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Literature summary for 3.4.22.66 extracted from

  • Galasiti Kankanamalage, A.C.; Weerawarna, P.M.; Rathnayake, A.D.; Kim, Y.; Mehzabeen, N.; Battaile, K.P.; Lovell, S.; Chang, K.O.; Groutas, W.C.
    Putative structural rearrangements associated with the interaction of macrocyclic inhibitors with norovirus 3CL protease (2019), Proteins, 87, 579-587 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.22.66

Crystallization (Commentary)

Crystallization (Comment) Organism
sitting drop vapor diffusion plates at 20°C, 2.25 A resolution structure of Norovirus 3CL protease in complex with a triazole-based macrocyclic inhibitor Norwalk virus

Inhibitors

Inhibitors Comment Organism Structure
benzyl ((3S,6S,9S,Z)-6-(cyclohexylmethyl)-9-formyl-4,7,12-trioxo-11H-5,8,13-triaza-1(4,1)-triazolacyclohexadecaphane-3-yl)carbamate
-
 Norwalk virus
benzyl ((3S,6S,9S,Z)-9-formyl-6-isobutyl-4,7,12-trioxo-11H-5,8,13-triaza-1(4,1)-triazolacyclohexadecaphane-3-yl)carbamate
-
 Norwalk virus
benzyl ((8S,11S,14S,Z)-11-(cyclohexylmethyl)-8-formyl-5,10,13-trioxo-11H-4,9,12-triaza-1(1,4)-triazolacyclopentadecaphane-14-yl)carbamate
-
 Norwalk virus

Organism

Organism UniProt Comment Textmining
Norwalk virus Q83883
-
-
Norwalk virus GI Q83883
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Edans-DFHLQGP-Dabcyl + H2O
-
 Norwalk virus Edans-DFHLQ + GP-Dabcyl
-
 ?
Edans-DFHLQGP-Dabcyl + H2O
-
 Norwalk virus GI Edans-DFHLQ + GP-Dabcyl
-
 ?

Synonyms

Synonyms Comment Organism
3C-like cysteine protease
-
 Norwalk virus
NV 3CLpro
-
 Norwalk virus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0016
-
 pH 8.0, 37°C Norwalk virus benzyl ((3S,6S,9S,Z)-6-(cyclohexylmethyl)-9-formyl-4,7,12-trioxo-11H-5,8,13-triaza-1(4,1)-triazolacyclohexadecaphane-3-yl)carbamate
0.0024
-
 pH 8.0, 37°C Norwalk virus benzyl ((3S,6S,9S,Z)-9-formyl-6-isobutyl-4,7,12-trioxo-11H-5,8,13-triaza-1(4,1)-triazolacyclohexadecaphane-3-yl)carbamate
0.0029
-
 pH 8.0, 37°C Norwalk virus benzyl ((8S,11S,14S,Z)-11-(cyclohexylmethyl)-8-formyl-5,10,13-trioxo-11H-4,9,12-triaza-1(1,4)-triazolacyclopentadecaphane-14-yl)carbamate

General Information

General Information Comment Organism
drug target the enzyme is an attractive target for the discovery of norovirus therapeutics and prophylactics. In order to gain insight and understanding into the interaction of macrocyclic inhibitors with the enzyme, as well as probe the effect of ring size on pharmacological activity and cellular permeability, additional macrocyclic inhibitors are synthesized and high resolution cocrystal structures determined. The macrocyclic scaffold may hamper optimal binding to the active site by impeding concerted cross-talk between the S2 and S4 subsites Norwalk virus
physiological function noroviruses have a single-stranded, positive sense 7 to 8 kb RNA genome which encodes a polyprotein precursor that is processed by a virus-encoded 3C-like cysteine protease (NV 3CLpro) to generate at least six mature nonstructural proteins. Processing of the polyprotein is essential for virus replication Norwalk virus