In humans, GARTfase is part of trifunctional enzyme which also includes glycinamide ribnucleotide synthase (GARS)  and aminoimidazole ribonucleotide synthetase (AIRS).
This protein (110kDa) catalyzes steps 2, 3 and 5 of de novo purine biosynthesis.
The proximity of these enzyme units and flexibility of the protein serves to increase pathway throughput.
GARTfase is located on the C-terminal end of the protein.

Human GARTfase has been crystallized by vapor-diffusion sitting drop method and imaged at the Stanford Synchrotron Radiation Laboratory (SSRL) by at least two groups.

The structure can be described by two subdomains which are connected by a seven-stranded beta sheet.
The N- terminal domain consists of a Rossman type mononucleotide fold, with a four strand part of the beta sheet surrounded on each side by two alpha helices.
The beta sheet continues into the C terminal domain, where on one side it is covered by a long alpha helix and on the other it is partially exposed to solvent.
It is the cleft between the two subdomains where the active site lies.

The cleft consists of the GAR binding site and the folate binding pocket.
The folate binding pocket is delineated by pteridine-binding cleft, the formyl transfer region and the benzoylglutamate region which  bind thepteridine head and a benzoylglutamate tail connected by a formyl bound nitrogen of  fTHF.
This folate binding region has been the subject of much research because its inhibition by small molecules has led to the discovery of antineoplastic drugs.
The folate binding loop has been shown to change conformation depending on the pH of solution and as such Human GAR transformylase shows highest activity around pH 7.5-8.
Lower pH (~4.2) conditions change the conformation of the substrate (GAR) binding loops as well.
In humans, GARTfase is part of trifunctional enzyme which also includes glycinamide ribnucleotide synthase (GARS)  and aminoimidazole ribonucleotide synthetase (AIRS). This protein (110kDa) catalyzes steps 2, 3 and 5 of de novo purine biosynthesis. The proximity of these enzyme units and flexibility of the protein serves to increase pathway throughput. GARTfase is located on the C-terminal end of the protein.
Human GARTfase has been crystallized by vapor-diffusion sitting drop method and imaged at the Stanford Synchrotron Radiation Laboratory (SSRL) by at least two groups.
The structure can be described by two subdomains which are connected by a seven-stranded beta sheet. The N- terminal domain consists of a Rossman type mononucleotide fold, with a four strand part of the beta sheet surrounded on each side by two alpha helices. The beta sheet continues into the C terminal domain, where on one side it is covered by a long alpha helix and on the other it is partially exposed to solvent. It is the cleft between the two subdomains where the active site lies.
The cleft consists of the GAR binding site and the folate binding pocket. The folate binding pocket is delineated by pteridine-binding cleft, the formyl transfer region and the benzoylglutamate region which  bind thepteridine head and a benzoylglutamate tail connected by a formyl bound nitrogen of  fTHF. This folate binding region has been the subject of much research because its inhibition by small molecules has led to the discovery of antineoplastic drugs. The folate binding loop has been shown to change conformation depending on the pH of solution and as such Human GAR transformylase shows highest activity around pH 7.5-8. Lower pH (~4.2) conditions change the conformation of the substrate (GAR) binding loops as well.
Phosphoribosylglycinamide formyltransferase