Structural mobility of the active site in classical protein tyrosine phosphatases and dual specificity phosphatases

Classical protein tyrosine phosphatases and dual specificity phosphatases share a common structural fold and constitute a major part of the protein tyrosine phosphatase family that dephosphorylate proteins involved in critical cellular processes such as cell growth and differentiation, immune regulation, and brain function. The active site of the enzyme family involves residues in several loops and the conformation of the active site residues and loops are critical in enzyme catalysis. A large number of structural studies have yielded various structures of classical protein tyrosine phosphatases and dual specificity phosphatases, which exhibit mobility of active site residues and loops depending on substrate/ligand binding and regulation states. The mobility is likely to play a role in the catalytic efficiency and cellular regulation processes of the enzymes. In this review article, we analyze currently available structures of classical protein tyrosine phosphatases and dual specificity phosphatases to understand the nature of structural mobility of the enzyme active site and its relationship with enzyme activity and cellular regulation.