Ligand-gated split-kinases

Karla Camacho-Soto, Javier Castillo-Montoya, Blake Tye, Indraneel Ghosh

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The activity of protein kinases are naturally gated by a variety of physiochemical inputs, such as phosphorylation, metal ions, and small molecules. In order to design protein kinases that can be gated by user-defined inputs, we describe a sequence dissimilarity based approach for identifying sites in protein kinases that accommodate 25-residue loop insertion while retaining catalytic activity. We further demonstrate that the successful loop insertion mutants provide guidance for the dissection of protein kinases into two fragments that cannot spontaneously assemble and are thus inactive but can be converted into ligand-gated catalytically active split-protein kinases. We successfully demonstrate the feasibility of this approach with Lyn, Fak, Src, and PKA, which suggests potential generality.

Original languageEnglish (US)
Pages (from-to)3995-4002
Number of pages8
JournalJournal of the American Chemical Society
Volume136
Issue number10
DOIs
StatePublished - Mar 12 2014

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Protein Kinases
Phosphotransferases
Ligands
Proteins
Dissection
Phosphorylation
Metal ions
Catalyst activity
Metals
Ions
Molecules

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry
  • Medicine(all)

Cite this

Camacho-Soto, K., Castillo-Montoya, J., Tye, B., & Ghosh, I. (2014). Ligand-gated split-kinases. Journal of the American Chemical Society, 136(10), 3995-4002. https://doi.org/10.1021/ja4130803

Ligand-gated split-kinases. / Camacho-Soto, Karla; Castillo-Montoya, Javier; Tye, Blake; Ghosh, Indraneel.

In: Journal of the American Chemical Society, Vol. 136, No. 10, 12.03.2014, p. 3995-4002.

Research output: Contribution to journalArticle

Camacho-Soto, K, Castillo-Montoya, J, Tye, B & Ghosh, I 2014, 'Ligand-gated split-kinases', Journal of the American Chemical Society, vol. 136, no. 10, pp. 3995-4002. https://doi.org/10.1021/ja4130803
Camacho-Soto K, Castillo-Montoya J, Tye B, Ghosh I. Ligand-gated split-kinases. Journal of the American Chemical Society. 2014 Mar 12;136(10):3995-4002. https://doi.org/10.1021/ja4130803
Camacho-Soto, Karla ; Castillo-Montoya, Javier ; Tye, Blake ; Ghosh, Indraneel. / Ligand-gated split-kinases. In: Journal of the American Chemical Society. 2014 ; Vol. 136, No. 10. pp. 3995-4002.
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