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Literature summary for 3.4.21.91 extracted from

  • Shiryaev, S.A.; Farhy, C.; Pinto, A.; Huang, C.T.; Simonetti, N.; Elong Ngono, A.; Dewing, A.; Shresta, S.; Pinkerton, A.B.; Cieplak, P.; Strongin, A.Y.; Terskikh, A.V.
    Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists (2017), Antiviral Res., 143, 218-229 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.21.91

Inhibitors

Inhibitors Comment Organism Structure
5,6-dichloro-2H-triazolo[4,5-b]pyrazine NSC157058, the inhibitor decreases ZIKV infection in mice Zika virus
6-(4-chlorophenyl)-3-[[3-[[6-(4-chlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]methoxy]phenoxy]methyl]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole NSC716903 Zika virus
Aprotinin a 60-amino acid bovine pancreatic trypsin inhibitor and an efficient inhibitor of ZIKV NS2B-NS3pro Zika virus
additional information identification of structural scaffolds for allosteric small-molecule inhibitors of this protease, overview. Molecular modeling of the protease-inhibitor complexes suggests that these compounds bind to the druggable cavity in the NS2B-NS3 protease interface and affect productive interactions of the protease domain with its cofactor. The most potent compound demonstrate efficient inhibition of ZIKV propagation in vitro in human fetal neural progenitor cells and in vivo in SJL mice. Docking study and in silico modeling of ZIKV NS2B-NS3pro complexed with inhibitors Zika virus
N-[4-[5-(4-acetamidophenyl)pentyl]phenyl]acetamide NSC86414 Zika virus

Organism

Organism UniProt Comment Textmining
Zika virus A0A024B7W1 ZIKV
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
human neural transcription factor Sox2 + H2O the substrate protein exhibits likely cleavage sites for NS2B-NS3pro: K95RLR-A99 and R110PRRK-T115 Zika virus ?
-
 ?
additional information no activity with human maltose binding protein Zika virus ?
-
 ?
Pyr-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
-
 Zika virus Pyr-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
 ?

Synonyms

Synonyms Comment Organism
NS2B-NS3 protease
-
 Zika virus
two-component NS2B-NS3 protease
-
 Zika virus
ZIKV protease
-
 Zika virus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
20
-
 assay at Zika virus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Zika virus

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00007
-
 Aprotinin pH 8.0, 20°C Zika virus
0.00082
-
 5,6-dichloro-2H-triazolo[4,5-b]pyrazine pH 8.0, 20°C Zika virus

General Information

General Information Comment Organism
additional information structure-function studies of ZIKV NS2B-NS3 protease Zika virus
physiological function NS2B-NS3 protease consists of the NS2B cofactor and the NS3 protease domain and is essential for cleavage of the ZIKV polyprotein precursor and generation of fully functional viral proteins. Cell toxicity assays. The enzyme cleaves human Sox2 protein, which plays a critical role in neural stem cells by maintaining the activity of multiple genes involved in self-renewal and by priming the epigenetic landscape for the onset of neuronal differentiation. Sox2 is cleaved by ZIKV NS2B-NS3pro only at a very high enzyme/substrate ratio Sox2 insufficiency results in a plethora of developmental neuronal malformations in the human brain Zika virus