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Literature summary for 3.1.1.25 extracted from
- The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases (2006), J. Biol. Chem., 281, 7649-7656.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| wild-type-like rePON1-G2E6 and its various mutants are expressed as fusion proteins with thioredoxin and His6 tags | Homo sapiens |
| wild-type-like rePON1-G2E6 and its various mutants are expressed as fusion proteins with thioredoxin and His6 tags | Oryctolagus cuniculus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| H115A | activity with 5-(thioethyl)butyrolactone is 1.1% of wild-type activity, activity with 5-(thiobutyl)butyrolactone is 4.2% of wild-type activity, activity with delta-valerolactone, gamma-nonalactone or gamma-undecanoic lactone is less than 1% of wild-type activity | Oryctolagus cuniculus |
| H115A | activity with dicoumarin is 366% compared to wild-type activity, activity with delta-valerolactone is 3% of wild-type activity, activity with gamma-nonalactone is 1% of wild-type activity | Homo sapiens |
| H115Q | activity with dicoumarin is 268% compared to wild-type activity, activity with delta-valerolactone is 4.96% of wild-type activity, activity with gamma-nonalactone is 1.2% of wild-type activity. kcat/Km for delta-valerolactone is 2.2% of wild-type value, kcat/Km for gamma-nonalactone is 0.3% of wild-type value, kcat/Km for gamma-caprolactone is 1.4% of wild-type value, kcat/Km for 5-(thiobutyl)butyrolactone is 1.1% of wild-type value. Mutant with reduced lactonase activity, exhibits reduced or no biological function in ex vivo assay | Homo sapiens |
| H115Q/H134Q | activity with 5-(thioethyl)butyrolactone is 0.2% compared to wild-type activity, activity with 5-(thiobutyl)butyrolactone is 0.6% of wild-type activity, activity with delta-valerolactone, gamma-nonalactone or gamma-undecanoic lactone is less than 1% of wild-type activity | Oryctolagus cuniculus |
| H115Q/H134Q | kcat/Km for 5-(thiobutyl)butyrolactone is 0.2% of wild-type value mutant with reduced lactonase activity, exhibits reduced or no biological function in ex vivo assay | Homo sapiens |
| H115W | activity with dicoumarin is 261% compared to wild-type activity, activity with delta-valerolactone is 0.6% of wild-type activity, activity with gamma-nonalactone is 0.1% of wild-type activity | Homo sapiens |
| H134Q | activity with dicoumarin is 77% compared to wild-type activity, activity with delta-valerolactone is 13% of wild-type activity, activity with gamma-nonalactone is 22% of wild-type activity. kcat/Km for delta-valerolactone is 11% of wild-type value, kcat/Km for gamma-nonalactone is 8% of wild-type value, kcat/Km for gamma-caprolactone is 19% of wild-type value, kcat/Km for 5-(thiobutyl)butyrolactone is 6.5% of wild-type value. Mutant with reduced lactonase activity, exhibits reduced or no biological function in ex vivo assay | Homo sapiens |
| H184Q | activity with dicoumarin is 57% compared to wild-type activity, activity with delta-valerolactone is 44% of wild-type activity, activity with gamma-nonalactone is 44% of wild-type activity | Homo sapiens |
| H184T | activity with dicoumarin is 17% compared to wild-type activity, activity with delta-valerolactone is 35% of wild-type activity, activity with gamma-nonalactone is 39% of wild-type activity | Homo sapiens |
| H285Q | activity with dicoumarin is 22% compared to wild-type activity, activity with delta-valerolactone is 20% of wild-type activity, activity with gamma-nonalactone is 38% of wild-type activity | Homo sapiens |
| H285S | activity with dicoumarin is 13% compared to wild-type activity, activity with delta-valerolactone is 8% of wild-type activity, activity with gamma-nonalactone is 16% of wild-type activity | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.27 | - |
5-(thiobutyl)butyrolactone | pH 8.0, wild-type enzyme | Homo sapiens |  |
| 0.39 | - |
gamma-nonalactone | pH 8.0, wild-type enzyme | Homo sapiens | |
| 0.57 | - |
delta-valerolactone | pH 8.0, wild-type enzyme | Homo sapiens | |
| 0.68 | - |
5-(thiobutyl)butyrolactone | pH 8.0, mutant enzyme H134Q | Homo sapiens | |
| 0.89 | - |
gamma-nonalactone | pH 8.0, mutant enzyme H134Q | Homo sapiens | |
| 0.95 | - |
delta-valerolactone | pH 8.0, mutant enzyme H134Q | Homo sapiens | |
| 1 | - |
Gamma-caprolactone | pH 8.0, wild-type enzyme | Homo sapiens | |
| 1.54 | - |
gamma-nonalactone | pH 8.0, mutant enzyme H115Q | Homo sapiens | |
| 1.6 | - |
5-(thiobutyl)butyrolactone | pH 8.0, mutant enzyme H115Q | Homo sapiens | |
| 1.83 | - |
5-(thiobutyl)butyrolactone | pH 8.0, mutant enzyme H115Q/H134Q | Homo sapiens | |
| 2.97 | - |
Gamma-caprolactone | pH 8.0, mutant enzyme H134Q | Homo sapiens | |
| 3.8 | - |
Gamma-caprolactone | pH 8.0, mutant enzyme H115Q | Homo sapiens | |
| 8.5 | - |
delta-valerolactone | pH 8.0, mutant enzyme H115Q | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| additional information | high density lipoprotein-associated enzyme | Homo sapiens | - |
- |
| additional information | high density lipoprotein-associated enzyme | Oryctolagus cuniculus | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | Asp269 and Glu53 participate in the ligation of catalytic Ca2+ | Homo sapiens | |
| Ca2+ | Asp269 and Glu53 participate in the ligation of catalytic Ca2+ | Oryctolagus cuniculus | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P27169 | - |
- |
| Oryctolagus cuniculus | Q9BGN0 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| wild-type-like rePON1-G2E6 and its various mutants are expressed as fusion proteins with thioredoxin and His6 tags | Homo sapiens |
| wild-type-like rePON1-G2E6 and its various mutants are expressed as fusion proteins with thioredoxin and His6 tags | Oryctolagus cuniculus |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5-(thiobutyl)butyrolactone + H2O | the lactonase and the esterase activity of PON1 is mediated by the His115-His134 | Homo sapiens | ? | - |
? | |
| 5-(thiobutyl)butyrolactone + H2O | the lactonase and the esterase activity of PON1 is mediated by the His115-His134 dyad | Oryctolagus cuniculus | ? | - |
? | |
| 5-(thioethyl)butyrolactone + H2O | the lactonase and the esterase activity of PON1 is mediated by the His115-His134 dyad | Oryctolagus cuniculus | ? | - |
? | |
| delta-valerolactone + H2O | - |
Homo sapiens | 5-hydroxypentanoic acid | - |
? | |
| delta-valerolactone + H2O | - |
Oryctolagus cuniculus | 5-hydroxypentanoic acid | - |
? | |
| dihydrocoumarin + H2O | - |
Homo sapiens | 3-(2-hydroxyphenyl)propanoic acid | - |
? | |
| gamma-caprolactone + H2O | - |
Homo sapiens | 4-hydroxyhexanoic acid | - |
? | |
| gamma-nonalactone + H2O | - |
Homo sapiens | 4-hydroxynonanoic acid | - |
? | |
| gamma-nonalactone + H2O | - |
Oryctolagus cuniculus | 4-hydroxynonanoic acid | - |
? | |
| gamma-undecanoic lactone + H2O | - |
Oryctolagus cuniculus | 4-hydroxyundecanoic acid | - |
? | |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.38 | - |
gamma-nonalactone | pH 8.0, mutant enzyme H115Q | Homo sapiens | |
| 1.74 | - |
5-(thiobutyl)butyrolactone | pH 8.0, mutant enzyme H115Q/H134Q | Homo sapiens | |
| 2.27 | - |
Gamma-caprolactone | pH 8.0, mutant enzyme H115Q | Homo sapiens | |
| 5.57 | - |
gamma-nonalactone | pH 8.0, mutant enzyme H134Q | Homo sapiens | |
| 7.5 | - |
5-(thiobutyl)butyrolactone | pH 8.0, mutant enzyme H115Q | Homo sapiens | |
| 19.4 | - |
5-(thiobutyl)butyrolactone | pH 8.0, mutant enzyme H134Q | Homo sapiens | |
| 25 | - |
Gamma-caprolactone | pH 8.0, mutant enzyme H134Q | Homo sapiens | |
| 31 | - |
gamma-nonalactone | pH 8.0, wild-type enzyme | Homo sapiens | |
| 40 | - |
delta-valerolactone | pH 8.0, mutant enzyme H134Q | Homo sapiens | |
| 44 | - |
Gamma-caprolactone | pH 8.0, wild-type enzyme | Homo sapiens | |
| 69.4 | - |
delta-valerolactone | pH 8.0, mutant enzyme H115Q | Homo sapiens | |
| 116 | - |
5-(thiobutyl)butyrolactone | pH 8.0, wild-type enzyme | Homo sapiens | |
| 210 | - |
delta-valerolactone | pH 8.0, wild-type enzyme | Homo sapiens | |
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