DB code: T00258

RLCP classification	3.105.250000.90 : Transfer
CATH domain	-.-.-.- :
	3.40.50.- : Rossmann fold
	3.40.930.10 : Mannitol-specific EII; Chain A	Catalytic domain
E.C.	2.7.1.69 2.7.1.-
CSA
M-CSA
MACiE

CATH domain	Related DB codes (homologues)
3.40.930.10 : Mannitol-specific EII; Chain A	S00420

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Includes	RefSeq	Pfam
P00550	PTS system mannitol-specific EIICBA component	EIICBA-Mtl EII-Mtl	Mannitol permease IIC component PTS system mannitol-specific EIIC component Mannitol-specific phosphotransferase enzyme IIB component EC 2.7.1.69 PTS system mannitol-specific EIIB component Mannitol-specific phosphotransferase enzyme IIA component EC 2.7.1.- PTS system mannitol-specific EIIA component	NP_418056.1 (Protein) NC_000913.2 (DNA/RNA sequence) YP_491835.1 (Protein) NC_007779.1 (DNA/RNA sequence)	PF00359 (PTS_EIIA_2) PF02378 (PTS_EIIC) PF02302 (PTS_IIB) [Graphical View]

KEGG enzyme name
protein-Npi-phosphohistidine---sugar phosphotransferase (EC 2.7.1.69 ) glucose permease (EC 2.7.1.69 ) PTS permease (EC 2.7.1.69 ) phosphotransferase, phosphohistidinoprotein-hexose (EC 2.7.1.69 ) enzyme IIl4ac (EC 2.7.1.69 ) gene glC proteins (EC 2.7.1.69 ) gene bglC RNA formation factors (EC 2.7.1.69 ) PEP-dependent phosphotransferase enzyme II (EC 2.7.1.69 ) PEP-sugar phosphotransferase enzyme II (EC 2.7.1.69 ) phosphoenolpyruvate-sugar phosphotransferase enzyme II (EC 2.7.1.69 ) phosphohistidinoprotein-hexose phosphotransferase (EC 2.7.1.69 ) phosphohistidinoprotein-hexose phosphoribosyltransferase (EC 2.7.1.69 ) phosphoprotein factor-hexose phosophotransferase (EC 2.7.1.69 ) protein, specific or class, gene bglC (EC 2.7.1.69 ) ribonucleic acid formation factor, gene glC (EC 2.7.1.69 ) sucrose phosphotransferase system II (EC 2.7.1.69 ) protein-Npi-phosphohistidine:sugar N-pros-phosphotransferase (EC 2.7.1.69 ) protein-Npi-phosphohistidine:sugar Npi-phosphotransferase (EC 2.7.1.69 )

KEGG enzyme name

protein-Npi-phosphohistidine---sugar phosphotransferase
(EC 2.7.1.69 )
glucose permease
(EC 2.7.1.69 )
PTS permease
(EC 2.7.1.69 )
phosphotransferase, phosphohistidinoprotein-hexose
(EC 2.7.1.69 )
enzyme IIl4ac
(EC 2.7.1.69 )
gene glC proteins
(EC 2.7.1.69 )
gene bglC RNA formation factors
(EC 2.7.1.69 )
PEP-dependent phosphotransferase enzyme II
(EC 2.7.1.69 )
PEP-sugar phosphotransferase enzyme II
(EC 2.7.1.69 )
phosphoenolpyruvate-sugar phosphotransferase enzyme II
(EC 2.7.1.69 )
phosphohistidinoprotein-hexose phosphotransferase
(EC 2.7.1.69 )
phosphohistidinoprotein-hexose phosphoribosyltransferase
(EC 2.7.1.69 )
phosphoprotein factor-hexose phosophotransferase
(EC 2.7.1.69 )
protein, specific or class, gene bglC
(EC 2.7.1.69 )
ribonucleic acid formation factor, gene glC
(EC 2.7.1.69 )
sucrose phosphotransferase system II
(EC 2.7.1.69 )
protein-Npi-phosphohistidine:sugar N-pros-phosphotransferase
(EC 2.7.1.69 )
protein-Npi-phosphohistidine:sugar Npi-phosphotransferase
(EC 2.7.1.69 )

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P00550	PTM3C_ECOLI	Protein EIIA N(pi)-phospho-L-histidine + protein EIIB = protein EIIA + protein EIIB N(pi)-phospho-L- histidine/cysteine. Protein EIIB N(pi)-phospho-L- histidine/cysteine + sugar = protein EIIB + sugar phosphate.	Homodimer.	Cell inner membrane, Multi-pass membrane protein.

KEGG Pathways
Map code	Pathways	E.C.
MAP00010	Glycolysis / Gluconeogenesis	2.7.1.69
MAP00051	Fructose and mannose metabolism	2.7.1.69
MAP00052	Galactose metabolism	2.7.1.69
MAP00053	Ascorbate and aldarate metabolism	2.7.1.69
MAP00500	Starch and sucrose metabolism	2.7.1.69
MAP00530	Aminosugars metabolism	2.7.1.69

Compound table
	Substrates			Products			Intermediates
KEGG-id	C04261	C11477	C02743	C00615	C00934	L00031
E.C.	2.7.1.69 2.7.1.-	2.7.1.69	2.7.1.-	2.7.1.69 2.7.1.-	2.7.1.69	2.7.1.-
Compound	Protein N(pi)-phospho-L-histidine	Sugar	Protein cysteine	Protein histidine	Sugar phosphate	Protein S-phosphoryl-cysteine
Type	aromatic ring (with nitrogen atoms),peptide/protein,phosphate group/phosphate ion	polysaccharide	peptide/protein,sulfhydryl group	aromatic ring (with nitrogen atoms),peptide/protein	phosphate group/phosphate ion,polysaccharide	peptide/protein,phosphate group/phosphate ion,sulfide group
ChEBI
PubChem

1a3aA	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1a3aB	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1a3aC	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1a3aD	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
Swiss-prot

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1a3aA	ARG 49;HIS 65;HIS 111		HIS 65 (phosphorylated)
1a3aB	ARG 49;HIS 65;HIS 111		HIS 65 (phosphorylated)
1a3aC	ARG 49;HIS 65;HIS 111		HIS 65 (phosphorylated)
1a3aD	ARG 49;HIS 65;HIS 111		HIS 65 (phosphorylated)

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[2]	Fig.7, Fig.8, p.385	2
[3]	Fig.3

References
[1]
Resource
Comments
Medline ID
PubMed ID	1946374
Journal	Proc Natl Acad Sci U S A
Year	1991
Volume	88
Pages	9603-7
Authors	Sugiyama JE, Mahmoodian S, Jacobson GR
Title	Membrane topology analysis of Escherichia coli mannitol permease by using a nested-deletion method to create mtlA-phoA fusions.
Related PDB
Related UniProtKB	P00550
[2]
Resource
Comments
Medline ID
PubMed ID	9551558
Journal	Structure
Year	1998
Volume	6
Pages	377-88
Authors	van Montfort RL, Pijning T, Kalk KH, Hangyi I, Kouwijzer ML, Robillard GT, Dijkstra BW
Title	The structure of the Escherichia coli phosphotransferase IIAmannitol reveals a novel fold with two conformations of the active site.
Related PDB	1a3a
Related UniProtKB	P00550
[3]
Resource
Comments
Medline ID
PubMed ID	9636714
Journal	J Mol Biol
Year	1998
Volume	279
Pages	245-55
Authors	Bordo D, van Monfort RL, Pijning T, Kalk KH, Reizer J, Saier MH Jr, Dijkstra BW
Title	The three-dimensional structure of the nitrogen regulatory protein IIANtr from Escherichia coli.
Related PDB	1a6j
Related UniProtKB	P69829

Comments
This enzyme is composed of three domains: The N-terminal domain for Mannitol permease IIC component, a domain for Mannitol-specific phosphotransferase enzyme IIB component (E.C. 2.7.1.69), and the C-terminal domain for Mannitol-specific phosphotransferase enzyme IIA component (E.C. 2.7.1.-). The same E.C. number (2.7.1.69) appears in S00297, D00527, S00283, S00046. All of them are enzymes in PTS system. In the phosphotransferase (PTS) system, a phosphoryl group is transferred from phosphoenolpyruvate (PEP) via the PTS enzymes, EI, HPr, IIA, IIB to the tranported sugar. The enzyme here is IIA subunit of a mannitol transporter (IIA-mannitol). His65 (1a3a) is phosphorylated during the phosphotransfer reaction. A phosphoryl transfer between two PTS proteins involves an in-line attack of the phosphorus atom by the acceptor protein. A trigonal bipyramidal transition state is formed with a pentavalent coordination of the phosphorus atom. Productive breakdown of the transition state results in an inversion of the configuration at the phosphorus atom [2]. Although there is no biochemical evidence for the roles of Arg49/His111 (1a3a), Arg49 is ideally positioned to stabilize the transition state in the phosphoryl transfer from HPr to IIA-mannitol. In contrast, whilst His111 is pointed away from the phosphorylation site for HPr, it might also be needed for the phosphoryl transfer to IIB-mannitol.

Comments

This enzyme is composed of three domains: The N-terminal domain for Mannitol permease IIC component, a domain for Mannitol-specific phosphotransferase enzyme IIB component (E.C. 2.7.1.69), and the C-terminal domain for Mannitol-specific phosphotransferase enzyme IIA component (E.C. 2.7.1.-).
The same E.C. number (2.7.1.69) appears in S00297, D00527, S00283, S00046. All of them are enzymes in PTS system.
In the phosphotransferase (PTS) system, a phosphoryl group is transferred from phosphoenolpyruvate (PEP) via the PTS enzymes, EI, HPr, IIA, IIB to the tranported sugar. The enzyme here is IIA subunit of a mannitol transporter (IIA-mannitol).
His65 (1a3a) is phosphorylated during the phosphotransfer reaction. A phosphoryl transfer between two PTS proteins involves an in-line attack of the phosphorus atom by the acceptor protein. A trigonal bipyramidal transition state is formed with a pentavalent coordination of the phosphorus atom. Productive breakdown of the transition state results in an inversion of the configuration at the phosphorus atom [2]. Although there is no biochemical evidence for the roles of Arg49/His111 (1a3a), Arg49 is ideally positioned to stabilize the transition state in the phosphoryl transfer from HPr to IIA-mannitol. In contrast, whilst His111 is pointed away from the phosphorylation site for HPr, it might also be needed for the phosphoryl transfer to IIB-mannitol.

Created	Updated
2002-08-30	2009-03-04