A Conserved Allosteric Pathway in Tyrosine Kinase Regulation

William M. Marsiglia, Joseph Katigbak, Sijin Zheng, Moosa Mohammadi, Yingkai Zhang, Nathaniel J. Traaseth

Research output: Contribution to journalArticle

Abstract

Marsiglia et al. reveal that the kinase molecular brake is coupled to the DFG motif through an allosteric pathway involving an isoleucine residue that locks the phenylalanine of the DFG motif activation loop in an inactive conformation. Pathogenic mutations that target the molecular brake activate the enzyme by perturbing this allosteric network.

Original languageEnglish (US)
Pages (from-to)1308-1315.e3
JournalStructure
Volume27
Issue number8
DOIs
StatePublished - Aug 6 2019

Fingerprint

Isoleucine
Phenylalanine
Protein-Tyrosine Kinases
Phosphotransferases
Mutation
Enzymes

Keywords

  • allostery
  • FGF receptor
  • NMR spectroscopy
  • pathogenic mutations
  • tyrosine kinases

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

A Conserved Allosteric Pathway in Tyrosine Kinase Regulation. / Marsiglia, William M.; Katigbak, Joseph; Zheng, Sijin; Mohammadi, Moosa; Zhang, Yingkai; Traaseth, Nathaniel J.

In: Structure, Vol. 27, No. 8, 06.08.2019, p. 1308-1315.e3.

Research output: Contribution to journalArticle

Marsiglia, WM, Katigbak, J, Zheng, S, Mohammadi, M, Zhang, Y & Traaseth, NJ 2019, 'A Conserved Allosteric Pathway in Tyrosine Kinase Regulation', Structure, vol. 27, no. 8, pp. 1308-1315.e3. https://doi.org/10.1016/j.str.2019.05.002
Marsiglia, William M. ; Katigbak, Joseph ; Zheng, Sijin ; Mohammadi, Moosa ; Zhang, Yingkai ; Traaseth, Nathaniel J. / A Conserved Allosteric Pathway in Tyrosine Kinase Regulation. In: Structure. 2019 ; Vol. 27, No. 8. pp. 1308-1315.e3.
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