Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2

Pádua R, Sun Y, Marko I, Pitsawong W, Stiller J, Otten R, Kern D, Nature Communications 9(1) (2018) DOI

SASDEN4 – Protein tyrosine phosphatase SHP2

Tyrosine-protein phosphatase non-receptor type 11
MWexperimental 56 kDa
MWexpected 61 kDa
log I(s) 1.21×102 1.21×101 1.21×100 1.21×10-1
Tyrosine-protein phosphatase non-receptor type 11 small angle scattering data  s, nm-1
ln I(s)
Tyrosine-protein phosphatase non-receptor type 11 Guinier plot ln 1.21×102 Rg: 2.7 nm 0 (2.7 nm)-2 s2
(sRg)2I(s)/I(0)
Tyrosine-protein phosphatase non-receptor type 11 Kratky plot 1.104 0 3 sRg
p(r)
Tyrosine-protein phosphatase non-receptor type 11 pair distance distribution function Rg: 2.7 nm 0 Dmax: 8.9 nm

Data validation


Fits and models


log I(s)
 s, nm-1
Tyrosine-protein phosphatase non-receptor type 11 ALLOSMOD model

Synchrotron SAXS data from solutions of Protein tyrosine phosphatase SHP2 in 50 mM ADA, 2 mM TCEP, pH 6.5 were collected on the BL4-2 beam line at the Stanford Synchrotron Radiation Lightsource (SSRL; Stanford, CA, USA) using a Rayonix MX225-HE detector at a sample-detector distance of 1.7 m and at a wavelength of λ = 0.1127 nm (l(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). Solute concentrations ranging between 0.9 and 14.2 mg/ml were measured at 20°C. 10 successive 1 second frames were collected. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted. The low angle data collected at lower concentration were merged with the highest concentration high angle data to yield the final composite scattering curve.

Tyrosine-protein phosphatase non-receptor type 11 (SHP2)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Monomer
Mon. MW   60.9 kDa
 
UniProt   Q06124-2 (1-529)
Sequence   FASTA
 
PDB code   4DGP