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We are deeply saddened by the passing of Amos Bairoch (1957–2025), the creator of PROSITE. We wish to dedicate our latest paper, published shortly before his death, to him. He will always be a source of inspiration to us.
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Amos Bairoch

PROSITE documentation PDOC00157
Glucose-6-phosphate isomerase (GPI) family signatures and profile


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PURL: https://purl.expasy.org/prosite/documentation/PDOC00157

Description

Glucose-6-phosphate isomerase (GPI) (EC 5.3.1.9) or phosphoglucose isomerase (PGI) [1,2] is a dimeric enzyme that catalyzes the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. PGI is involved in different pathways: in most higher organisms it is involved in glycolysis; in mammals it is involved in gluconeogenesis; in plants in carbohydrate biosynthesis; in some bacteria it provides a gateway for fructose into the Entner-Doudouroff pathway. Besides it's role as a glycolytic enzyme, mammalian PGI can function as a tumor-secreted cytokine and an angiogenic factor (AMF) that stimulates endothelial cell motility. Mammalian PGI is also neuroleukin [3], a neurotrophic factor which supports the survival of various types of neurons.

The sequence of PGI is conserved among diverse species ranging from bacteria to mammals and structures form a similar fold (see <PDB:1IAT>) [4,5], comprised of two subdomains that each form an α-β-α sandwich, with the active site located in the cleft between the subdomains and on the dimer interface. A glutamate and a lysine residue as well as a histidine from the other protomer in the dimer are implicated in the catalytic mechanism. The structure resembles that of the SIS domain (see <PDOC51464>).

As signature patterns for this enzyme we selected two conserved regions, the first region is located in the central section of PGI, while the second one is located in its C-terminal section. We also developed a profile that covers the entire PGI.

Last update:

September 2009 / Text revised; profile added.

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Technical section

PROSITE methods (with tools and information) covered by this documentation:

P_GLUCOSE_ISOMERASE_3, PS51463; Glucose-6-phosphate isomerase family profile  (MATRIX)

P_GLUCOSE_ISOMERASE_1, PS00765; Phosphoglucose isomerase signature 1  (PATTERN)

P_GLUCOSE_ISOMERASE_2, PS00174; Phosphoglucose isomerase signature 2  (PATTERN)


References

1AuthorsAchari A. Marshall S.E. Muirhead H. Palmieri R.H. Noltmann E.A.
TitleGlucose-6-phosphate isomerase.
SourcePhilos. Trans. R. Soc. Lond., B, Biol. Sci. 293:145-157(1981).
PubMed ID6115414

2AuthorsSmith M.W. Doolittle R.F.
TitleAnomalous phylogeny involving the enzyme glucose-6-phosphate isomerase.
SourceJ. Mol. Evol. 34:544-545(1992).
PubMed ID1593646

3AuthorsFaik P. Walker J.I.H. Redmill A.A.M. Morgan M.J.
TitleMouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences.
SourceNature 332:455-457(1988).
PubMed ID3352745
DOI10.1038/332455a0

4AuthorsRead J. Pearce J. Li X. Muirhead H. Chirgwin J. Davies C.
TitleThe crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia.
SourceJ. Mol. Biol. 309:447-463(2001).
PubMed ID11371164
DOI10.1006/jmbi.2001.4680

5AuthorsYamamoto H. Miwa H. Kunishima N.
TitleCrystal structure of glucose-6-phosphate isomerase from Thermus thermophilus HB8 showing a snapshot of active dimeric state.
SourceJ. Mol. Biol. 382:747-762(2008).
PubMed ID18675274
DOI10.1016/j.jmb.2008.07.041



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