Phosphoribosylamine—glycine ligase, also known as glycinamide ribonucleotide synthetase (GARS), (EC 6.3.4.13) is an enzyme that catalyzes the chemical reaction which is the second step in purine biosynthesis.

[1] In yeast, GARS is part of a bifunctional enzyme (encoded by the ADE5/7 gene) in conjunction with phosphoribosylformylglycinamidine cyclo-ligase (AIRS).

In higher eukaryotes, including humans,[2] GARS is part of a trifunctional enzyme in conjunction with AIRS and with phosphoribosylglycinamide formyltransferase (GART),[3] forming GARS-AIRS-GART.

Then, the nitrogen of PRA attacks the carbonyl carbon in the intermediate, and phosphate leaves, forming GAR.

The overall structure of the enzyme, based on crystallization from E. coli,[7] consists of 16 alpha helices which connect to 20 beta strands by turns and loops.

[9] Among the amino acids that are identical in B. subtilis, S. cerevisiae, D. melanogaster, and D. pseudobscura, almost a third are glycine and proline, which suggests that they play an important role in proper folding of the protein.

[4] In humans, the gene that codes for GARS-AIRS-GART is on chromosome 21, and individuals with Down Syndrome have higher purine levels, which has been correlated with mental retardation.