Summary

In bacteria and eukaryotes the last two reactions of the de novo purine biosynthetic pathway for IMP biosynthesis are sequentially catalyzed by a bifunctional enzyme containing aminoimidazole carboxamide ribonucleotide (AICAR) transformylase and IMP cyclohydrolase activities. To date, much of the biochemical and structural characterization has been done on the enzyme from organisms other than E. coli (see for example [Wolan04, Axelrod08]).

In E. coli early studies suggested an association between AICAR transformylase and IMP cyclohydrolase [Gots69]. Later studies concluded that AICAR transformylase and IMP cyclohydrolase form a bifunctional enzyme with both activities residing on a single polypeptide [Aiba89, Flannigan90]. Complementation studies suggested that the N-terminal domain contains the IMP cyclohydrolase activity and the C-terminal domain contains the AICAR transformylase activity [Aiba89]. More recently recombinant, N-terminally His₆-tagged enzyme from E. coli has been expressed, purified, crystallized, and subjected to preliminary X-ray diffraction analysis [Qiu11].

The transformylation reaction is the second of two such reactions in the de novo biosynthesis of purine nucleotides. Like the glycinamide ribonucleotide (GAR) transformylase, AICAR transformylase also utilizes 10-formyl-tetrahydrofolate as the formyl donor. The synthesis of IMP in both E. coli and Salmonella enterica subsp. enterica serovar Typhimurium is under the control of a common regulatory protein, the product of the purR gene [Flannigan90]. The final step in IMP biosynthesis is the ring closure of 5-formylamino-4-imidazolecarboxamide-ribonucleotide (FAICAR) to form IMP which is the first complete purine nucleotide.

Review: [Zhang08]

Additional Citations: [Peterson91]