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August 21, 2006Proceedings of the National Academy of SciencesOpen Access

Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins

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Population

N- and C-terminal domain fragments of IGFBP4 and IGF1, and C-terminal domain fragment of IGFBP1

Design

Preclinical

Authors

TSTomasz SitarGPGrzegorz M. PopowiczISIgor Siwanowicz

Discussion

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Overview

May guide IGFBP variant design for IGF inhibition; extends mechanistic insights but leaves open clinical translation.

Structured PICO

P
Population
N- and C-terminal domain fragments of IGFBP4 and IGF1, and C-terminal domain fragment of IGFBP1
I
Intervention
X-ray crystallography of ternary and binary complexes
O
Outcome
Three-dimensional structures and mechanisms of IGF signaling regulation via IGFBP binding

The structural determination of IGFBP/IGF complexes reveals the mechanism of IGF signaling regulation, supporting the design of IGFBP variants as therapeutic IGF inhibitors.

Cite This Study

Sitar et al. (2006) studied this question.

synapsesocial.com/papers/6a771d0bdf493903fd1eadcahttps://doi.org/10.1073/pnas.0605652103
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Identification and molecular cloning of two new 30-kDa insulin-like growth factor binding proteins isolated from adult human serum1991 · 107 citations
  2. 2Mutants of human insulin-like growth factor I with reduced affinity for the type 1 insulin-like growth factor receptor1988 · 108 citations
  3. 3Structure-Function Analysis of the Human Insulin-like Growth Factor Binding Protein-41998 · 90 citations
  4. 4Cumulative Mutagenesis of the Basic Residues in the 201–218 Region of Insulin-Like Growth Factor (IGF)-Binding Protein-5 Results in Progressive Loss of Both IGF-I Binding and Inhibition of IGF-I Biological Action2005 · 20 citations
  5. 5Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding protein-2: mapping the binding surfaces by nuclear magnetic resonance2005 · 28 citations