Biology:IMP dehydrogenase
| IMP dehydrogenase | |||||||||
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 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 / QuickGO | ||||||||
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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 [math]\displaystyle{ \rightleftharpoons }[/math] 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:
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See also
References
- ↑ 1.0 1.1 "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. February 2003. doi:10.1016/S0022-2836(02)01383-9. PMID 12559919.
- ↑ "Enzymes essential for the biosynthesis of nucleic acid guanine; inosine 5'-phosphate dehydrogenase of Aerobacter aerogenes". J. Biol. Chem. 226 (1): 339–50. May 1957. PMID 13428767.
- ↑ "Inosine 5'-phosphate dehydrogenase of pea seeds". Biochem. J. 79: 147–51. April 1961. PMID 13778733.
- ↑ 4.0 4.1 Hedstrom L (July 2009). "IMP dehydrogenase: structure, mechanism, and inhibition". Chem. Rev. 109 (7): 2903–28. doi:10.1021/cr900021w. PMID 19480389.
- ↑ "Inosine 5'-monophosphate dehydrogenase". Adv. Enzymol. Relat. Areas Mol. Biol. 76: 1–53. 2009. PMID 18990827.
- ↑ "Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs". J. Biol. Chem. 263 (30): 15769–72. October 1988. PMID 2902093.
- ↑ "Two distinct cDNAs for human IMP dehydrogenase". J. Biol. Chem. 265 (9): 5292–5. March 1990. PMID 1969416.
Further reading
- "IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients". Clin. Pharmacol. Ther. 83 (5): 711–7. May 2008. doi:10.1038/sj.clpt.6100347. PMID 17851563.
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