Activating mutations of the non-receptor protein tyrosine phosphatase SHP2 can cause cancer. Here the authors present the crystal structure of SHP2E76K, the most frequent cancer-associated SHP2 mutation, which adopts an open-state structure and show that the allosteric inhibitor SHP099 can revert SHP2E76K to its closed, autoinhibited conformation.
- Jonathan R. LaRochelle
- Michelle Fodor
- Stephen C. Blacklow
