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Literature summary for 3.4.22.B80 extracted from

  • Lin, M.H.; Moses, D.C.; Hsieh, C.H.; Cheng, S.C.; Chen, Y.H.; Sun, C.Y.; Chou, C.Y.
    Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes (2018), Antiviral Res., 150, 155-163 .
    View publication on PubMed
Search for more literature for 3.4.22.B80

Application

Application Comment Organism
drug development synergistic inhibition of the enzyme by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs Middle East respiratory syndrome-related coronavirus

Crystallization (Commentary)

Crystallization (Comment) Organism
crystals of SARS-CoV PLpro in complex with 2-mercaptoethanol or glycerol are obtained at 22°C by the sitting-drop vapor-diffusion method Severe acute respiratory syndrome-related coronavirus

Inhibitors

Inhibitors Comment Organism Structure
Disulfiram allosteric inhibition. Synergistic inhibition of the enzyme by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs Middle East respiratory syndrome-related coronavirus
Disulfiram slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicates covalent inactivation. Disulfiram may act at the active site of the enzyme, forming a covalent adduct with residue Cys112. Competitive (or mixed) inhibitor Severe acute respiratory syndrome-related coronavirus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0195
-
 Dabcyl-FRLKGGAPIKGV-Edans pH 6.5, 30°C, wild-type enzyme Severe acute respiratory syndrome-related coronavirus
0.0246
-
 Dabcyl-FRLKGGAPIKGV-Edans pH 6.5, 30°C, mutant enzyme C271A Severe acute respiratory syndrome-related coronavirus
0.0288
-
 Dabcyl-FRLKGGAPIKGV-Edans pH 6.5, 30°C, wild-type enzyme Middle East respiratory syndrome-related coronavirus

Organism

Organism UniProt Comment Textmining
Middle East respiratory syndrome-related coronavirus
-
 MERS-CoV
-
Severe acute respiratory syndrome-related coronavirus P0C6X7 replicase polyprotein 1ab; human, i.e. SARS-CoV
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Dabcyl-FRLKGGAPIKGV-Edans + H2O
-
 Severe acute respiratory syndrome-related coronavirus ?
-
 ?
Dabcyl-FRLKGGAPIKGV-Edans + H2O
-
 Middle East respiratory syndrome-related coronavirus ?
-
 ?

Synonyms

Synonyms Comment Organism
MERS coronavirus papain-like protease
-
 Middle East respiratory syndrome-related coronavirus
SARS coronavirus papain-like protease
-
 Severe acute respiratory syndrome-related coronavirus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
 assay at Severe acute respiratory syndrome-related coronavirus
30
-
 assay at Middle East respiratory syndrome-related coronavirus

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.01
-
 Dabcyl-FRLKGGAPIKGV-Edans pH 6.5, 30°C, wild-type enzyme Middle East respiratory syndrome-related coronavirus
0.12
-
 Dabcyl-FRLKGGAPIKGV-Edans pH 6.5, 30°C, mutant enzyme C271A Severe acute respiratory syndrome-related coronavirus
0.18
-
 Dabcyl-FRLKGGAPIKGV-Edans pH 6.5, 30°C, wild-type enzyme Severe acute respiratory syndrome-related coronavirus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.5
-
 assay at Severe acute respiratory syndrome-related coronavirus
6.5
-
 assay at Middle East respiratory syndrome-related coronavirus

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.004
-
 Disulfiram pH 6.5, 30°C, wild-type enzyme, determined in accordance with competitive inhibition Severe acute respiratory syndrome-related coronavirus
0.0201
-
 Disulfiram pH 6.5, 30°C Middle East respiratory syndrome-related coronavirus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0044
-
 pH 6.5, 30°C, with 0.015 mM 6-thioguanine and 0.15 mycophenolic acid, wild-type enzyme Middle East respiratory syndrome-related coronavirus Disulfiram
0.0142
-
 pH 6.5, 30°C, wild-type enzyme Severe acute respiratory syndrome-related coronavirus Disulfiram
0.0181
-
 pH 6.5, 30°C, with 0.004 mM N-ethylmaleimide, wild-type enzyme Severe acute respiratory syndrome-related coronavirus Disulfiram
0.0218
-
 pH 6.5, 30°C, with 0.015 mM 6-thioguanine, wild-type enzyme Severe acute respiratory syndrome-related coronavirus Disulfiram
0.0627
-
 pH 6.5, 30°C, mutant enzyme C271A Severe acute respiratory syndrome-related coronavirus Disulfiram
0.137
-
 pH 6.5, 30°C, with 0.01 mM 6-thioguanine and 0.1 mycophenolic acid, wild-type enzyme Middle East respiratory syndrome-related coronavirus Disulfiram
0.145
-
 pH 6.5, 30°C, with 0.015 mM 6-thioguanine, wild-type enzyme Middle East respiratory syndrome-related coronavirus Disulfiram
0.217
-
 pH 6.5, 30°C, with 0.15 mycophenolic acid, wild-type enzyme Middle East respiratory syndrome-related coronavirus Disulfiram
0.227
-
 pH 6.5, 30°C, wild-type enzyme Middle East respiratory syndrome-related coronavirus Disulfiram