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Literature summary for 2.7.7.48 extracted from

  • Agudo, R.; Arias, A.; Pariente, N.; Perales, C.; Escarmis, C.; Jorge, A.; Marina, A.; Domingo, E.
    Molecular characterization of a dual inhibitory and mutagenic activity of 5-fluorouridine triphosphate on viral RNA synthesis. Implications for lethal mutagenesis (2008), J. Mol. Biol., 382, 652-666.
    View publication on PubMed
Search for more literature for 2.7.7.48

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression in Escherichia coli Foot-and-mouth disease virus

Inhibitors

Inhibitors Comment Organism Structure
5-fluorouridine triphosphate 5-fluorouridine triphosphate is a strong competitive inhibitor of VPg uridylylation by FMDV 3D in vitro, versus UTP, FUTP, dTTP, ATP, CTP, or GTP, uridylylation at VPg Tyr3, which is located near the active site of 3D, at the RNA binding cleft of 3D, binding structure from crystal structure, overview. No inhibition with oligoT primers Foot-and-mouth disease virus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Foot-and-mouth disease virus the initiation of FMDV RNA synthesis is strongly inhibited by 5-fluorouridine triphosphate, and it is also an inhibitor of FMDV RNA elongation, overview ?
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Organism

Organism UniProt Comment Textmining
Foot-and-mouth disease virus
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 i.e. FMDV
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5-fluorouridine triphosphate + RNAn the enzyme incorporates 5-fluorouridine monophosphate during RNA elongation in place of UMP or CMP using homopolymeric and heteropolymeric templates. Incorporation of 5-fluorouridine monophosphate does not prevent chain elongation, and, in some sequence contexts, it favors misincorporations at downstream positions. 5-Fluorouridine monophosphate is incorporated into the nascent RNA and occupies the new 3'-end of the primer at the active site of the enzyme. 5-Fluorouridine monophosphate establishes a Watson and Crick pair with the corresponding acceptor AMP in the template strand and an additional hydrogen bond with Ser304 of the polymerase. Further interactions, similar to those observed with standard nucleotides, contribute also to stabilize 5-fluorouridine monophosphate in the 3'-terminus of the RNA. When present in the template, 5-fluorouridine monophosphate directs the incorporation of AMP and GMP, with ATP being a more effective substrate than GTP. The misincorporation of GMP is 17fold faster opposite 5-fluorouridine than opposite U in the template. But Incorporated 5-fluorouridine monophosphate is not a chain terminator during RNA elongation Foot-and-mouth disease virus diphosphate + RNAn+1 RNA with incoporated 5-fluorouridine phosphate ?
additional information the initiation of FMDV RNA synthesis is strongly inhibited by 5-fluorouridine triphosphate, and it is also an inhibitor of FMDV RNA elongation, overview Foot-and-mouth disease virus ?
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nucleoside triphosphate + RNAn purified recombinant FMDV 3D is active in polymerization assays using homopolymeric and heteropolymeric primer templates and in binding to RNA Foot-and-mouth disease virus diphosphate + RNAn+1
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Synonyms

Synonyms Comment Organism
FMDV 3D
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 Foot-and-mouth disease virus
RDRP
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 Foot-and-mouth disease virus
RNA-dependent RNA polymerase
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 Foot-and-mouth disease virus

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
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 additional information kinetics of inhibition of VPg uridylylation, overview Foot-and-mouth disease virus