Q506 is necessary to position and activate a water molecule for hydrolysis of the phospho-enzyme intermediate (wild type). The Q506P mutant loses this functionality. Q506 also forms two important hydrogen bonds with Asn58 and Ala72 from the N-SH2 domain (colored in blue), which connect the N-SH2 domain to the PTP domain (colored in green). In the Q506P structure, these connections no longer are present. The P-loop (458–464) is highlighted in magenta.