The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis

Biochemistry. 2010 Sep 21;49(37):7972-4. doi: 10.1021/bi100409w.

Abstract

A complex of RON(M1254T) with AMP-PNP and Mg(2+) reveals a substratelike positioning of Tyr1238 as well as likely catalysis-competent placement of the AMP-PNP and Mg(2+) components and indicates a tendency for cis phosphorylation. The structure shows how the oncogenic mutation may cause the constitutive activation and suggests a mechanistic hypothesis for the autophosphorylation of receptor tyrosine kinases.

MeSH terms

  • Adenylyl Imidodiphosphate
  • Phosphorylation
  • Phosphotransferases
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*

Substances

  • Adenylyl Imidodiphosphate
  • Phosphotransferases
  • Receptor Protein-Tyrosine Kinases