Data from: The pathogenic E139D mutation stabilizes a non-canonical active state of the multi-domain phosphatase SHP2

Dysregulation of the phosphatase SHP2 is implicated in various diseases,
including congenital disorders and cancer. SHP2 contains two
phosphotyrosine-recognition domains (N-SH2 and C-SH2) and a protein
tyrosine phosphatase (PTP) domain. The N-SH2 domain is critical for SHP2
regulation. In the auto-inhibited state, it binds to the PTP domain and
blocks the active site, but phosphoprotein engagement destabilizes the
N-SH2/PTP domain interaction, thereby exposing the active site. Many
disease mutations in SHP2 are at the N-SH2/PTP interface, and they
hyperactivate SHP2 by disrupting auto-inhibitory interactions. The
activating E139D mutation represents an exception to this mechanism, as it
resides in the C-SH2 domain and makes minimal interactions in
auto-inhibited and active state crystal structures. As part of this study,
we used AlphaFold2 modeling and molecular dynamics simulations to
characterize an alternative active conformation of SHP2, in which Glu139
interacts with Arg4 and Arg5 on the N-SH2 domain to stabilize a novel
N-SH2/C-SH2 interface. This dataset includes the molecular dynamics
trajectories for the E139D mutant in this unique active conformation, as
well as Python scripts used to extract select measurements from the
trajectories.