IMPDH tetramers binds IMPDH inhibitors

Stable Identifier
R-HSA-9678749
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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IMPDH tetramers binds IMPDH inhibitors
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Inhibition of host inosine monophosphate dehydrogenases 1 and 2 (IMPDH1, IMPDH2) and subsequent depletion of cellular GTP pools is proposed to be a mechanism of action of IMPDH inhibitors (ribavirin, thioguanine, mycophenolic acid). IMPDH tetramers catalyzes the rate-limiting step where inosine 5′-monophosphate is converted to xanthine monophosphate during guanosine monophosphate (GMP) synthesis. GMP is later converted to guanosine triphosphate (GTP). IMPDH inhibitors mimic inosine 5′-monophosphate and act as competitive inhibitors of IMPDH (Nelson et al. 1990, Vethe et al. 2008, Elgemeie 2003, Te et al. 2007). Inhibited de novo synthesis of guanine nucleotides and decreased intracellular GTP pools leads to a decline in viral protein synthesis and limit replication of viral genomes (Mori et al. 2011).
Literature References
PubMed ID Title Journal Year
18609073 IMP dehydrogenase basal activity in MOLT-4 human leukaemia cells is altered by mycophenolic acid and 6-thioguanosine

Bremer, S, Bergan, S, Vethe, NT

Scand. J. Clin. Lab. Invest. 2008
1967654 Synthesis and immunosuppressive activity of some side-chain variants of mycophenolic acid

Allison, AC, Nelson, PH, Wang, CC, Eugui, E

J. Med. Chem. 1990
21320556 Mechanism of action of ribavirin in a novel hepatitis C virus replication cell system

Ariumi, Y, Dansako, H, Kato, N, Ikeda, M, Wakita, T, Mori, K

Virus Res. 2011
21960835 Mechanism of action of ribavirin in the treatment of chronic hepatitis C

Te, HS, Randall, G, Jensen, DM

Gastroenterol Hepatol (N Y) 2007
14529546 Thioguanine, mercaptopurine: their analogs and nucleosides as antimetabolites

Elgemeie, GH

Curr. Pharm. Des. 2003
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Authored
Jassal, B  (2020-03-23)
Reviewed
Shoichet, BK  (2020-05-14)
Created
Jassal, B  (2020-03-23)
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