Folylpolyglutamate synthase (FPGS) is an ATP-dependent enzyme that is responsible for the addition of a polyglutamate tail to folate and folate derivatives []. It plays a key role in the retention of the intracellular folate pool. In some bacteria, such as Escherichia coli, the addition of L-glutamate to dihydropteroate (dihydrofolate synthetase activity) and the subsequent additions of L-glutamate to tetrahydrofolate (FPGS activity) are catalyzed by the same enzyme, FolC [].The crystal structure of the MgATP complex of the enzyme from Lactobacillus casei reveals FPGS to be a modular protein, consisting of two domains, one with a typical mononucleotide-binding fold and the other similar to the folate-binding enzyme dihydrofolate reductase. The active site of the enzyme is located in a large interdomain cleft adjacent to an ATP-binding P-loop motif. Opposite this site, in the C domain, a cavity likely to be the folate binding site has been identified, and inspection of this cavity and the surrounding protein structure suggests that the glutamate tail of the substrate may project into the active site. A further feature of the structure is a well defined Omega loop, which contributes both to the active site and to interdomain interactions [].This entry represents the eukaryotic FPGS enzymes.
Folylpolyglutamate synthase (FPGS) is an ATP-dependent enzyme that is responsible for the addition of a polyglutamate tail to folate and folate derivatives []. It plays a key role in the retention of the intracellular folate pool. In some bacteria, such as Escherichia coli, the addition of L-glutamate to dihydropteroate (dihydrofolate synthetase activity) and the subsequent additions of L-glutamate to tetrahydrofolate (FPGS activity) are catalyzed by the same enzyme, FolC [].The crystal structure of the MgATP complex of the enzyme from Lactobacillus casei reveals FPGS to be a modular protein, consisting of two domains, one with a typical mononucleotide-binding fold and the other similar to the folate-binding enzyme dihydrofolate reductase. The active site of the enzyme is located in a large interdomain cleft adjacent to an ATP-binding P-loop motif. Opposite this site, in the C domain, a cavity likely to be the folate binding site has been identified, and inspection of this cavity and the surrounding protein structure suggests that the glutamate tail of the substrate may project into the active site. A further feature of the structure is a well defined Omega loop, which contributes both to the active site and to interdomain interactions [].This entry represents a conserved site found in the FPGS enzymes.
Folylpolyglutamate synthase (FPGS) is an ATP-dependent enzyme that is responsible for the addition of a polyglutamate tail to folate and folate derivatives []. It plays a key role in the retention of the intracellular folate pool. In some bacteria, such as Escherichia coli, the addition of L-glutamate to dihydropteroate (dihydrofolate synthetase activity) and the subsequent additions of L-glutamate to tetrahydrofolate (FPGS activity) are catalyzed by the same enzyme, FolC [].The crystal structure of the MgATP complex of the enzyme from Lactobacillus casei reveals FPGS to be a modular protein, consisting of two domains, one with a typical mononucleotide-binding fold and the other similar to the folate-binding enzyme dihydrofolate reductase. The active site of the enzyme is located in a large interdomain cleft adjacent to an ATP-binding P-loop motif. Opposite this site, in the C domain, a cavity likely to be the folate binding site has been identified, and inspection of this cavity and the surrounding protein structure suggests that the glutamate tail of the substrate may project into the active site. A further feature of the structure is a well defined Omega loop, which contributes both to the active site and to interdomain interactions [].
