The
phosphoryl group on PEP is eventually transferred to the imported sugar via several proteins. The phosphoryl group is transferred to the
Enzyme E I (
EI),
Histidine Protein (
HPr,
Heat-stable Protein) and
Enzyme E II (
EII) to a conserved
histidine residue, whereas in the Enzyme E II B (
EIIB) the phosphoryl group is usually transferred to a
cysteine residue and rarely to a histidine.
and B. subtilis. The pathway can be read from right to left, with glucose entering the cell and having a phosphate group transferred to it by EIIB. The mannose PTS in E. coli
has the same overall structure as the B. subtilis'' glucose PTS, i.e. the IIABC domains are fused into one protein. In the process of glucose PTS transport specific of
enteric bacteria,
PEP transfers its phosphoryl to a histidine residue on
EI. EI in turn transfers the phosphate to HPr. From HPr the phosphoryl is transferred to
EIIA. EIIA is specific for glucose and it further transfers the phosphoryl group to a
juxtamembrane EIIB. Finally, EIIB phosphorylates glucose as it crosses the plasma membrane through the
transmembrane enzyme II C (
EIIC), forming
glucose-6-phosphate. Proteins downstream of HPr tend to vary between the different sugars. The transfer of a phosphate group to the substrate once it has been imported through the membrane transporter prevents the transporter from recognizing the substrate again, thus maintaining a concentration gradient that favours further import of the substrate through the transporter.
Specificity In many bacteria, there are four different sets of IIA, IIB, and IIC proteins, each specific for a particular sugar (glucose, mannitol, mannose, and lactose/chitobiose). To make things more complicated, IIA may be fused to IIB to form a single protein with 2 domains, or IIB may be fused to IIC (the transporter), also with 2 domains.
Regulation With the glucose phosphotransferase system, the phosphorylation status of
EIIA can have regulatory functions. For example, at low glucose concentrations phosphorylated EIIA accumulates and this activates membrane-bound
adenylate cyclase. Intracellular
cyclic AMP levels rise and this then activates
CAP (
catabolite activator protein), which is involved in the
catabolite repression system, also known as glucose effect. When the glucose concentration is high, EIIA is mostly dephosphorylated and this allows it to inhibit
adenylate cyclase,
glycerol kinase,
lactose permease, and
maltose permease. Thus, in addition to being an efficient way to import substrates into the bacterium, the PEP group translocation system also links this transport to regulation of other relevant proteins. ''. == Structural analysis ==