FGAM synthetase

The details of the pathway for de novo biosynthesis are shown in Fig. 15-16. The amino acid L-glutamine is the substrate providing nitrogen atoms for reactions 1, 4 and 14, catalyzed by amido phosphoribosyltransferase, FGAM synthetase and GMP synthetase, respectively. Glycine is a substrate at reaction 2, and L-aspartate at reactions 7 and 11. P-Rib-PP is a substrate and activator for amidophosphoribosyltransferase, which is subject to inhibition by AMP. IMP and GMP and by polyglutamate derivatives of dihydrofolate. 

Fig. 15-16 The de novo purine biosynthetic pathway. Rib-5-P, ribose 5-phosphate P-Rib-PP, 5-phosphoribosyl 1-pyrophosphate PRA, 5-phosphoribosylamine IO-CHO-FH4, /Vl0-formyl tetrahydrofolate GAR, glycineamide ribotide FGAR. /V-formylglycineamide ribotide FGAM, /V-formylglycineamidine ribotide AIR, 5-aminoimidazole ribotide CAIR, 4-carboxy-5-aminoimidazole ribotide SAICAR, iV-succino-5-aminoimidazole-4-carboxamide ribotide AICAR, 5-aminoimidazole-4-carboxamide ribotide FAICAR, 5-formamidoimidazole-4-carboxamide ribotide sAMP, /V-succino-AMP. Enzymes (1) amido phosphoribosyltransferase (2) GAR synthetase (3) GAR transformylase (4) FGAM synthetase (5) AIR synthetase (6) AIR carboxylase (7) SAICAR synthetase (8) adenylosuecinase (9) AICAR transformylase (10) IMP cyclohydrolase (11) sAMP synthetase (12) adenylosuecinasc (13) IMP dehydrogenase (14) GMP synthetase.

Figure 13 Cartoon representation of Salmonella typhimurlum IgPurL (1T3T). The N-terminal domain (1-140) is colored green, the linker domain (141-214) is colored yellow, the FGAM synthetase domain (215-979) is colored blue, and the glutaminase domain (980-1295) is colored red. Image rendered in PYMOL.

FGAM synthetase (EC 6.3.5.3) i Formylglycinamidine ribotide (FGAM) ade6 7R... 

There are four multifunctional enzymes in the pathway A trifunctional enzyme comprising GAR synthetase, GAR transformylase and AIR synthetase catalyzes reactions 2, 3 and 5 (PRA—> GAR— FGAR, FGAM > AIR Fig. 15-16), respectively. The GAR synthetase and GAR transformylase domains may be separated by digestion of the trifunctional enzyme with the protease, chymotrypsin. 

---