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User:SUJesse/Glucose-6-phosphate isomerase

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Not to be confused with D-xylose isomerase.
Glucose-6-phosphate isomerase
Identifiers
EC no.5.3.1.9
CAS no.9001-41-6
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
Bacterial phospho-glucose isomerase C-terminal region
crystal structure of phosphoglucose/phosphomannose isomerase from pyrobaculum aerophilum in complex with fructose 6-phosphate
Identifiers
Symbolbact-PGI_C
PfamPF10432
InterProIPR019490
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Phosphoglucose isomeras
Identifiers
SymbolPGI
PfamPF00342
SCOP21pgi / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Glucose-6-phosphate isomerase (alternatively known as phosphoglucose isomerase or phosphohexose isomerase) is an enzyme that catalyzes the conversion of glucose-6-phosphate into fructose 6-phosphate in the second step of glycolysis.

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

Structure edit

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 edit

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 edit

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 cytoplasm, the protein is involved in glycolysis and gluconeogenesis, while outside the cell it functions as a neurotrophic factor for spinal and sensory neurons. The same protein is also secreted by cancer cells, where it is called autocrine motility factor[6] and stimulates metastasis.[7] Defects in this gene are the cause of nonspherocytic hemolytic anemia and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment.[1]

Glycolysis edit

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 edit

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 edit

Though originially treated as separate proteins, cloning technology demonstrated that PGI is almost identical to the protein neuroleukin. [8]. Neuroleukin is a neurotrophic factor for spinal and sensory neurons. It is found in large amounts in muscle, brain, heart, and kidneys. [9]

Neuroleukin also acts as a lymphokine secreted by T cells stimulated by lectin. It induces immunoglobulin secretion in B cells as part of a response that activates antibody-secreting cells.[10]

Tumor Cell Autocrine Motility Factor edit

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 edit

In some archaea and bacteria glucose-6-phosphate isomerase (PGI) activity occurs via a bifunctional enzyme that also exhibits phosphomannose isomerase (PMI) activity. Though not closely related to eukaryotic PGIs, the bifunctional enzyme is similar enough that the sequence includes the cluster of threonines and serines that forms the sugar phosphate-binding site in conventional PGI. The enzyme is thought to use the same catalytic mechanisms for both glucose ring-opening and isomerisation for the interconversion of glucose 6-phosphate to fructose 6-phosphate.[14]

Clinical significance edit

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 edit

  1. ^ a b "Entrez Gene: GPI glucose phosphate isomerase".
  2. ^ a b Sun YJ, Chou CC, Chen WS, Wu RT, Meng M, Hsiao CD (1999). "The crystal structure of a multifunctional protein: phosphoglucose isomerase/autocrine motility factor/neuroleukin". Proc Natl Acad Sci U S A. 96 (10): 5412–5417. PMC 21873. PMID 10318897. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: PMC format (link) CS1 maint: multiple names: authors list (link)
  3. ^ a b Jeffery CJ, Bahnson BJ, Chien W, Ringe D, Petsko GA (2000). "Crystal structure of rabbit phosphoglucose isomerase, a glycolytic enzyme that moonlights as neuroleukin, autocrine motility factor, and differentiation mediator". Biochemistry. 39 (5): 955–64. doi:10.1021/bi991604m. PMID 10653639. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Read J, Pearce J, Li X, Muirhead H, Chirgwin J, Davies C (2001). "The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia". J Mol Biol. 309 (2): 447–63. doi:10.1006/jmbi.2001.4680. PMID 11371164. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Graham Solomons JT, Zimmerly EM, Burns S, Krishnamurthy N, Swan MK, Krings S, Muirhead H, Chirgwin J, Davies C (2004). "The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening". J Mol Biol. 342 (3): 847–60. doi:10.1016/j.jmb.2004.07.085. PMID 15342241. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Dobashi Y, Watanabe H, Sato Y; et al. (2006). "Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas". J. Pathol. 210 (4): 431–40. doi:10.1002/path.2069. PMID 17029220. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Watanabe H, Takehana K, Date M, Shinozaki T, Raz A (1 July 1996). "Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide". Cancer Res. 56 (13): 2960–3. PMID 8674049.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Chaput M, Claes V, Portetelle D, Cludts I, Cravador A, Burny A, Gras H, Tartar A (1988). "The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase". Nature. 332 (6163): 454–5. doi:10.1038/332454a0. PMID 3352744. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Gurney ME, Heinrich SP, Lee MR, Yin HS (1986). "Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons". Science. 234 (4776): 566–74. doi:10.1126/science.3020690. PMID 3764429. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Gurney ME, Apatoff BR, Spear GT, Baumel MJ, Antel JP, Bania MB, Reder AT (1986). "Neuroleukin: a lymphokine product of lectin-stimulated T cells". Science. 234 (4776): 574–81. PMID 3020690. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ Watanabe H, Takehana K, Date M, Shinozaki T, Raz A (1996). "Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide". Cancer Res. 56 (13): 2960–3. doi:http://cancerres.aacrjournals.org/content/56/13/2960.long. PMID 8674049. {{cite journal}}: Check |doi= value (help); External link in |doi= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Silletti S, Raz A (1993). "Autocrine motility factor is a growth factor". Biochem Biophys Res Commun. 194 (1): 454–5. doi:10.1006/bbrc.1993.1840. PMID 8392842. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ Liotta LA, Mandler R, Murano G, Katz DA, Gordon RK, Chiang PK, Schiffmann E (1986). "Tumor cell autocrine motility factor". Proc Natl Acad Sci U S A. 83 (10): 3302–6. doi:http://cancerres.aacrjournals.org/content/56/13/2960.long. PMID 3085086. {{cite journal}}: Check |doi= value (help); External link in |doi= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Swan MK, Hansen T, Schonheit P, Davies C (2004). "A novel phosphoglucose isomerase (PGI)/phosphomannose isomerase from the crenarchaeon Pyrobaculum aerophilum is a member of the PGI superfamily: structural evidence at 1.16-A resolution". J. Biol. Chem. 279 (38): 39838–45. doi:10.1074/jbc.M406855200. PMID 15252053. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  15. ^ Walker JI, Layton DM, Bellingham AJ, Morgan MJ, Faik P (1993). "DNA sequence abnormalities in human glucose 6-phosphate isomerase deficiency". Hum. Mol. Genet. 2 (3): 327–9. doi:10.1093/hmg/2.3.327. PMID 8499925. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ Kanno H, Fujii H, Hirono A, Ishida Y, Ohga S, Fukumoto Y, Matsuzawa K, Ogawa S, Miwa S (1996). "Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia". Blood. 88 (6): 2321–5. PMID 8822954. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Kugler W, Lakomek M (2000). "Glucose-6-phosphate isomerase deficiency". Baillieres Best Pract. Res. Clin. Haematol. 13 (1): 89–101. PMID 10916680. {{cite journal}}: Unknown parameter |month= ignored (help)
  18. ^ "GPI Deficiency".

Further reading edit

  • Walker JI, Faik P, Morgan MJ (1990). "Characterization of the 5' end of the gene for human glucose phosphate isomerase (GPI)". Genomics. 7 (4): 638–43. doi:10.1016/0888-7543(90)90212-D. PMID 2387591.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Brownstein BH, Silverman GA, Little RD; et al. (1989). "Isolation of single-copy human genes from a library of yeast artificial chromosome clones". Science. 244 (4910): 1348–51. doi:10.1126/science.2544027. PMID 2544027. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  • Mizrachi Y (1989). "Neurotrophic activity of monomeric glucophosphoisomerase was blocked by human immunodeficiency virus (HIV-1) and peptides from HIV-1 envelope glycoprotein". J. Neurosci. Res. 23 (2): 217–24. doi:10.1002/jnr.490230212. PMID 2547084.
  • Gurney ME, Apatoff BR, Spear GT; et al. (1986). "Neuroleukin: a lymphokine product of lectin-stimulated T cells". Science. 234 (4776): 574–81. doi:10.1126/science.3020690. PMID 3020690. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  • Faik P, Walker JI, Redmill AA, Morgan MJ (1988). "Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences". Nature. 332 (6163): 455–7. doi:10.1038/332455a0. PMID 3352745.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Zanella A, Izzo C, Rebulla P; et al. (1981). "The first stable variant of erythrocyte glucose-phosphate isomerase associated with severe hemolytic anemia". Am. J. Hematol. 9 (1): 1–11. doi:10.1002/ajh.2830090102. PMID 7435496. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  • Faik P, Walker JI, Morgan MJ (1994). "Identification of a novel tandemly repeated sequence present in an intron of the glucose phosphate isomerase (GPI) gene in mouse and man". Genomics. 21 (1): 122–7. doi:10.1006/geno.1994.1233. PMID 7545951.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Xu W, Beutler E (1995). "The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia". J. Clin. Invest. 94 (6): 2326–9. doi:10.1172/JCI117597. PMC 330061. PMID 7989588.
  • Xu W, Lee P, Beutler E (1996). "Human glucose phosphate isomerase: exon mapping and gene structure". Genomics. 29 (3): 732–9. doi:10.1006/geno.1995.9944. PMID 8575767.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Baronciani L, Zanella A, Bianchi P; et al. (1996). "Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia". Blood. 88 (6): 2306–10. PMID 8822952. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  • Beutler E, West C, Britton HA; et al. (1998). "Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA)". Blood Cells Mol. Dis. 23 (3): 402–9. doi:10.1006/bcmd.1997.0157. PMID 9446754. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  • Kanno H, Fujii H, Miwa S (1998). "Expression and enzymatic characterization of human glucose phosphate isomerase (GPI) variants accounting for GPI deficiency". Blood Cells Mol. Dis. 24 (1): 54–61. doi:10.1006/bcmd.1998.0170. PMID 9616041.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Kugler W, Breme K, Laspe P; et al. (1998). "Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency". Hum. Genet. 103 (4): 450–4. doi:10.1007/s004390050849. PMID 9856489. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  • Belyaeva OV, Balanovsky OP, Ashworth LK; et al. (1999). "Fine mapping of a polymorphic CA repeat marker on human chromosome 19 and its use in population studies". Gene. 230 (2): 259–66. doi:10.1016/S0378-1119(99)00056-6. PMID 10216265. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  • Yakirevich E, Naot Y (2000). "Cloning of a glucose phosphate isomerase/neuroleukin-like sperm antigen involved in sperm agglutination". Biol. Reprod. 62 (4): 1016–23. doi:10.1095/biolreprod62.4.1016. PMID 10727272.
  • Haga A, Niinaka Y, Raz A (2000). "Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor is a multifunctional phosphoprotein". Biochim. Biophys. Acta. 1480 (1–2): 235–44. PMID 11004567.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links edit

This article incorporates text from the public domain Pfam and InterPro: IPR019490

Category:Protein domains Category:EC 5.3.1 Category:Tumor markers

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