Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Designing small-molecule switches for protein-protein interactions

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Guo, Z. H.
  • Zhou, D. M.
  • Schultz, Peter

publication date

  • June 2000

journal

  • Science  Journal

abstract

  • Mutations introduced into human growth hormone (hGH) (Thr175 --> Gly-hGH) and the extracellular domain of the hGH receptor (Trp104 --> Gly-hGHbp) created a cavity at the protein-protein interface that resulted in binding affinity being reduced by a factor of 10(6). A small library of indole analogs was screened for small molecules that bind the cavity created by the mutations and restore binding affinity. The ligand 5-chloro-2-trichloromethylimidazole was found to increase the affinity of the mutant hormone for its receptor more than 1000-fold. Cell proliferation and JAK2 phosphorylation assays showed that the mutant hGH activates growth hormone signaling in the presence of added ligand. This approach may allow other protein-protein and protein-nucleic acid interactions to be switched on or off by the addition or depletion of exogenous small molecules.

subject areas

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Division
  • Cell Line
  • Human Growth Hormone
  • Imidazoles
  • Janus Kinase 2
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Peptide Library
  • Phosphorylation
  • Protein Binding
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Receptors, Somatotropin
  • Signal Transduction
  • Structure-Activity Relationship
  • Transfection
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.288.5473.2042

PubMed ID

  • 10856217
scroll to property group menus

Additional Document Info

start page

  • 2042

end page

  • 2045

volume

  • 288

issue

  • 5473

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support