Biology:Prostacyclin synthase

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Short description: Enzyme found in humans

prostaglandin-I synthase
Cartoon diagram of human prostacyclin synthase. Heme group visible at center. From PDB: 2IAG​
Identifiers
EC number5.3.99.4
CAS number65802-86-0
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Prostaglandin-I synthase (EC 5.3.99.4) also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the PTGIS gene.[1] This enzyme belongs to the family of cytochrome P450 isomerases.

Function

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H2 to prostacyclin (prostaglandin I2), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A2 contribute to the development of myocardial infarction, stroke, and atherosclerosis.[2]

Unlike most P450 enzymes, PGIS does not require molecular oxygen (O2). Instead it uses its heme cofactor to catalyze the isomerization of prostaglandin H2 to prostacyclin. Prostaglandin H2 is produced by cyclooxygenase in the first committed step of prostaglandin biosynthesis.

Nomenclature

The systematic name of this enzyme class is (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate 6-isomerase. Other names in common use include prostacyclin synthase, prostacyclin synthetase, prostagladin I2 synthetase, PGI2 synthase, PGIS, PTGIS, and PGI2 synthetase.

Pathways

Thromboxane synthesis
Eicosanoid synthesis.

Molecular interactions

Generally, protein–protein interactions play crucial roles and are critical for formation of protein microenvironment, cell signaling and direct regulation of the activity of metabolic enzymes. Information on tissue-specific spectrum of molecular interactions of prostacyclin synthase will be useful for subnetwork analysis of PTGIS. Following proteins became known as potential direct binders of PTGIS: CYP2J2, GST, GSTA1, GLRX3, AKR1A1. Protein–protein and protein-peptide interactions were experimentally verified using surface plasmon resonance technology.[3]

See also

  • Prostanoid

References

  1. ↑ "Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization, and promoter activity". Genomics 36 (2): 296–304. September 1996. doi:10.1006/geno.1996.0465. PMID 8812456. 
  2. ↑ "Entrez Gene: PTGIS". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=5740. 
  3. ↑ "Affinity Isolation and Mass Spectrometry Identification of Prostacyclin Synthase (PTGIS) Subinteractome". Biology 8 (2): 49. June 2019. doi:10.3390/biology8020049. PMID 31226805. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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