User:SUJesse/Glucose-6-phosphate isomerase

Bacterial phospho-glucose isomerase C-terminal region
crystal structure of phosphoglucose/phosphomannose isomerase from pyrobaculum aerophilum in complex with fructose 6-phosphate
Identifiers
Symbol	bact-PGI_C
Pfam	PF10432
InterPro	IPR019490
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Glucose-6-phosphate isomerase (alternatively known as phosphoglucose isomerase or phosphohexose isomerase) is an

The human variant of this enzyme is encoded by the GPI gene.^[1]

Structure

PGI monomers are made of two domains, one made of two separate segments called the large domain and the other made of the segment in between called the small domain ^[2]. The two domains are each αβα sandwiches, with the small domain containing a five-strand β-sheet surrounded by α-helices while the large domain has a six-stranded β-sheet ^[3]. The large domain and the C-terminal of each monomer also contain "arm-like" protruisions.^[2]

Functional PGI is a dimer composed of two identical monomers. The two monomers interact notably through the two protrusions in a hugging embrace. The active site of each monomer is formed by a cleft between the two domains and the dimer interface.^[3]

Mechanism

The mechanism for PGI uses to interconvert glucose 6-phosphate and fructose 6-phosphate consists of three major steps: opening the glucose ring, isomerizing glucose into fructose through an enediol intermediate, and closing the fructose ring. ^[4]

Glucose 6 phosphate binds to PGI as a hemiacetal ring. The ring is opened in a "push-pull" mechanism by His388, which protonates the C5 oxygen, and Lys518, which deprotonates the C1 hydroxyl group. This creates an open chain aldose. Then, the substrated is rotated about the C3-C4 bond to position it for isomerization. At this point, Glu357 deprotonates C2 to create a cis-enediolate intermediate stabilized by Arg272. To complete the isomerization, Glue357 donates its proton to C1, the C2 hydroxyl group loses its proton and the open-chain ketose, Fructose 6-phosphate is formed. Finally, the ring is closed by rotating the substrate about the C3-C4 bond again and deptrotonating the C5 hydroxyl with Lys518 to cause to the opposite of the ring opening mechanism used to start the reaction.^[5]

Function

This gene belongs to the GPI family whose members encode multifunctional phosphoglucose isomerase proteins involved in energy pathways. The protein encoded by this gene is a dimeric enzyme that catalyzes the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate.

glucose 6-phosphate <=> fructose 6-phosphate

The protein has different functions inside and outside the cell. In the

Glycolysis

α-D-Glucose 6-phosphate	{{{forward_enzyme}}}		β-D-Fructose 6-phosphate
	{{{minor_forward_substrate(s)}}}	{{{minor_forward_product(s)}}}
	[[image:Biochem_reaction_arrow_{{{reaction_direction_(forward/reversible/reverse)}}}_NNNN_horiz_med.svg|75px]]
	Phosphoglucose isomerase

Compound C00668 at KEGG Pathway Database. Enzyme 5.3.1.9 at KEGG Pathway Database. Compound C05345 at KEGG Pathway Database. Reaction R00771 at KEGG Pathway Database.

Isomerization of glucose

D-Glucose	{{{forward_enzyme}}}		D-Fructose
	{{{minor_forward_substrate(s)}}}	{{{minor_forward_product(s)}}}
	[[image:Biochem_reaction_arrow_{{{reaction_direction_(forward/reversible/reverse)}}}_NNNN_horiz_med.svg|75px]]
	Phosphoglucose isomerase

Neuroleukin

Though originially treated as separate proteins, cloning technology demonstrated that PGI is almost identical to the protein neuroleukin.

Cloning experiments also revealed that PGI is identical to the protein known as autocrine motility factor.[11] Autocrine motility factor produced and secreted by cancer cells and stimulates cell growth and motility as a growth factor. ^[12] Autocrine motility factor is thought to play a key role in cancer metastasis. ^[13]

Prokaryotic bifunctional glucose-6-phosphate isomerase

In some

A deficiency of phosphoglucose isomerase is responsible for 4% of the hemolytic anemias due to glycolytic enzyme deficiencies.^[15][16][17]

Several cases of glucose phosphate isomerase deficiency have recently been identified.^[18]

References