A number of enzymes that catalyze the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) via a phospho-histidine intermediate have been shown to be structurally related [1,2,3,4]. These enzymes are:

• Pyruvate,orthophosphate dikinase (EC 2.7.9.1) (PPDK). PPDK catalyzes the reversible phosphorylation of pyruvate and phosphate by ATP to PEP and diphosphate. In plants PPDK function in the direction of the formation of PEP, which is the primary acceptor of carbon dioxide in C4 and crassulacean acid metabolism plants. In some bacteria, such as Bacteroides symbiosus, PPDK functions in the direction of ATP synthesis.
• Phosphoenolpyruvate synthase (EC 2.7.9.2) (pyruvate,water dikinase). This enzyme catalyzes the reversible phosphorylation of pyruvate by ATP to form PEP, AMP and phosphate, an essential step in gluconeogenesis when pyruvate and lactate are used as a carbon source.
• Phosphoenolpyruvate-protein phosphatase (EC 2.7.3.9). This is the first enzyme of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), a major carbohydrate transport system in bacteria. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from PEP is transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease.

All these enzymes share the same catalytic mechanism: they bind PEP and transfer the phosphoryl group from it to a histidine residue. The sequence around that residue is highly conserved and can be used as a signature pattern for these enzymes. As a second signature pattern we selected a conserved region in the C-terminal part of the PEP-utilizing enzymes. The biological significance of this region is not yet known.