Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.7.48 extracted from

  • Deredge, D.; Li, J.; Johnson, K.A.; Wintrode, P.L.
    Hydrogen/deuterium exchange kinetics demonstrate long range allosteric effects of thumb site 2 inhibitors of hepatitis C viral RNA-dependent RNA polymerase (2016), J. Biol. Chem., 291, 10078-10088.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.7.48

Application

Application Comment Organism
drug development the enzyme is a target for inhibitor design Hepacivirus C

Inhibitors

Inhibitors Comment Organism Structure
filibuvir
-
 Hepacivirus C
GS-9669
-
 Hepacivirus C
lomibuvir
-
 Hepacivirus C
additional information non-nucleoside analogue inhibitors are being developed as part of a multidrug regiment to treat hepatitis C viral infections. Particularly promising are inhibitors that bind to the surface of the thumb domain of the viral RNA-dependent RNA polymerase. Kinetic analysis shows that non-nucleoside inhibitors binding to thumb site-2 (NNI2) do not block initiation or elongation of RNA synthesis, rather, they block the transition from the initiation to elongation, which is thought to proceed with significant structural rearrangement of the enzyme-RNA complex. Mapping of the effect of three NNI2 inhibitors on the conformational dynamics of the enzyme using hydrogen/deuterium exchange kinetics, overview. NNI2 inhibitors act through long range allosteric effects, revealing important conformational changes underlying normal polymerase function. Losses in conformational dynamics upon binding of NNI2s is correlated with inhibitor potency Hepacivirus C

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Hepacivirus C

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
nucleoside triphosphate + RNAn Hepacivirus C
-
 diphosphate + RNAn+1
-
 ?

Organism

Organism UniProt Comment Textmining
Hepacivirus C
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
nucleoside triphosphate + RNAn
-
 Hepacivirus C diphosphate + RNAn+1
-
 ?

Synonyms

Synonyms Comment Organism
NS5B
-
 Hepacivirus C
RNA-dependent RNA polymerase
-
 Hepacivirus C

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Hepacivirus C

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Hepacivirus C