Figure 6.

N308D mutation alters the local hydrogen bond network. a) In WT SHP2, the side chain of Asn308 forms two hydrogen bonds with Phe285 in the pTyr-loop (colored in yellow). It also forms a hydrogen bond with the conserved Arg501 which, in turn, makes two direct hydrogen bonds with the main chains of Ala461 and Gly462 in the catalytic P-loop (colored in magenta); b) In the N308D mutant, besides the aforementioned hydrogen bonds, Asp308 forms two additional hydrogen bonds with surrounding residues, most notably, a strong hydrogen bond with Thr288 (2.5 Å).