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| 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) |
| Consensus pattern: |
[LIVMT]-[RK]-[LIVM]-G-[LIVM]-G-x-G-[SRK]-[LIVMAT]-C-x-T
C may be the IMP-binding residue |
| Sequences known to belong to this class detected by the pattern: |
ALL |
| Other sequence(s) detected in Swiss-Prot: |
NONE |
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| Matching PDB structures:
1B3O 1EEP 1JCN 1JR1 ... [ALL] |
References:
| 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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