transformylaseIMP

Transformylase-IMP, also known as AICAR transformylase/IMP cyclohydrolase (ATIC in eukaryotes; PurH in many bacteria), is a bifunctional enzyme involved in de novo purine biosynthesis. It catalyzes two sequential reactions on a single polypeptide: first, the AICAR transformylase reaction, which transfers a formyl group from 10-formyltetrahydrofolate to aminoimidazole carboxamide ribonucleotide (AICAR) to form FAICAR; second, the IMP cyclohydrolase reaction, which converts FAICAR to inosine monophosphate (IMP), completing a key late stage of purine nucleotide formation.

In organisms that encode PurH, the enzyme typically comprises two catalytic domains arranged in one polypeptide: an N-terminal AICAR transformylase domain and a C-terminal IMP cyclohydrolase domain. In humans and other eukaryotes, the corresponding enzyme is usually referred to as ATIC. The reactions rely on folate-derived one-carbon units, with 10-formyltetrahydrofolate serving as the formyl donor for the first step.

Localization and genetic context vary: PurH is common in bacteria and archaea, while ATIC is the eukaryotic homolog. The enzyme is cytosolic in most organisms and plays a critical role in the de novo purine biosynthetic pathway, supplying IMP for downstream conversion into adenine and guanine nucleotides.

Clinical and biotechnological relevance stems from its essential function in purine synthesis. Inhibitors targeting PurH/ATIC can disrupt nucleotide production, making the enzyme a point of interest for antimicrobial and anticancer strategies, as well as for studies of folate metabolism and one-carbon transfer reactions.