Ontology highlight
ABSTRACT:
SUBMITTER: LaRochelle JR
PROVIDER: S-EPMC6207684 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
LaRochelle Jonathan R JR Fodor Michelle M Vemulapalli Vidyasiri V Mohseni Morvarid M Wang Ping P Stams Travis T LaMarche Matthew J MJ Chopra Rajiv R Acker Michael G MG Blacklow Stephen C SC
Nature communications 20181030 1
Activating mutations in PTPN11, encoding the cytosolic protein tyrosine phosphatase SHP2, result in developmental disorders and act as oncogenic drivers in patients with hematologic cancers. The allosteric inhibitor SHP099 stabilizes the wild-type SHP2 enzyme in an autoinhibited conformation that is itself destabilized by oncogenic mutations. Here, we report the impact of the highly activated and most frequently observed mutation, E76K, on the structure of SHP2, and investigate the effect of E76 ...[more]