Figure 1. Role of protein phosphatases in intracellular signalling. The phosphorylation state of proteins is regulated by kinases and phosphatases that respectively attach phosphate to or remove phosphate from specific residues in the context of short amino acid motifs. Phosphorylated amino acids serve as binding sites for noncatalytic domains (SH2, for example) of proteins that mediate downstream signalling through other distinct structures (grey boxes).

Figure 2. Active-site features and catalytic mechanisms of protein phosphatases. (a) Hydrogen-bond coordination (dashed lines) of the active-site residues, metal ions and water molecules (OH^–, W2, W3) in the serine/threonine phosphatase PP2B. (Adapted from Kissinger et al., 1995). Substrate phosphoryl groups are hydrolysed via a single-step reaction involving a metal-activated water molecule. (b) Model of the active site of Yersinia protein tyrosine phosphatase. (Adapted from Stuckey et al., 1994). A phosphoenzyme intermediate is formed by nucleophilic attack of the catalytic cysteine thiolate (Step 1) on substrate phosphotyrosine (pTyr), which is subsequently hydrolysed upon nucleophilic attack of an activated water molecule (Step 2). The catalytic arginine (Arg) hydrogen-bonds with the equatorial oxygens of the substrate phosphoryl group to position it for attack and stabilize transition-state intermediates.