GARTfase's role in de novo purine biosynthesis makes it a target for anti-cancer drugs[6] and its overexpression during postnatal development has been connected to Down syndrome.

[11] 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 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.

A single water molecule possibly held in place by hydrogen bonding with the carboxylate group of the persistent Asp144 residue transfers protons from the GAR-N to the THF-N.

[12][13] Much of the early active site mapping on GAR TFase was determined with the bacterial enzyme owing to the quantity available from its overexpression in E.

[14] Using a bromoacetyl dideazafolate affinity analog James Inglese and colleagues first identified Asp144 as an active site residue likely involved in the formyl transfer mechanism.

Due to their increased growth rate and metabolic requirements, cancer cells rely on de novo nucleotide biosynthesis to achieve levels of AMP and GMP necessary.