Fig. 4.

(A) Cartoon representation of the surrounding of the N-SH2 domain in the crystal structure of autoinhibited SHP2 (PDB ID 4DGP) (16). The PTP domain belonging to the same protein chain is colored in white. Other protein replicas, interacting with the central N-SH2 domain (colored in tan), are depicted respectively in blue, purple, green, and pink. (B) Correlation between the N-SH2 binding cleft opening, $d_{\text{cleft}}$ (Gly⁶⁷ C$\alpha$–Lys⁸⁹ C$\alpha$ distance) and the N-SH2 blocking loop distance from the catalytic PTP loop, $d_{\text{block}}$ (Asp⁶¹ C$\alpha$–Ala⁴⁶¹ C$\alpha$ distance), as taken from crystal structures of autoinhibited SHP2, comprising either wild type or functional mutants (16, 37, 49, 50).