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Literature summary extracted from

  • Hernandez Alvarez, L.; Naranjo Feliciano, D.; Hernandez Gonzalez, J.E.; de Oliveira Soares, R.O.; Barreto Gomes, D.E.; Pascutti, P.G.
    Insights into the Interactions of Fasciola hepatica cathepsin L3 with a substrate and potential novel inhibitors through in silico approaches (2015), PLoS Negl. Trop. Dis., 9, e0003759 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.4.22.B62 drug development cathepsin L3 is a protease that plays important roles during the life cycle of fluke. Due to its particular collagenolytic activity it is considered an attractive drug target in the infective phase of Fasciola hepatica Fasciola hepatica

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.22.15 (2E)-N'-(2-[(naphthalen-1-ylmethyl)sulfanyl]acetyl)-3-phenylprop-2-enehydrazide
-
 Fasciola hepatica
3.4.22.15 1-N-[3,5-bis (trifluoromethyl) phenyl]-2-N-(1-ethynylcyclohexyl) benzene-1,2-dicarboxamide
-
 Fasciola hepatica
3.4.22.15 2-([4-benzyl-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl)-1-(1,2,3,4-tetrahydroquinolin-1-yl)ethan-1-one
-
 Fasciola hepatica
3.4.22.15 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(5-methyl-3-phenyl-1,2-oxazole-4-carbonyl)benzohydrazide
-
 Fasciola hepatica
3.4.22.15 4-[4-(benzyloxy)phenyl]-3-([(4-methylphenyl)methyl]sulfanyl)-4,5-dihydro-1H-1,2,4-triazol-5-one
-
 Fasciola hepatica
3.4.22.15 additional information structure-based design of enzyme inhibitors through a computational study that combined virtual screening, molecular dynamics simulations, and binding free energy calculations. Docking protocol validation is carried out through the non-covalent re-docking of nitrile ((2S,4R)-1-[1-(4-chlorophenyl) cyclopropyl] carbonyl-4-(2-chlorophenyl) sulfonyl-N-[1-(iminomethyl)cyclopropyl] pyrrolidine-2-carboxamide) inhibitor into the active site of this protease, three-dimensional structure determination using the crystal structure of proFhCL1 C25G (PDB ID 2O6X) as a template Fasciola hepatica
3.4.22.B62 (2E)-N'-(2-[(naphthalen-1-ylmethyl)sulfanyl]acetyl)-3-phenylprop-2-enehydrazide
-
 Fasciola hepatica
3.4.22.B62 2-([4-benzyl-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl)-1-(1,2,3,4-tetrahydroquinolin-1-yl)ethan-1-one
-
 Fasciola hepatica
3.4.22.B62 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(5-methyl-3-phenyl-1,2-oxazole-4-carbonyl)benzohydrazide
-
 Fasciola hepatica
3.4.22.B62 4-[4-(benzyloxy)phenyl]-3-([(4-methylphenyl)methyl]sulfanyl)-4,5-dihydro-1H-1,2,4-triazol-5-one
-
 Fasciola hepatica
3.4.22.B62 additional information virtual inhibitor screening is carried out by docking inhibitors obtained from the MYBRIDGE-HitFinder database to FhCL3 and human cathepsin L substrate-binding sites. On the basis of dock-scores, five compounds are predicted as selective inhibitors of FhCL3, molecular dynamic simulations. The active site-binding compounds prevent substrate processing by competitive inhibition. Structure-based drug design strategy, overview. Calculation of inhibition kinetics and thermodynamics Fasciola hepatica
3.4.22.B62 N1-[3,5-bis(trifluoromethyl)phenyl]-N2-(1-ethynylcyclohexyl)benzene-1,2-dicarboxamide
-
 Fasciola hepatica

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
3.4.22.B62 extracellular the enzyme is secreted Fasciola hepatica
-
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.4.22.B62 Collagen + H2O Fasciola hepatica
-
 ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.4.22.15 Fasciola hepatica B3TM67
-
-
3.4.22.B62 Fasciola hepatica Q9GRW6
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.22.15 acetyl-AGPRNAA-N-methyl amide + H2O docking study Fasciola hepatica acetyl-AGPR + NAA-N-methyl amide
-
 ?
3.4.22.15 additional information analysis of substrate specificity of FhCL3, strong preference of the cathepsin for Pro and Gly residues at P2 and P3 sites, respectively, of substrates. Residues residues, Q19, G23, G25, W26, G67, W69, Y143, T161, H162 and W184, of FhCL3 largely contribute to the substrate binding. W69, Y143 and T161 have the largest per-residue free energy contributions to the complex formation, interaction analysis, overview Fasciola hepatica ?
-
 ?
3.4.22.B62 Collagen + H2O
-
 Fasciola hepatica ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.4.22.15 cathepsin L3
-
 Fasciola hepatica
3.4.22.15 CL3
-
 Fasciola hepatica
3.4.22.15 FhCL3
-
 Fasciola hepatica
3.4.22.B62 FhCL3
-
 Fasciola hepatica

General Information

EC Number General Information Comment Organism
3.4.22.15 physiological function the mature enzyme is mainly involved in penetration and immune response evasion of the host Fasciola hepatica
3.4.22.B62 additional information homology modeling of FhCL3 using the three dimensional structure of proFhCL1 C25G, PDB ID 2O6X, as a template Fasciola hepatica