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Literature summary for 3.4.22.15 extracted from

  • Ferraro, F.; Merlino, A.; Dell Oca, N.; Gil, J.; Tort, J.F.; Gonzalez, M.; Cerecetto, H.; Cabrera, M.; Corvo, I.
    Identification of chalcones as Fasciola hepatica cathepsin L inhibitors using a comprehensive experimental and computational approach (2016), PLoS Negl. Trop. Dis., 10, e0004834 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.22.15

Application

Application Comment Organism
drug development cathepsins, including cathepsin L, are interesting targets for drug development in an effort to avoid parasite infection or reduce parasite burden and the pathogenic effects of the infection Fasciola hepatica

Cloned(Commentary)

Cloned (Comment) Organism
gene CL1, recombinant enzyme expression in Hansenula polymorpha Fasciola hepatica
gene CL3, recombinant enzyme expression in Hansenula polymorpha Fasciola hepatica

Inhibitors

Inhibitors Comment Organism Structure
(2E)-1,3-diphenylprop-2-en-1-one 33% inhibition of FhCL1; 4% inhibition of FhCL3 Fasciola hepatica
(2E)-1-(2-hydroxyphenyl)-3-(3-nitrophenyl)prop-2-en-1-one 26% inhibition of FhCL1; 37% inhibition of FhCL3 Fasciola hepatica
(2E)-1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one 3% inhibition of FhCL3; 48% inhibition of FhCL1 Fasciola hepatica
(2E)-1-(2-hydroxyphenyl)-3-(4-phenoxyphenyl)prop-2-en-1-one 16% inhibition of FhCL3; 8% inhibition of FhCL1 Fasciola hepatica
(2E)-1-(2-hydroxyphenyl)-3-(pyridin-2-yl)prop-2-en-1-one 20% inhibition of FhCL19; 54% inhibition of FhCL1 Fasciola hepatica
(2E)-1-(2-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one 52% inhibition of FhCL1; 9% inhibition of FhCL3 Fasciola hepatica
(2E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one 16% inhibition of FhCL2 Fasciola hepatica
(2E)-1-(2-hydroxyphenyl)-3-[4-(methylsulfanyl)phenyl]prop-2-en-1-one 19% inhibition of FhCL3 Fasciola hepatica
(2E)-1-(7-hydroxynaphthalen-1-yl)-3-(naphthalen-1-yl)prop-2-en-1-one a slow-reversible inhibitor that interacts with the Cys-His catalytic dyad and key S2 and S3 pocket residues, causing 65% inhibition of FhCL3, enzyme binding structure by molecular docking, overview. Analysis of fasciolicide activity of C34 on vitro cultu; a slow-reversible inhibitor that interacts with the Cys-His catalytic dyad and key S2 and S3 pocket residues, causing 75% inhibition of FhCL1, enzyme binding structure by molecular docking, overview. Analysis of fasciolicide activity of C34 on vitro cultu Fasciola hepatica
(2E)-1-(7-hydroxynaphthalen-1-yl)-3-(naphthalen-2-yl)prop-2-en-1-one 44% inhibition of FhCL3; 67% inhibition of FhCL1 Fasciola hepatica
(2E)-1-(8-hydroxynaphthalen-2-yl)-3-(naphthalen-2-yl)prop-2-en-1-one 29% inhibition of FhCL3; 65% inhibition of FhCL1 Fasciola hepatica
(2E)-1-(naphthalen-2-yl)-3-phenylprop-2-en-1-one 13% inhibition of FhCL3; 65% inhibition of FhCL1 Fasciola hepatica
(2E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1-one 4% inhibition of FhCL3; 8% inhibition of FhCL1 Fasciola hepatica
(2E)-3-(1,3-benzodioxol-5-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one 11% inhibition of FhCL1; 19% inhibition of FhCL3 Fasciola hepatica
(2E)-3-(2-bromophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one 29% inhibition of FhCL1; 33% inhibition of FhCL3 Fasciola hepatica
(2E)-3-(3,4-dimethoxyphenyl)-1-phenylprop-2-en-1-one 2% inhibition of FhCL3; 35% inhibition of FhCL1 Fasciola hepatica
(2E)-3-(4-aminophenyl)-1-phenylprop-2-en-1-one 2% inhibition of FhCL3; 4% inhibition of FhCL1 Fasciola hepatica
(2E)-3-(4-bromophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one 12% inhibition of FhCL3; 19% inhibition of FhCL1 Fasciola hepatica
(2E)-3-(4-bromophenyl)-1-phenylprop-2-en-1-one 12% inhibition of FhCL3; 52% inhibition of FhCL1 Fasciola hepatica
(2E)-3-(4-chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one 23% inhibition of FhCL3; 63% inhibition of FhCL1 Fasciola hepatica
(2E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one 25% inhibition of FhCL1; 6% inhibition of FhCL43 Fasciola hepatica
(2E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one 48% inhibition of FhCL1; 4% inhibition of FhCL3 Fasciola hepatica
(2E)-3-(furan-2-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one 4% inhibition of FhCL3; 57% inhibition of FhCL1 Fasciola hepatica
(2E)-3-(naphthalen-1-yl)-1-phenylprop-2-en-1-one 17% inhibition of FhCL1; 27% inhibition of FhCL3 Fasciola hepatica
(2E)-3-[4-(dimethylamino)phenyl]-1-(2-hydroxyphenyl)prop-2-en-1-one 20% inhibition of FhCL3; 34% inhibition of FhCL1 Fasciola hepatica
(2E)-3-[4-(methylsulfanyl)phenyl]-1-phenylprop-2-en-1-one 26% inhibition of FhCL3; 8% inhibition of FhCL1 Fasciola hepatica
1-hydroxy-6-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]-2,1,3-benzoxadiazol-1-ium 21% inhibition of FhCL1; 26% inhibition of FhCL3 Fasciola hepatica
1-[(1E)-3-phenylprop-1-en-1-yl]naphthalene 38% inhibition of FhCL1; 39% inhibition of FhCL3 Fasciola hepatica
2-(4-bromophenyl)-4H-chromen-4-one 19% inhibition of FhCL3; 21% inhibition of FhCL1 Fasciola hepatica
2-(4-chlorophenyl)-4H-chromen-4-one 17% inhibition of FhCL3 Fasciola hepatica
2-hydroxy-4-[(1E)-3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl]-1,2,5-oxadiazol-2-ium 14% inhibition of FhCL3; 48% inhibition of FhCL1 Fasciola hepatica
2-phenyl-4H-chromen-4-one 5% inhibition of FhCL1; 8% inhibition of FhCL3 Fasciola hepatica
2-[(1E)-3-phenylprop-1-en-1-yl]naphthalene 38% inhibition of FhCL3; 62% inhibition of FhCL1 Fasciola hepatica
2-[(2E)-3-(naphthalen-1-yl)prop-2-en-1-yl]phenol 32% inhibition of FhCL3; 42% inhibition of FhCL1 Fasciola hepatica
2-[(2E)-3-(naphthalen-2-yl)prop-2-en-1-yl]phenol 41% inhibition of FhCL3; 61% inhibition of FhCL1 Fasciola hepatica
E-64c
-
 Fasciola hepatica
additional information identification of chalcones as Fasciola hepatica cathepsin L inhibitors using a comprehensive experimental and computational approach, library screening, overview. No inhibition of cathepsin L1 by (2E)-1-(2-hydroxyphenyl)-3-[4-(methylsulfanyl)phenyl]prop-2-en-1-one, N-[4-[(1E)-3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl]phenyl]acetamide, and 2-(4-chlorophenyl)-4H-chromen-4-one; identification of chalcones as Fasciola hepatica cathepsin L inhibitors using a comprehensive experimental and computational approach, library screening, overview. No inhibition of cathepsin L3 by (2E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one, (2E)-1-(2-hydroxyphenyl)-3-(pyridin-2-yl)prop-2-en-1-one, and (2Z)-1-(2-hydroxyphenyl)-3-(pyridin-2-yl)prop-2-en-1-one; not inhibitory: (2E)-1-(2-hydroxyphenyl)-3-[4-(methylsulfanyl)phenyl]prop-2-en-1-one; not inhibitory: N-[4-[(1E)-3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl]phenyl]acetamide Fasciola hepatica
N-[4-[(1E)-3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl]phenyl]acetamide 32% inhibition of FhCL3; 6% inhibition of FhCL1 Fasciola hepatica
N-[4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]phenyl]acetamide 12% inhibition of FhCL3; 14% inhibition of FhCL1 Fasciola hepatica
N-[4-[(1Z)-3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl]phenyl]acetamide 13% inhibition of FhCL3 Fasciola hepatica
quercetin 15% inhibition of FhCL1; 8% inhibition of FhCL3 Fasciola hepatica

Localization

Localization Comment Organism GeneOntology No. Textmining
extracellular the enzyme is secreted Fasciola hepatica
-
-

Organism

Organism UniProt Comment Textmining
Fasciola hepatica B3TM67
-
-
Fasciola hepatica Q7JNQ9
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification the proenzyme is autocatalytically activated to the mature form Fasciola hepatica

Purification (Commentary)

Purification (Comment) Organism
recombinant extracellular enzyme partially from Hansenula polymorpha by ultrafiltration and dialysis Fasciola hepatica

Source Tissue

Source Tissue Comment Organism Textmining
adult FhCL1 is the main cathepsin expressed by adult flukes Fasciola hepatica
-
juvenile newly excysted juveniles (NEJ), FhCL3 is the only cathepsin L found in the early NEJ excretion/secretion products Fasciola hepatica
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
benzyloxycarbonyl-L-Val-L-Leu-L-Lys-7-amido-4-methylcoumarin + H2O
-
 Fasciola hepatica benzyloxycarbonyl-L-Val-L-Leu-L-Lys + 7-amino-4-methylcoumarin
-
 ?
additional information the enzyme performs autocleavage of its proform Fasciola hepatica ?
-
 ?
tosyl-Gly-L-Pro-L-Arg-7-amido-4-methylcoumarin + H2O
-
 Fasciola hepatica tosyl-Gly-L-Pro-L-Arg + 7-amino-4-methylcoumarin
-
 ?

Synonyms

Synonyms Comment Organism
cathepsin L1
-
 Fasciola hepatica
cathepsin L3
-
 Fasciola hepatica
CL1
-
 Fasciola hepatica
CL3
-
 Fasciola hepatica
FhCL1
-
 Fasciola hepatica
FhCL3
-
 Fasciola hepatica

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Fasciola hepatica

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
5
-
 autocleavage assay at Fasciola hepatica
6
-
 proteolytic assay at Fasciola hepatica

General Information

General Information Comment Organism
additional information enzyme structure analysis by molecular dynamic simulations and molecular docking, homology modelling Fasciola hepatica
additional information enzyme structure analysis by molecular dynamic simulations and molecular docking, homoloy modelling Fasciola hepatica
physiological function liver flukes secrete high amounts of cysteine proteases being key players in host-parasite interaction at all stages of their life cycle. Cathepsin L3 is expressed by the newly excysted juveniles (NEJ) and consequently take part in the first steps of mammalian host infection Fasciola hepatica