Protein-Npi-phosphohistidine---sugar phosphotransferase (type II)
Glucose permease IIA domain functions as part of phosphorylation of sugars, a phosphoryl group is transferred from Hpr to IIA Domain via a histidyl residue then to IIB domain- then finally to a sugar which is being transported into the organism. It is part of the bacterial phosphotransferase system (PTS) phosphorylation cascade. It should be noted that there is very little sequence similarity across the enzymes containing IIA that are specific to different sugars they inevitably transport.
Reference Protein and Structure
- Sequence
-
Q59250
(2.7.1.69)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Bacillus subtilis (Bacteria)
- PDB
-
1gpr
- REFINED CRYSTAL STRUCTURE OF IIA DOMAIN OF THE GLUCOSE PERMEASE OF BACILLUS SUBTILIS AT 1.9 ANGSTROMS RESOLUTION
(1.9 Å)
- Catalytic CATH Domains
-
2.70.70.10
(see all for 1gpr)
Enzyme Reaction (EC:2.7.1.191)
Enzyme Mechanism
Introduction
An associative phosphoryl transfer mechanism is assumed, the P atom passes from a tetrahedron in phospho-HPr, through a trigonal bipyramid in the transition state, to an inverted tetrahedron in phospho-IIAglc. In order to bring the hydrated phosphoryl group of phospho-HPr into the transition state, we assume that hydrogen bonds to water are replaced by H bonds. These hydrogen bonds are presumably optimised to stabilise the transition state, they are likely to be stronger and this in turn should enhance the electrophilicity of the P atom. In turn the H bond from Gly85 to to His83 should make the reactive Nepsilon2 more nucleophilic.
Catalytic Residues Roles
| UniProt | PDB* (1gpr) | ||
| His68 | His68A | Nepsilon-H atom of His68 interacts with Nepsilon atoms of His83, and is ready for hydrogen bonding to the phosphoryl group on His83 in phosphorylated IIAglc. This hydrogen bond may play an important role in stabilising the transition state. | electrostatic stabiliser, polar interaction |
| Thr66 | Thr66A | Hydrogen-bonded to His83. | electrostatic stabiliser, polar interaction |
| His83 | His83A | Participates directly in phosphoryl transfer, accepting a phosphoryl group from HPr and donating to the IIAglc domain. The Nepsilon- H atom of His 83 is hydrogen-bonded to the main chain oxygen of Gly 85. The Nepsilon are available for nucleophilic attack by phospho-HPr. | covalent catalysis, covalently attached, electrostatic stabiliser, polar interaction |
Chemical Components
References
- Pelton JG et al. (1996), J Biol Chem, 271, 33446-33456. Structures of Active Site Histidine Mutants of IIIGlc, a Major Signal-transducing Protein in Escherichia coli: EFFECTS ON THE MECHANISMS OF REGULATION AND PHOSPHORYL TRANSFER. DOI:10.1074/jbc.271.52.33446. PMID:8969208.
- Clore GM et al. (2013), Trends Biochem Sci, 38, 515-530. Structure, dynamics and biophysics of the cytoplasmic protein-protein complexes of the bacterial phosphoenolpyruvate: sugar phosphotransferase system. DOI:10.1016/j.tibs.2013.08.003. PMID:24055245.
- Chen Y et al. (1998), Proteins, 31, 258-270. High‐resolution solution structure of Bacillus subtilis IIAglc. DOI:10.1002/(sici)1097-0134(19980515)31:3<258::aid-prot3>3.3.co;2-q. PMID:9593197.
- Liao DI et al. (1991), Biochemistry, 30, 9583-9594. Structure of the IIA domain of the glucose permease of Bacillus subtilis at 2.2-.ANG. resolution. DOI:10.1021/bi00104a004. PMID:1911744.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| His68A | electrostatic stabiliser |
| His83A | electrostatic stabiliser |
| Thr66A | electrostatic stabiliser, polar interaction |
| His68A | polar interaction |
| His83A | polar interaction, covalent catalysis, covalently attached |
Chemical Components
Catalytic Residues Roles
| Residue | Roles |
|---|