.J.Skelton,Y.M.Chen,N.Dubree,C.Quan,D.Y.Jackson,A.G.Cochran,K.Zobel, K.Deshayes,M.Baca,M.T.Pisabarro,H.B.Lowman
Key ref:
N.J.Skelton et al. (2001). Structure-function analysis of a phage display-derived peptide that binds to insulin-like growth factor binding protein 1. Biochemistry, 40, 8487-8498. PubMed id: 11456486 DOI: 10.1021/bi0103866
Date:
11-May-01     Release date:   30-May-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 15 a.a.
Key:    Secondary structure

 

 
DOI no: 10.1021/bi0103866 Biochemistry 40:8487-8498 (2001)
PubMed id: 11456486  
 
 
Structure-function analysis of a phage display-derived peptide that binds to insulin-like growth factor binding protein 1.
N.J.Skelton, Y.M.Chen, N.Dubree, C.Quan, D.Y.Jackson, A.Cochran, K.Zobel, K.Deshayes, M.Baca, M.T.Pisabarro, H.B.Lowman.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20170129 S.L.Deutscher (2010).
Phage display in molecular imaging and diagnosis of cancer.
  Chem Rev, 110, 3196-3211.  
19748896 E.F.Lee, A.Fedorova, K.Zobel, M.J.Boyle, H.Yang, M.A.Perugini, P.M.Colman, D.C.Huang, K.Deshayes, and W.D.Fairlie (2009).
Novel Bcl-2 homology-3 domain-like sequences identified from screening randomized peptide libraries for inhibitors of the pro-survival Bcl-2 proteins.
  J Biol Chem, 284, 31315-31326.  
16547350 M.P.Del Borgo, R.A.Hughes, R.A.Bathgate, F.Lin, K.Kawamura, and J.D.Wade (2006).
Analogs of insulin-like peptide 3 (INSL3) B-chain are LGR8 antagonists in vitro and in vivo.
  J Biol Chem, 281, 13068-13074.  
16470897 T.Shi, S.M.Spain, and D.L.Rabenstein (2006).
A striking periodicity of the cis/trans isomerization of proline imide bonds in cyclic disulfide-bridged peptides.
  Angew Chem Int Ed Engl, 45, 1780-1783.  
16138387 C.Borghouts, C.Kunz, and B.Groner (2005).
Current strategies for the development of peptide-based anti-cancer therapeutics.
  J Pept Sci, 11, 713-726.  
16233816 F.Uchiyama, Y.Tanaka, Y.Minari, and N.Tokui (2005).
Designing scaffolds of peptides for phage display libraries.
  J Biosci Bioeng, 99, 448-456.  
15742332 M.P.Del Borgo, R.A.Hughes, and J.D.Wade (2005).
Conformationally constrained single-chain peptide mimics of relaxin B-chain secondary structure.
  J Pept Sci, 11, 564-571.  
15380039 F.De Ceuninck, A.Caliez, L.Dassencourt, P.Anract, and P.Renard (2004).
Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes.
  Arthritis Res Ther, 6, R393-R403.  
14624865 S.Lien, and H.B.Lowman (2003).
Therapeutic peptides.
  Trends Biotechnol, 21, 556-562.  
12512072 S.S.Sidhu, W.J.Fairbrother, and K.Deshayes (2003).
Exploring protein-protein interactions with phage display.
  Chembiochem, 4, 14-25.  
11983338 K.Deshayes, M.L.Schaffer, N.J.Skelton, G.R.Nakamura, S.Kadkhodayan, and S.S.Sidhu (2002).
Rapid identification of small binding motifs with high-throughput phage display: discovery of peptidic antagonists of IGF-1 function.
  Chem Biol, 9, 495-505.
PDB code: 1lb7
12501157 R.L.Rich, and D.G.Myszka (2002).
Survey of the year 2001 commercial optical biosensor literature.
  J Mol Recognit, 15, 352-376.  
12417739 S.K.Sia, P.A.Carr, A.G.Cochran, V.N.Malashkevich, and P.S.Kim (2002).
Short constrained peptides that inhibit HIV-1 entry.
  Proc Natl Acad Sci U S A, 99, 14664-14669.
PDB code: 1gzl
11839484 W.L.DeLano (2002).
Unraveling hot spots in binding interfaces: progress and challenges.
  Curr Opin Struct Biol, 12, 14-20.  
11738175 A.G.Cochran (2001).
Protein-protein interfaces: mimics and inhibitors.
  Curr Opin Chem Biol, 5, 654-659.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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