Editing PEP group translocation

{{short description|Bacterial metabolic pathway}}
'''PEP (phosphoenol pyruvate) group translocation''', also known as the '''phosphotransferase system''' or '''PTS''', is a distinct method used by [[bacteria]] for sugar uptake where the source of energy is from [[phosphoenolpyruvate]] (PEP). It is known to be a multicomponent system that always involves enzymes of the [[plasma membrane]] and those in the [[cytoplasm]].

The PTS system uses active transport. After the translocation across the membrane, the metabolites transported are modified. The PTS system was discovered by [[Saul Roseman]] in 1964.<ref>{{cite journal | vauthors = Bramley HF, Kornberg HL | title = Sequence homologies between proteins of bacterial phosphoenolpyruvate-dependent sugar phosphotransferase systems: identification of possible phosphate-carrying histidine residues | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 14 | pages = 4777–80 | date = July 1987 | pmid = 3299373 | pmc = 305188 | doi = 10.1073/pnas.84.14.4777 | bibcode = 1987PNAS...84.4777B | doi-access = free }}</ref> The bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) transports and phosphorylates its sugar substrates in a single energy-coupled step. This transport process is dependent on several cytoplasmic phosphoryl transfer proteins - Enzyme I (I), HPr, Enzyme IIA (IIA), and Enzyme IIB (IIB)) as well as the integral membrane sugar permease (IIC).The PTS Enzyme II complexes are derived from independently evolving 4 PTS Enzyme II complex superfamilies, that include the (1) [[PTS-GFL superfamily|Glucose (Glc)]], (2) [[PTS Mannose-Fructose-Sorbose Family|Mannose (Man)]],<ref>{{Cite journal|last1=Liu|first1=Xueli|last2=Zeng|first2=Jianwei|last3=Huang|first3=Kai|last4=Wang|first4=Jiawei|date=2019-06-17|title=Structure of the mannose transporter of the bacterial phosphotransferase system|journal=Cell Research|doi=10.1038/s41422-019-0194-z|issn=1748-7838|pmid=31209249|pmc=6796895|volume=29|issue=8|pages=680–682}}</ref><ref>{{Cite journal|last1=Huang|first1=Kai|last2=Zeng|first2=Jianwei|last3=Liu|first3=Xueli|last4=Jiang|first4=Tianyu|last5=Wang|first5=Jiawei|date=2021-04-06|title=Structure of the mannose phosphotransferase system (man-PTS) complexed with microcin E492, a pore-forming bacteriocin|journal=Cell Discovery|volume=7|issue=1|pages=20|doi=10.1038/s41421-021-00253-6|issn=2056-5968|pmc=8021565|pmid=33820910}}</ref> (3) [[Permease of phosphotransferase system|Ascorbate-Galactitol (Asc-Gat)]]<ref>{{cite journal | vauthors = Luo P, Yu X, Wang W, Fan S, Li X, Wang J | title = Crystal structure of a phosphorylation-coupled vitamin C transporter | journal = Nature Structural & Molecular Biology | volume = 22 | issue = 3 | pages = 238–41 | date = March 2015 | pmid = 25686089 | doi = 10.1038/nsmb.2975 | s2cid = 9955621 }}</ref><ref>{{cite journal | vauthors = Luo P, Dai S, Zeng J, Duan J, Shi H, Wang J | title = Inward-facing conformation of l-ascorbate transporter suggests an elevator mechanism | journal = Cell Discovery | volume = 4 | pages = 35 | date = 2018 | pmid = 30038796 | pmc = 6048161 | doi = 10.1038/s41421-018-0037-y }}</ref> and (4) Dihydroxyacetone (DHA) superfamilies.<ref>{{cite journal|vauthors=Saier MH|title=The Bacterial Phosphotransferase System: New frontiers 50 years after its discovery|journal=Journal of Molecular Microbiology and Biotechnology|volume=25|issue=2-3|pages=73-78|year=2015|pmid=26159069|pmc=4512285|doi=10.1159/000381215|doi-access=free}}</ref><ref>{{cite journal|vauthors=Bächler C, Schneider P, Bähler P, Lustig A, Erni B|title=Escherichia coli dihydroxyacetone kinase controls gene expression by binding to transcription factor DhaR|journal=The EMBO Journal|volume=24|issue=2|pages=283-293|pmid=15616579|year=2005|pmc=545809|doi=10.1038/sj.emboj.7600517|doi-access=free}}</ref>

== Specificity ==
The phosphotransferase system is involved in transporting many sugars into bacteria, including [[glucose]], [[mannose]], [[fructose]] and [[cellobiose]]. '''PTS''' sugars can differ between bacterial groups, mirroring the most suitable carbon sources available in the environment every group evolved. In ''[[Escherichia coli]]'', there are 21 different transporters (i.e. IIC proteins, sometimes fused to IIA and/or IIB proteins, see figure) which determine import specificity. Of these, 7 belong to the fructose (Fru) family, 7 belong to the glucose (Glc) family, and 7 belong to the other PTS permease families.<ref>{{cite journal | vauthors = Tchieu JH, Norris V, Edwards JS, Saier MH | title = The complete phosphotransferase system in Escherichia coli | journal = Journal of Molecular Microbiology and Biotechnology | volume = 3 | issue = 3 | pages = 329–46 | date = July 2001 | pmid = 11361063 }}</ref>

== 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]]''.]]

== Structural analysis ==
Three-dimensional structures of examples of all the soluble, cytoplasmic complexes of the PTS were solved by [[G. Marius Clore]] using multidimensional [[NMR]] spectroscopy, and led to significant insights into how [[signal transduction]] proteins recognize multiple, structurally dissimilar partners by generating similar binding surfaces from completely different structural elements, making use of large binding surfaces with intrinsic redundancy, and exploiting side chain conformational plasticity.<ref name=":0">{{cite journal | vauthors = Clore GM, Venditti V | title = Structure, dynamics and biophysics of the cytoplasmic protein-protein complexes of the bacterial phosphoenolpyruvate: sugar phosphotransferase system | journal = Trends in Biochemical Sciences | volume = 38 | issue = 10 | pages = 515–30 | date = October 2013 | pmid = 24055245 | pmc = 3831880 | doi = 10.1016/j.tibs.2013.08.003 }}</ref>

== References ==

{{reflist}}

== External links ==
* {{MeshName|Phosphoenolpyruvate+Sugar+Phosphotransferase+System}}

{{Multienzyme complexes}}

[[Category:Enzymes]]