IMP dehydrogenase

IMP dehydrogenase
Structure of IMPDH[1]
Identifiers
EC number	1.1.1.205
CAS number	9028-93-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

IMP dehydrogenase EC 1.1.1.205 (Inosine-5'-monophosphate dehydrogenase) (Inosinic acid dehydrogenaseis) (IMPDH) an enzyme that converts inosine monophosphate to xanthosine monophosphate:^[2][3][4][5]

inosine 5'-phosphate + NAD⁺ + H₂O $\rightleftharpoons$ xanthosine 5'-phosphate + NADH + H⁺

It catalyzes the rate-limiting reaction of de novo GTP biosynthesis.^[6]

IMP dehydrogenase is associated with cell proliferation and is a possible target for cancer chemotherapy. Mammalian and bacterial IMPDHs are tetramers of identical chains. There are two IMP dehydrogenase isozymes in humans.^[7] IMP dehydrogenase nearly always contains a long insertion that has two CBS domains within it.

The structure of this enzyme is composed of a TIM barrel domain with two CBS domains inserted within a loop.^[1][4]

It is inhibited by Mycophenolic acid, ribavirin, and 6TGMP (6-thioguanine monophosphate). 6TGMP inhibition prevents purine interconversion and thus the synthesis of purine nucleotides.

Examples

Humans express the following two IMP dehydrogenase isozymes:

IMP dehydrogenase 1 Identifiers Symbol IMPDH1 Alt. symbols RP10 Entrez 3614 HUGO 6052 OMIM 146690 RefSeq NM_000883 UniProt P20839 Other data EC number 1.1.1.205 Locus Chr. 7 q31.3-q32

IMP dehydrogenase 2 Identifiers Symbol IMPDH2 Alt. symbols IMPD2 Entrez 3615 HUGO 6053 OMIM 146691 RefSeq NM_000884 UniProt P12268 Other data EC number 1.1.1.205 Locus Chr. 3 p21.2

See also

• Purine metabolism

References

1. Prosise GL, Luecke H (February 2003). "Crystal structures of Tritrichomonasfoetus inosine monophosphate dehydrogenase in complex with substrate, cofactor and analogs: a structural basis for the random-in ordered-out kinetic mechanism". J. Mol. Biol. 326 (2): 517–27. doi:10.1016/S0022-2836(02)01383-9. PMID 12559919.
2. Magasanik B, Moyed HS, Gehring LB (May 1957). "Enzymes essential for the biosynthesis of nucleic acid guanine; inosine 5'-phosphate dehydrogenase of Aerobacter aerogenes". J. Biol. Chem. 226 (1): 339–50. PMID 13428767.
3. Turner JF, King JE (April 1961). "Inosine 5'-phosphate dehydrogenase of pea seeds". Biochem. J. 79: 147–51. PMC 1205560. PMID 13778733.
4. Hedstrom L (July 2009). "IMP dehydrogenase: structure, mechanism, and inhibition". Chem. Rev. 109 (7): 2903–28. doi:10.1021/cr900021w. PMC 2737513. PMID 19480389.
5. Pimkin M, Markham GD (2009). "Inosine 5'-monophosphate dehydrogenase". Adv. Enzymol. Relat. Areas Mol. Biol. 76: 1–53. PMID 18990827.
6. Collart FR, Huberman E (October 1988). "Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs". J. Biol. Chem. 263 (30): 15769–72. PMID 2902093.
7. Natsumeda Y, Ohno S, Kawasaki H, Konno Y, Weber G, Suzuki K (March 1990). "Two distinct cDNAs for human IMP dehydrogenase". J. Biol. Chem. 265 (9): 5292–5. PMID 1969416.

Further reading

• Wang J, Yang JW, Zeevi A, Webber SA, Girnita DM, Selby R, Fu J, Shah T, Pravica V, Hutchinson IV, Burckart GJ (May 2008). "IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients". Clin. Pharmacol. Ther. 83 (5): 711–7. doi:10.1038/sj.clpt.6100347. PMID 17851563.

This article incorporates text from the public domain Pfam and InterPro IPR001093