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PDBsum entry 1in2
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References listed in PDB file
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Key reference
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Title
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Structure-Function analysis of a phage display-Derived peptide that binds to insulin-Like growth factor binding protein 1.
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Authors
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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.
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Ref.
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Biochemistry, 2001,
40,
8487-8498.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
79%.
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Abstract
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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 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.
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Secondary reference #1
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Title
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Molecular mimics of insulin-Like growth factor 1 (igf-1) for inhibiting igf-1: igf-Binding protein interactions.
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Authors
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H.B.Lowman,
Y.M.Chen,
N.J.Skelton,
D.L.Mortensen,
E.E.Tomlinson,
M.D.Sadick,
I.C.Robinson,
R.G.Clark.
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Ref.
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Biochemistry, 1998,
37,
8870-8878.
[DOI no: ]
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PubMed id
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