Phosphoribosylformylglycinamidine synthase explained

Phosphoribosylformylglycinamidine synthase
Ec Number:	6.3.5.3
Cas Number:	9032-84-2
Go Code:	0004642
Width:	270

In enzymology, a phosphoribosylformylglycinamidine synthase is an enzyme that catalyzes the chemical reaction

ATP + N₂-formyl-N₁-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H₂O

\rightleftharpoons ADP + phosphate + 2-(formamido)-N₁-(5-phospho-D-ribosyl)acetamidine + L-glutamate

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).^{[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,,,,,,, and .

Regulation

This enzyme participates in purine metabolism. Oncogenic and physiological signals lead to the ERK-dependent PFAS phosphorylation at the T619 site, stimulating de novo purine synthesis flux. In addition, ERK-mediated PFAS phosphorylation is required for cell and tumor growth.^[4]

Notes and 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 . ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis . Molecular Cell . 18 June 2020 . 78 . 6 . 1178–1191.e6 . 10.1016/j.molcel.2020.05.001 . 32485148 . 7306006 .
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 . 157 - 62 . 13416226 . 1 . 10.1016/S0021-9258(18)64918-X . free .
3. Web site: Hoffman, R.A. . Matsumoto, K. . Stotz, A. . Andreichuk YuV . Nielsen, I.S. . Paluh, J.L. . ADE6 - phosphoribosylformylglycinamidine synthase . Wikigenes . . 21 October 2019.
4. Ali . ES . Sahu . U . Villa . E . O'Hara . BP . Gao . P . Beaudet . C . Wood . AW . Asara . JM . Ben-Sahra . I . ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis. . Molecular Cell . 18 June 2020 . 78 . 6 . 1178–1191.e6 . 10.1016/j.molcel.2020.05.001 . 32485148. 7306006 .