Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) (IMPDH2)

Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) is a purine biosynthetic enzyme that catalyzes the rate-limiting step in de novo guanine nucleotide synthesis, converting IMP to XMP in an NAD+-dependent oxidation reaction.[1][2] IMPDH2 is a critical regulator of intracellular guanine nucleotide pools, which are essential for DNA and RNA synthesis, cell proliferation, and immune function.[1] The enzyme is predominantly expressed in proliferating cells and neoplastic tissues, making it an attractive therapeutic target for cancer and autoimmune diseases.[1] IMPDH2 uniquely exhibits allosteric regulation through adenine and guanine nucleotide binding to its Bateman domain, and can reversibly self-assemble into filaments that modulate sensitivity to feedback inhibition during periods of high metabolic demand.[3] Under proliferative signaling conditions with elevated IMP levels, IMPDH2 filaments resist GTP-mediated inhibition, allowing sustained guanine nucleotide production.[3] This sophisticated regulatory mechanism, combined with its central role in controlling nucleotide pools for rapidly dividing cells, positions IMPDH2 as a valuable target for selective immunosuppression and anticancer therapy.[1]

Other names

Inosine monophosphate dehydrogenase 2IMP dehydrogenaseIMPDH

Catalyzes NAD+-dependent oxidation of inosine-5'-monophosphate (IMP) to xanthosine-5'-monophosphate (XMP) - First committed and rate-limiting step in de novo guanine nucleotide biosynthesis - Allosteric regulation through adenine and guanine nucleotide feedback inhibition - Filament assembly reduces sensitivity to GTP-mediated feedback inhibition during proliferative states