Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition

Nature Communications

Vidyasiri Vemulapalli¹  Stephen C. Blacklow¹  Jonathan R. LaRochelle¹  Rajiv Chopra²  Matthew J. LaMarche²  Michael G. Acker²  Morvarid Mohseni²  Travis Stams²  Ping Wang²  Michelle Fodor² 

[1] Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School;Novartis Institutes for Biomedical Research;

DOI  :  10.1038/s41467-018-06823-9

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown