PROSITE documentation PDOC00391

IMP dehydrogenase / GMP reductase signature




Description

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.

Technical section

PROSITE method (with tools and information) covered by this documentation:

IMP_DH_GMP_RED, PS00487; IMP dehydrogenase / GMP reductase signature  (PATTERN)


References

1AuthorsCollart F.R., Huberman E.
TitleCloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs.
SourceJ. Biol. Chem. 263:15769-15772(1988).
PubMed ID2902093

2AuthorsNatsumeda Y., Ohno S., Kawasaki H., Konno Y., Weber G., Suzuki K.
TitleTwo distinct cDNAs for human IMP dehydrogenase.
SourceJ. Biol. Chem. 265:5292-5295(1990).
PubMed ID1969416

3AuthorsAndrews S.C., Guest J.R.
TitleNucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12.
SourceBiochem. J. 255:35-43(1988).
PubMed ID2904262



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