PROSITE documentation PDOC00391IMP dehydrogenase / GMP reductase signature
IMP dehydrogenase (EC 1.1.1.205) (IMPDH) catalyzes the rate-limiting reaction of de novo GTP biosynthesis, the NAD-dependent reduction of IMP into XMP [1]. Inhibition of IMP dehydrogenase activity results in the cessation of DNA synthesis. As IMP dehydrogenase is associated with cell proliferation, it is a possible target for cancer chemotherapy. Mammalian and bacterial IMPDHs are tetramers of identical chains. There are two IMP dehydrogenase isozymes in humans [2].
GMP reductase (EC 1.7.1.7) catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP [3]. It converts nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and maintains intracellular balance of A and G nucleotides.
IMP dehydrogenase and GMP reductase share many regions of sequence similarity. One of these regions is centered on a cysteine residue thought [3] to be involved in binding IMP. We have used this region as a signature pattern.
Last update:December 2004 / Pattern and text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Collart F.R. Huberman E. |
| Title | Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs. | |
| Source | J. Biol. Chem. 263:15769-15772(1988). | |
| PubMed ID | 2902093 |
| 2 | Authors | Natsumeda Y. Ohno S. Kawasaki H. Konno Y. Weber G. Suzuki K. |
| Title | Two distinct cDNAs for human IMP dehydrogenase. | |
| Source | J. Biol. Chem. 265:5292-5295(1990). | |
| PubMed ID | 1969416 |
| 3 | Authors | Andrews S.C. Guest J.R. |
| Title | Nucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12. | |
| Source | Biochem. J. 255:35-43(1988). | |
| PubMed ID | 2904262 |
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