1in2: Difference between revisions

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[[Image:1in2.jpg|left|200px]]<br /><applet load="1in2" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1in2.jpg|left|200px]]<br /><applet load="1in2" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1in2" />

'''Peptide Antagonist of IGFBP1, (i,i+7) Covalently Restrained Analog'''<br />

==Overview==

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.

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.

==About this Structure==

1IN2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with ACE, NH2 and LNK as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1IN2 OCA].

1IN2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene>, <scene name='pdbligand=NH2:'>NH2</scene> and <scene name='pdbligand=LNK:'>LNK</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IN2 OCA].

==Reference==

Line 13:

[[Category: Protein complex]]

[[Category: Baca, M.]]

[[Category: Chen, Y.M.]]

[[Category: Chen, Y M.]]

[[Category: Cochran, A.G.]]

[[Category: Cochran, A G.]]

[[Category: Deshayes, K.]]

[[Category: Dubree, N.]]

[[Category: Jackson, D.Y.]]

[[Category: Jackson, D Y.]]

[[Category: Lowman, H.B.]]

[[Category: Lowman, H B.]]

[[Category: Pisabarro, M.T.]]

[[Category: Pisabarro, M T.]]

[[Category: Quan, C.]]

[[Category: Skelton, N.J.]]

[[Category: Skelton, N J.]]

[[Category: Zobel, K.]]

[[Category: ACE]]

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[[Category: covalently constrained helix]]

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@@ Line 1: / Line 1: @@
-[[Image:1in2.jpg|left|200px]]<br /><applet load="1in2" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1in2.jpg|left|200px]]<br /><applet load="1in2" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1in2" />
 '''Peptide Antagonist of IGFBP1, (i,i+7) Covalently Restrained Analog'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-IN2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with ACE, NH2 and LNK as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IN2 OCA].
+IN2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene>, <scene name='pdbligand=NH2:'>NH2</scene> and <scene name='pdbligand=LNK:'>LNK</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IN2 OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Protein complex]]
 [[Category: Baca, M.]]
-[[Category: Chen, Y.M.]]
+[[Category: Chen, Y M.]]
-[[Category: Cochran, A.G.]]
+[[Category: Cochran, A G.]]
 [[Category: Deshayes, K.]]
 [[Category: Dubree, N.]]
-[[Category: Jackson, D.Y.]]
+[[Category: Jackson, D Y.]]
-[[Category: Lowman, H.B.]]
+[[Category: Lowman, H B.]]
-[[Category: Pisabarro, M.T.]]
+[[Category: Pisabarro, M T.]]
 [[Category: Quan, C.]]
-[[Category: Skelton, N.J.]]
+[[Category: Skelton, N J.]]
 [[Category: Zobel, K.]]
 [[Category: ACE]]
@@ Line 28: / Line 28: @@
 [[Category: covalently constrained helix]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 22:15:06 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:13:29 2008''