Tuning a three-component reaction for trapping kinase substrate complexes.

  title={Tuning a three-component reaction for trapping kinase substrate complexes.},
  author={Alexander V Statsuk and Dustin J Maly and Markus A. Seeliger and Miles A. Fabian and William Biggs and David J Lockhart and Patrick P Zarrinkar and John Kuriyan and Kevan M. Shokat},
  journal={Journal of the American Chemical Society},
  volume={130 51},
The upstream protein kinases responsible for thousands of phosphorylation events in the phosphoproteome remain to be discovered. We developed a three-component chemical reaction which converts the transient noncovalent substrate-kinase complex into a covalently cross-linked product by utilizing a dialdehyde-based cross-linker, 1. Unfortunately, the reaction of 1 with a lysine in the kinase active site and an engineered cysteine on the substrate to form an isoindole cross-linked product could… CONTINUE READING