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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5473
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pubmed:dateCreated |
2000-6-28
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Human Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/JAK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Library,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Somatotropin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
288
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2042-5
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10856217-Amino Acid Sequence,
pubmed-meshheading:10856217-Animals,
pubmed-meshheading:10856217-Binding Sites,
pubmed-meshheading:10856217-Cell Division,
pubmed-meshheading:10856217-Cell Line,
pubmed-meshheading:10856217-Human Growth Hormone,
pubmed-meshheading:10856217-Imidazoles,
pubmed-meshheading:10856217-Janus Kinase 2,
pubmed-meshheading:10856217-Ligands,
pubmed-meshheading:10856217-Mice,
pubmed-meshheading:10856217-Molecular Sequence Data,
pubmed-meshheading:10856217-Peptide Library,
pubmed-meshheading:10856217-Phosphorylation,
pubmed-meshheading:10856217-Protein Binding,
pubmed-meshheading:10856217-Protein-Tyrosine Kinases,
pubmed-meshheading:10856217-Proto-Oncogene Proteins,
pubmed-meshheading:10856217-Receptors, Somatotropin,
pubmed-meshheading:10856217-Signal Transduction,
pubmed-meshheading:10856217-Structure-Activity Relationship,
pubmed-meshheading:10856217-Transfection
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pubmed:year |
2000
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pubmed:articleTitle |
Designing small-molecule switches for protein-protein interactions.
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pubmed:affiliation |
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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