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Literature summary for 3.1.1.43 extracted from
- Specificity of a prodrug-activating enzyme hVACVase: the leaving group effect (2010), Mol. Pharm., 7, 2362-2368.
Application
| Application | Comment | Organism |
|---|---|---|
| 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)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of the His6-tagged hVACVase construct, M-S tag-PDLGTLVPRGSMGM-hVACVase-AAALE-His tag, in Escherichia coli | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten kinetics | Homo sapiens | |
| 0.014 | - |
valine 4-nitrobenzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens |  |
| 0.046 | - |
valine [3-(hydroxymethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 0.06 | - |
valine benzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 0.068 | - |
valacyclovir | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 0.099 | - |
phenylalanine benzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 0.207 | - |
phenylalanine [3-(hydroxymethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 1.81 | - |
valine [3-(aminomethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 5.14 | - |
phenylalanine methyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 6.7 | - |
phenylalanine ethyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His6-tagged hVACVase construct from Escherichia coli by affinity chromatography | Homo sapiens |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| 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 |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| epithelial cell | - |
Homo sapiens | - |
| intestine | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5'-O-L-valyl-2'-deoxy-5-fluorouridine + H2O | - |
Homo sapiens | L-valine + 2'-deoxy-5-fluorouridine | - |
? | |
| 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 | ? | - |
? | |
| phenylalanine benzyl ester + H2O | - |
Homo sapiens | L-phenylalanine + benzyl alcohol | - |
? | |
| phenylalanine ethyl ester + H2O | - |
Homo sapiens | L-phenylalanine + ethanol | - |
? | |
| phenylalanine methyl ester + H2O | - |
Homo sapiens | L-phenylalanine + methanol | - |
? | |
| phenylalanine [3-(hydroxymethyl)phenyl]guanidine + H2O | - |
Homo sapiens | L-phenylalanine + [3-(hydroxymethyl)phenyl]guanidine | - |
? | |
| valacyclovir + H2O | - |
Homo sapiens | L-valine + 2-amino-9-[(2-hydroxyethyloxy)methyl]-1,9-dihydro-6H-purin-6-one | - |
? | |
| valganciclovir + H2O | - |
Homo sapiens | L-valine + 2-amino-9-[[(1,3-dihydroxpropan-2-yl)oxy]methyl]-1,9-dihydro-6H-purin-6-one | - |
? | |
| valine 4-nitrobenzyl ester + H2O | - |
Homo sapiens | L-valine + 4-nitrobenzyl alcohol | - |
? | |
| valine benzyl ester + H2O | - |
Homo sapiens | L-valine + benzyl alcohol | - |
? | |
| valine [3-(aminomethyl)phenyl]guanidine + H2O | - |
Homo sapiens | L-valine + [3-(aminomethyl)phenyl]guanidine | - |
? | |
| valine [3-(hydroxymethyl)phenyl]guanidine + H2O | - |
Homo sapiens | L-valine + [3-(hydroxymethyl)phenyl]guanidine | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| VACVase | - |
Homo sapiens |
| valacyclovirase | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0023 | - |
valine [3-(aminomethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 58 | - |
valacyclovir | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 60 | - |
valine benzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 93 | - |
phenylalanine ethyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 130 | - |
valine 4-nitrobenzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 154 | - |
valine [3-(hydroxymethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 228 | - |
phenylalanine methyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 345 | - |
phenylalanine [3-(hydroxymethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 395 | - |
phenylalanine benzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.4 | - |
assay at | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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]
| kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0013 | - |
valine [3-(aminomethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 14 | - |
phenylalanine ethyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 44 | - |
phenylalanine methyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 850 | - |
valacyclovir | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 992 | - |
valine benzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 1660 | - |
phenylalanine [3-(hydroxymethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 3370 | - |
valine [3-(hydroxymethyl)phenyl]guanidine | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 3980 | - |
phenylalanine benzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
| 9490 | - |
valine 4-nitrobenzyl ester | pH 7.4, 37°C, recombinant enzyme | Homo sapiens | |
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