Phosphoribosylformylglycinamidine synthase

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Phosphoribosylformylglycinamidine synthase
2hs0.jpg
FGAM syntethase II monomer, Thermotoga maritima
Identifiers
EC no. 6.3.5.3
CAS no. 9032-84-2
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
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PMC articles
PubMed articles
NCBI proteins

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

Contents

ATP + N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H2O 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 1T3T, 1VK3, 1VQ3, 2HRU, 2HRY, 2HS0, 2HS3, and 2HS4.

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]

Related Research Articles

<span class="mw-page-title-main">Nucleotide</span> Biological molecules that form the building blocks of nucleic acids

Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

<span class="mw-page-title-main">Formylation</span>

Formylation refers to any chemical processes in which a compound is functionalized with a formyl group (-CH=O). In organic chemistry, the term is most commonly used with regards to aromatic compounds. In biochemistry the reaction is catalysed by enzymes such as formyltransferases.

Phosphoribosylformylglycinamidine cyclo-ligase is the fifth enzyme in the de novo synthesis of purine nucleotides. It catalyzes the reaction to form 5-aminoimidazole ribotide (AIR) from formylglycinamidine-ribonucleotide FGAM. This reaction closes the ring and produces a 5-membered imidazole ring of the purine nucleus (AIR):

Carbamoyl phosphate synthetase (glutamine-hydrolysing) is an enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol. Its systemic name is hydrogen-carbonate:L-glutamine amido-ligase .

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

<span class="mw-page-title-main">GMP synthase</span>

Guanosine monophosphate synthetase, also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.

<span class="mw-page-title-main">Amidophosphoribosyltransferase</span> Mammalian protein found in Homo sapiens

Amidophosphoribosyltransferase (ATase), also known as glutamine phosphoribosylpyrophosphate amidotransferase (GPAT), is an enzyme responsible for catalyzing the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) into 5-phosphoribosyl-1-amine (PRA), using the amine group from a glutamine side-chain. This is the committing step in de novo purine synthesis. In humans it is encoded by the PPAT gene. ATase is a member of the purine/pyrimidine phosphoribosyltransferase family.

<span class="mw-page-title-main">Phosphoribosyl-N-formylglycineamide</span> Chemical compound

Phosphoribosyl-N-formylglycineamide is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from FGAR.

<span class="mw-page-title-main">Ribose-phosphate diphosphokinase</span> Class of enzymes

Ribose-phosphate diphosphokinase is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under EC 2.7.6.1.

In enzymology, a 5-(carboxyamino)imidazole ribonucleotide synthase (EC 6.3.4.18) is an enzyme that catalyzes the chemical reaction

In enzymology, an adenosylcobyric acid synthase (glutamine-hydrolysing) (EC 6.3.5.10) is an enzyme that catalyzes the chemical reaction

In enzymology, an asparaginyl-tRNA synthase (glutamine-hydrolysing) is an enzyme that catalyzes the chemical reaction

In enzymology, a glutaminyl-tRNA synthase (glutamine-hydrolysing) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">NAD+ synthase (glutamine-hydrolysing)</span>

In enzymology, a NAD+ synthase (glutamine-hydrolysing) (EC 6.3.5.1) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Phosphoribosylamine—glycine ligase</span>

Phosphoribosylamine—glycine ligase, also known as glycinamide ribonucleotide synthetase (GARS), (EC 6.3.4.13) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Phosphoribosylaminoimidazolesuccinocarboxamide synthase</span> Class of enzymes

In molecular biology, the protein domain SAICAR synthase is an enzyme which catalyses a reaction to create SAICAR. In enzymology, this enzyme is also known as phosphoribosylaminoimidazolesuccinocarboxamide synthase. It is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">IMP cyclohydrolase</span>

In enzymology, an IMP cyclohydrolase (EC 3.5.4.10) is an enzyme that catalyzes the chemical reaction

In enzymology, a [glutamate—ammonia-ligase] adenylyltransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Phosphoribosylglycinamide formyltransferase</span>

Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2, 2-amino-N-ribosylacetamide 5'-phosphate transformylase, GAR formyltransferase, GAR transformylase, glycinamide ribonucleotide transformylase, GAR TFase, 5,10-methenyltetrahydrofolate:2-amino-N-ribosylacetamide ribonucleotide transformylase) is an enzyme with systematic name 10-formyltetrahydrofolate:5'-phosphoribosylglycinamide N-formyltransferase. This enzyme catalyses the following chemical reaction

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 (18 June 2020). "ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis". Molecular Cell. 78 (6): 1178–1191.e6. doi:10.1016/j.molcel.2020.05.001. PMC   7306006 . 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. doi: 10.1016/S0021-9258(18)64918-X . 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.
  4. Ali, ES; Sahu, U; Villa, E; O'Hara, BP; Gao, P; Beaudet, C; Wood, AW; Asara, JM; Ben-Sahra, I (18 June 2020). "ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis". Molecular Cell. 78 (6): 1178–1191.e6. doi:10.1016/j.molcel.2020.05.001. PMC   7306006 . PMID   32485148.