Phosphoribosylglycinamide formyltransferase

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

10-formyltetrahydrofolate + N¹-(5-phospho-D-ribosyl)glycinamide ${\displaystyle \rightleftharpoons }$ tetrahydrofolate + N²-formyl-N¹-(5-phospho-D-ribosyl)glycinamide

This THF dependent enzyme catalyzes a nucleophilic acyl substitution of the formyl group from 10-formyltetrahydrofolate (fTHF) to N¹-(5-phospho-D-ribosyl)glycinamide (GAR) to form N²-formyl-N¹-(5-phospho-D-ribosyl)glycinamide (fGAR) as shown above. This reaction plays an important role in the formation of purine through the de novo purine biosynthesis pathway. This pathway creates inosine monophosphate (IMP), a precursor to adenosine monophosphate (AMP) and guanosine monophosphate (GMP). AMP is a building block for important energy carriers such as ATP, NAD⁺ and FAD, and signaling molecules such as cAMP. GARTfase's role in de novo purine biosynthesis makes it a target for anti-cancer drugs and its overexpression during postnatal development has been connected to Down syndrome. There are two known types of genes encoding GAR transformylase in E.coli: purN and purT, while only purN is found in humans. Many residues in the active site are conserved across bacterial, yeast, avian and human enzymes.