The histidine-containing phosphocarrier protein (HPr) is a central component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) [1,2], which transfers metabolic carbohydrates across the cell membrane in many bacterial species. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is as follows: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to Enzyme I (EI) of the PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease complex (enzymes EII/EIII).

HPr [3,4,5] is a small cytoplasmic protein of 70 to 90 amino acid residues. In some bacteria HPr is a domain in a larger protein that includes a EIII(Fru) (IIA) domain (see <PDOC00528>) and in some cases also the EI domain. A conserved histidine in the N-terminal section of HPr serves as an acceptor for the phosphoryl group of EI. In the central part of HPr there is a conserved serine which, in Gram-positive bacteria only, is phosphorylated by an ATP-dependent protein kinase; a process which probably play a regulatory role in sugar transport.

The overall architecture of the HPr domain has been described as an open faced β-sandwich in which a β-sheet is packed against three α-helices (see <PDB:1FU0>). Regulatory phosphorylation at the conserved Ser residue does not appear to induce large structural changes to the HPr domain, in particular in the region of the active site [6,7].

We developed a profile which covers the entire HPr domain. The sequence around both phosphorylation sites are well conserved and can be used as signature patterns for HPr domains.