Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) and Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) (IMPDH1, IMPDH2)

Inosine-5'-monophosphate dehydrogenase 1 and 2 are closely related enzymes that catalyze the NAD+-dependent oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), which is the first and rate-limiting step in the de novo biosynthesis of guanine nucleotides. These enzymes are essential for the maintenance of intracellular guanine nucleotide pools and are crucial for nucleic acid synthesis, cell proliferation, and signal transduction. IMPDH is a validated therapeutic target in transplant medicine (as an immunosuppressant), oncology, virology, and anti-parasitic therapy due to its central role in nucleotide biosynthesis; specific inhibitors can suppress cell proliferation or viral replication. Structural studies reveal a characteristic (β/α)8 barrel catalytic domain, and each isoform includes a Bateman domain (CBS domains), which may regulate nucleotide binding or enzyme localization. IMPDHs also display non-catalytic, "moonlighting" activities, such as nucleic acid binding and modulation of gene expression under some conditions.

Other names

IMP dehydrogenase 1IMP dehydrogenase 2IMPDH type IIMPDH type IIInosine monophosphate dehydrogenase 1Inosine monophosphate dehydrogenase 2

Competitive inhibition of active site to block GTP/guanine nucleotide synthesis, resulting in inhibition of DNA/RNA synthesis and cell proliferation (immunosuppressive, antiviral, anticancer actions)