Editing PEP group translocation (section)

== Mechanism ==
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'''), [[Phosphocarrier protein|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.<ref name="Biology of Prokaryotes">{{cite book |last1=Lengeler |first1=Joseph W. | last2 = Drews | first2 = Gerhard | last3 = Schlegel | first3 = Hans G. | name-list-style = vanc |title=Biology of Prokaryotes |publisher=Blackwell Science |year=1999 |location=Stuttgart, Germany | pages =83–84 | isbn=978-0-632-05357-5}}</ref>
[[File:Phosphotransferase system.svg|thumb|400x400px|The glucose PTS system in ''[[Escherichia coli|E. coli]]'' and ''[[Bacillus subtilis|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 [[Saccharide transporter|transmembrane enzyme II C]] ('''EIIC'''), forming [[glucose-6-phosphate]].<ref name="Biology of Prokaryotes"/> The benefit of transforming glucose into glucose-6-phosphate is that it will not leak out of the cell, therefore providing a one-way concentration gradient of glucose. The HPr is common to the phosphotransferase systems of the other substrates mentioned earlier, as is the upstream EI.<ref>{{cite book | vauthors = Madigan MT, Martinko JM, Dunlap PV, Clark DP | title = Brock biology of microorganisms | edition = 12th | location = San Francisco, CA | publisher = Pearson/Benjamin Cummings | date = 2009 }}</ref>

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.<ref name=":0" />

===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.

[[File:Phosphotransferase system Serratia marcescens.png|400px|thumb|In ''[[Serratia marcescens]]''.]]