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Literature summary extracted from

  • Sun, J.; Dahan, A.; Walls, Z.F.; Lai, L.; Lee, K.D.; Amidon, G.L.
    Specificity of a prodrug-activating enzyme hVACVase: the leaving group effect (2010), Mol. Pharm., 7, 2362-2368.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.1.1.43 drug development in hVACVase-catalyzed reactions, the leaving group of the substrate corresponds to the drug moiety of the prodrug, making the leaving group effect essential for the rational design of prodrugs targeting hVACVase activation Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.1.1.43 recombinant expression of the His6-tagged hVACVase construct, M-S tag-PDLGTLVPRGSMGM-hVACVase-AAALE-His tag, in Escherichia coli Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.1.1.43 additional information
-
 additional information Michaelis-Menten kinetics Homo sapiens
3.1.1.43 0.014
-
 valine 4-nitrobenzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 0.046
-
 valine [3-(hydroxymethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 0.06
-
 valine benzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 0.068
-
 valacyclovir pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 0.099
-
 phenylalanine benzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 0.207
-
 phenylalanine [3-(hydroxymethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 1.81
-
 valine [3-(aminomethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 5.14
-
 phenylalanine methyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 6.7
-
 phenylalanine ethyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
3.1.1.43 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.1.1.43 recombinant His6-tagged hVACVase construct from Escherichia coli by affinity chromatography Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
3.1.1.43 an alpha-amino acid ester + H2O = an alpha-amino acid + an alcohol hVACVase is a serine hydrolase with a catalytic triad S122-H255-D227 Homo sapiens
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.1.1.43 epithelial cell
-
 Homo sapiens
-
3.1.1.43 intestine
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.1.43 5'-O-L-valyl-2'-deoxy-5-fluorouridine + H2O
-
 Homo sapiens L-valine + 2'-deoxy-5-fluorouridine
-
 ?
3.1.1.43 additional information hVACVase is a prodrug-activating enzyme for amino acid prodrugs including the antiviral drugs valacyclovir and valganciclovir. In hVACVase-catalyzed reactions, the leaving group of the substrate corresponds to the drug moiety of the prodrug, the substrate leaving group affects both, binding and specific activity of hVACVase-catalyzed activation, overview. Effect of the leaving group of a series of valine esters, phenylalanine esters, and a valine amide on the efficiency of hVACVase-mediated prodrug activation. Except for phenylalanine methyl and ethyl esters, all of the ester substrates exhibit a relatively high specificity constant. The valine amide Val-[3-(aminomethyl)phenyl]guanidine exhibits significantly higher Km and lower kcat values compared to the corresponding ester Val-[3-(hydroxymethyl)phenyl]guanidine, indicating poor specificity for hVACVase, overview. While the phenylalanine benzyl and ethyl esters are hVACVase substrates, phenylalanine t-butyl ester is not a substrate Homo sapiens ?
-
 ?
3.1.1.43 phenylalanine benzyl ester + H2O
-
 Homo sapiens L-phenylalanine + benzyl alcohol
-
 ?
3.1.1.43 phenylalanine ethyl ester + H2O
-
 Homo sapiens L-phenylalanine + ethanol
-
 ?
3.1.1.43 phenylalanine methyl ester + H2O
-
 Homo sapiens L-phenylalanine + methanol
-
 ?
3.1.1.43 phenylalanine [3-(hydroxymethyl)phenyl]guanidine + H2O
-
 Homo sapiens L-phenylalanine + [3-(hydroxymethyl)phenyl]guanidine
-
 ?
3.1.1.43 valacyclovir + H2O
-
 Homo sapiens L-valine + 2-amino-9-[(2-hydroxyethyloxy)methyl]-1,9-dihydro-6H-purin-6-one
-
 ?
3.1.1.43 valganciclovir + H2O
-
 Homo sapiens L-valine + 2-amino-9-[[(1,3-dihydroxpropan-2-yl)oxy]methyl]-1,9-dihydro-6H-purin-6-one
-
 ?
3.1.1.43 valine 4-nitrobenzyl ester + H2O
-
 Homo sapiens L-valine + 4-nitrobenzyl alcohol
-
 ?
3.1.1.43 valine benzyl ester + H2O
-
 Homo sapiens L-valine + benzyl alcohol
-
 ?
3.1.1.43 valine [3-(aminomethyl)phenyl]guanidine + H2O
-
 Homo sapiens L-valine + [3-(aminomethyl)phenyl]guanidine
-
 ?
3.1.1.43 valine [3-(hydroxymethyl)phenyl]guanidine + H2O
-
 Homo sapiens L-valine + [3-(hydroxymethyl)phenyl]guanidine
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.1.1.43 VACVase
-
 Homo sapiens
3.1.1.43 valacyclovirase
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.1.1.43 37
-
 assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.1.1.43 0.0023
-
 valine [3-(aminomethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 58
-
 valacyclovir pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 60
-
 valine benzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 93
-
 phenylalanine ethyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 130
-
 valine 4-nitrobenzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 154
-
 valine [3-(hydroxymethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 228
-
 phenylalanine methyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 345
-
 phenylalanine [3-(hydroxymethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 395
-
 phenylalanine benzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.1.1.43 7.4
-
 assay at Homo sapiens

General Information

EC Number General Information Comment Organism
3.1.1.43 physiological function hVACVase is a prodrug-activating enzyme for amino acid prodrugs including the antiviral drugs valacyclovir and valganciclovir Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
3.1.1.43 0.0013
-
 valine [3-(aminomethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 14
-
 phenylalanine ethyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 44
-
 phenylalanine methyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 850
-
 valacyclovir pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 992
-
 valine benzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 1660
-
 phenylalanine [3-(hydroxymethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 3370
-
 valine [3-(hydroxymethyl)phenyl]guanidine pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 3980
-
 phenylalanine benzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens
3.1.1.43 9490
-
 valine 4-nitrobenzyl ester pH 7.4, 37°C, recombinant enzyme Homo sapiens