Figure 4

Crystal structure of the E139D mutant. a) Crystal structure of the E139D mutant does not display any obvious conformational changes in the C-SH2 (shown in cyan) or PTP domains (shown in green), superimposed on the WT SHP2 structure (colored in grey). Note that the mutant residue E139D is far away from the catalytic cysteine, Cys459 (~40 Å). The N-SH2 domain is shown in blue. b) In the E139D structure, the side chain of Asp139 forms only two hydrogen bonds with the main chain atoms of G115 and His116 (cyan dash lines), whereas in the WT structure, Glu139 forms three hydrogen bonds with His114 and His116 (grey dash lines). The mutation could loosen the connection between the βA and βB strand in C-SH2 domain, thereby exposing the side chain of Arg138, a key residue for pTyr-peptide binding.