Phosphoribosylformylglycinamidine synthase

In enzymology, a phosphoribosylformylglycinamidine synthase (EC 6.3.5.3) is an enzyme that catalyzes the chemical reaction

ATP + N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H2O ADP + phosphate + 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine + L-glutamate
phosphoribosylformylglycinamidine synthase
FGAM syntethase II monomer, Thermotoga maritima
Identifiers
EC number6.3.5.3
CAS number9032-84-2
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

The 4 substrates of this enzyme are ATP, N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide, L-glutamine, and H2O, whereas its 4 products are ADP, phosphate, 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine, and L-glutamate.

This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds carbon-nitrogen ligases with glutamine as amido-N-donor. The systematic name of this enzyme class is N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide:L-glutamine amido-ligase (ADP-forming). Other names in common use include phosphoribosylformylglycinamidine synthetase, formylglycinamide ribonucloetide amidotransferase, phosphoribosylformylglycineamidine synthetase, FGAM synthetase, FGAR amidotransferase, 5'-phosphoribosylformylglycinamide:L-glutamine amido-ligase, (ADP-forming), 2-N-formyl-1-N-(5-phospho-D-ribosyl)glycinamide:L-glutamine, and amido-ligase (ADP-forming). This enzyme participates in purine metabolism. The results of a recent study indicate that the ERK2 signaling activated by growth and oncogenic signals leads to PFAS phosphorylation at the T619 site. In addition, ERK2-mediated PFAS phosphorylation is required for cell and tumor growth.[1][2]

It is known as ADE6 in Saccharomyces cerevisiae (budding yeast) genetics. [3]

Structural studies

As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes 1T3T, 1VK3, 1VQ3, 2HRU, 2HRY, 2HS0, 2HS3, and 2HS4.

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References
  1. Ali, Eunus S.; Sahu, Umakant; Villa, Elodie; O’Hara, Brendan P.; Gao, Peng; Beaudet, Cynthia; Wood, Antony W.; Asara, John M.; Ben-Sahra, Issam (1 June 2020). "ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis". Molecular Cell. 78: 1–14. doi:10.1016/j.molcel.2020.05.001. ISSN 1097-2765. PMID 32485148.
  2. MELNICK I, BUCHANAN JM (1957). "Biosynthesis of the purines. XIV. Conversion of (alpha-N-formyl) glycinamide ribotide to (alpha-N-formyl) glycinamidine ribotide purification and requirements of the enzyme system". J. Biol. Chem. 225 (1): 157–62. PMID 13416226.
  3. Matsumoto, K.; Stotz, A.; Andreichuk YuV; Nielsen, I.S.; Paluh, J.L.; Hoffman, R.A. "ADE6 - phosphoribosylformylglycinamidine synthase". Wikigenes. Pubmed. Retrieved 21 October 2019.


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