The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) [1,2]
is a major carbohydrate transport system in bacteria. The PTS catalyzes the
phosphorylation of incoming sugar substrates concomitant with their
translocation across the cell membrane. The general mechanism of the PTS is
the following: a phosphoryl group from phosphoenolpyruvate (PEP) is
transferred to enzyme I (EI) of PTS which in turn transfers it to a phosphoryl
carrier protein (HPr) (see <PDOC00318>). Phospho-HPr then transfers the
phosphoryl group to a sugar-specific permease which consists of at least three
structurally distinct domains (IIA, IIB, and IIC),  which can either be
fused together in a single polypeptide chain or exist as two or three
interactive chains, formerly called enzymes II (EII) and III (EIII).
The first domain (IIA) (see <PDOC00528>), carries the first permease-specific
phosphorylation site, an histidine which is phosphorylated by phospho-HPr. The
second domain (IIB) is phosphorylated by phospho-IIA on a cysteinyl or
histidyl residue, depending on the sugar transported. Finally, the phosphoryl
group is transferred from the IIB domain to the sugar substrate concomitantly
with the sugar uptake processed by the IIC domain (see <PDOC51103>). The IIC
domain forms the translocation channel and the specific substrate-binding
site. An additional transmembrane domain IID (see <PDOC51108>), homologous to
IIC, can be found in some PTSs, e.g. for mannose [1,3,4,5,6].
According to structural and sequence analyses, the PTS EIIB domain
(EC 18.104.22.168) can be divided in five groups [7,8,9,10].
- The PTS EIIB type 1 domain, which is found in the Glucose class of PTS, has
an average length of about 80 amino acids. It forms a split α/β
sandwich composed of an antiparallel sheet (β 1 to β 4) and three
α helices superimposed onto one side of the sheet (see <PDB:1IBA>). The
phosphorylation site (Cys) is located at the end of the first β strand
on a protrusion formed by the edge of β 1 and the reverse turn between
β 1 and β 2 .
- The PTS EIIB type 2 domain, which is found in the Mannitol class of PTS,
has an average length of about 100 amino acids. It consists of a four
stranded parallel β sheet flanked by two α helices (α 1 and 3)
on one face and helix α 2 on the opposite face, with a characteristic
Rossmann fold comprising two right-handed β-α-β motifs (see
<PDB:1VKR>). The phosphorylation site (Cys) is located at the N-terminus of
the domain, in the first β strand .
- The PTS EIIB type 3 domain, which is found in the Lactose class of PTS, has
an average length of about 100 amino acids. It is composed of a central
four-stranded parallel open twisted β sheet, which is flanked by three
α helices on the concave side and two on the convex side of the β
sheet (see <PDB:1IIB>). The phosphorylation site (Cys) is located in the
C-terminal end of the first β strand .
- The PTS EIIB type 4 domain, which is found in the Mannose class of PTS, has
an average length of about 160 amino acids. It has a central core of seven
parallel β strands surrounded by a total of six α-helices. Three
helices cover the front face, one the back face with the remaining two
capping the central β sheet at the top and bottom (see <PDB:1NRZ>). The
phosphorylation site (His) is located at the suface exposed loop between
strand 1 and helix 1 .
- The PTS EIIB type 5 domain, which is found in the Sorbitol class of PTS,
has an average length of about 190 amino acids. The phosphorylation site
(Cys) is located in the N-terminus of the domain.
The region around the phosphorylated cysteine of some PTS components is well
conserved and can be used  as a signature pattern for the following IIB
- Arbutin-, cellobiose- and salicin-specific; IIB(Asc).
- β-glucosides-specific; IIB(Bgl).
- Glucose-specific; IIB(Glc).
- N-acetylglucosamine-specific; IIB(Nag).
- Sucrose-specific; IIB(Scr).
- Maltose and glucose-specific (gene malX).
- Trehalose-specific (gene treB).
- Escherichia coli arbutin-like (gene glvB).
- Bacillus subtilis sacX.
A EIIB-like type 2 domain can be found in bacterial transcriptional regulatory
proteins . In these cases, the EIIB-like domain is found in association
with other domains like the DeoR-type HTH domain (see <PDOC00696>) or the PTS
regulatory domain (a transcriptional antiterminator). It may possess a
regulatory function, through its phosphorylation activity, or act as a simple
We have developed a signature pattern for the phosphorylation site of EIIB
domains. We also developed five profiles that cover the entire PTS EIIB
domains. These profiles are directed respectively against Glucose class of
PTS, Mannitol class of PTS, Lactose class of PTS, Mannose class of PTS, and
Sorbitol class of PTS.
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