<p>The histidine-containing phosphocarrier protein (HPr) is a central component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), which transfers metabolic carbohydrates across the cell membrane in many bacterial species [<cite idref="PUB00003612"/>, <cite idref="PUB00000073"/>]. PTS catalyses 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 the phosphoryl carrier protein (HPr) [<cite idref="PUB00003342"/>, <cite idref="PUB00005243"/>]. Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease complex (enzymes EII/EIII). </p><p>HPr [<cite idref="PUB00004777"/>, <cite idref="PUB00005010"/>] 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 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 beta-sandwich in which a beta-sheet is packed against three alpha-helices. 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 [<cite idref="PUB00025027"/>, <cite idref="PUB00032584"/>].</p> Phosphotransferase system, phosphocarrier HPr protein