IMP dehydrogenase EC 220.127.116.11 (Inosine-5'-monophosphate dehydrogenase) (Inosinic acid dehydrogenaseis) (IMPDH) an enzyme that converts inosine monophosphate to xanthosine monophosphate:
- inosine 5'-phosphate + NAD+ + H2O xanthosine 5'-phosphate + NADH + H+
It catalyzes the rate-limiting reaction of de novo GTP biosynthesis.
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. 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.
It is inhibited by Mycophenolic acid, ribavirin, and 6TGMP (6-thioguanine monophosphate). 6TGMP inhibition prevents purine interconversion and thus the synthesis of purine nucleotides.
Humans express the following two IMP dehydrogenase isozymes:
- 1 2 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.
- ↑ 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.
- ↑ Turner JF, King JE (April 1961). "Inosine 5'-phosphate dehydrogenase of pea seeds". Biochem. J. 79: 147–51. PMC 1205560. PMID 13778733.
- 1 2 Hedstrom L (July 2009). "IMP dehydrogenase: structure, mechanism, and inhibition". Chem. Rev. 109 (7): 2903–28. doi:10.1021/cr900021w. PMC 2737513. PMID 19480389.
- ↑ Pimkin M, Markham GD (2009). "Inosine 5'-monophosphate dehydrogenase". Adv. Enzymol. Relat. Areas Mol. Biol. 76: 1–53. PMID 18990827.
- ↑ 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.
- ↑ 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.
- 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