{PDOC00391} {PS00487; IMP_DH_GMP_RED} {BEGIN} *********************************************** * IMP 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. -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. -Last update: December 2004 / Pattern and text revised. [ 1] Collart F.R., Huberman E. "Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs." J. Biol. Chem. 263:15769-15772(1988). PubMed=2902093 [ 2] Natsumeda Y., Ohno S., Kawasaki H., Konno Y., Weber G., Suzuki K. "Two distinct cDNAs for human IMP dehydrogenase." J. Biol. Chem. 265:5292-5295(1990). PubMed=1969416 [ 3] Andrews S.C., Guest J.R. "Nucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12." Biochem. J. 255:35-43(1988). PubMed=2904262 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}