Activating Compound | Comment | Organism | Structure |
---|---|---|---|
ascorbate | required | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
recombinant expression of His6-tagged enzyme in Saccharomyces cerevisiae strain AH22 | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
purified recombinant enzyme in complex with inhibitors 4-(ethyldimethylammonio)butanoate, 3-carboxy-N-(2-fluoroethyl)-N,N-dimethylpropan-1-aminium, 1-(3-carboxypropyl)-1-methylpyrrolidin-1-ium, 4-(trimethylammonio)pentanoate, [3-(trimethylammonio)propyl]phosphinate, and 3-(1,1,1,2-tetramethylhydrazin-1-ium-2-yl)propanoate, sitting drop vapor technique, mixing of 0.001 ml of 7 mg/ml protein, 8 mM N-oxalylglycine and 4 mM inhibitor, with 0.001 ml of well solution containing 0.2 M ammonium citrate, 20% PEG 3350, 3% hexanediamine, and 10 mM ZnSO4, pH 7.0, X-ray diffraction structure determination and analysis at 1.70-2.40 A resolution | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(E)-4-(trimethylammonio)but-2-enoate | - |
Homo sapiens | |
1,1,1-trimethyl-2-(2-phosphonoethyl)hydrazin-1-ium Iodide | - |
Homo sapiens | |
1-(3-carboxypropyl)-1-methylpyrrolidin-1-ium | - |
Homo sapiens | |
1-(3-carboxypropyl)pyrrolidin-1-ium | - |
Homo sapiens | |
2-(1,1,1-trimethylhydrazin-1-ium-2-yl)ethanesulfonate | - |
Homo sapiens | |
2-(2-carboxyethyl)-1,1-diethyl-1-methylhydrazin-1-ium chloride | - |
Homo sapiens | |
2-(2-carboxyethyl)-1,1-dimethyl-1-(prop-2-yn-1-yl)-hydrazin-1-ium bromide | - |
Homo sapiens | |
2-(2-carboxyethyl)-1-(2-chloroethyl)-1,1-dimethylhydrazin-1-ium bromide | - |
Homo sapiens | |
3-(1,1,1,2-tetramethylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens | |
3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate | i.e. mildronate, a clinically used and approved drug, but weak inhibitor. Enzyme-inhibitor interactions from structure PDB ID 3O2G | Homo sapiens | |
3-(1,1,2-trimethyl-1-propylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens | |
3-(1,1-dimethyl-1-vinylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens | |
3-(1-allyl-1,1-dimethylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens | |
3-(1-ethyl-1,1,2-trimethylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens | |
3-(1-ethyl-1,1-dimethylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens | |
3-(1-isopropyl-1,1-dimethylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens | |
3-(2-ethyl-1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens | |
3-(ethyldimethylammonio)propane-1-sulfonate | - |
Homo sapiens | |
3-(trimethylammonio)cyclohexanecarboxylate | - |
Homo sapiens | |
3-(trimethylammonio)propane-1-sulfonate | - |
Homo sapiens | |
3-carboxy-2-chloro-N,N,N-trimethylpropan-1-aminium | - |
Homo sapiens | |
3-carboxy-N-(2-chloroethyl)-N,N-dimethylpropan-1-aminium | - |
Homo sapiens | |
3-carboxy-N-(2-fluoroethyl)-N,N-dimethylpropan-1-aminium | - |
Homo sapiens | |
3-[1-(2-aminoethyl)-1,1-dimethylhydrazin-1-ium-2-yl]-propanoate | - |
Homo sapiens | |
3-[1-(2-hydroxyethyl)-1,1-dimethylhydrazin-1-ium-2-yl]-propanoate | - |
Homo sapiens | |
4-(allyldimethylammonio)butanoate | - |
Homo sapiens | |
4-(benzyldimethylammonio)butanoate | - |
Homo sapiens | |
4-(butyldimethylammonio)butanoate | - |
Homo sapiens | |
4-(cyclobutyldimethylammonio)butanoate | - |
Homo sapiens | |
4-(cyclopentyldimethylammonio)butanoate | - |
Homo sapiens | |
4-(cyclopropyldimethylammonio)butanoate | - |
Homo sapiens | |
4-(dimethylsulfonio)butanoate | - |
Homo sapiens | |
4-(ethyldimethylammonio)butanoate | - |
Homo sapiens | |
4-(trimethylammonio)pentanoate | - |
Homo sapiens | |
4-[(2-hydroxyethyl)dimethylammonio]butanoate | - |
Homo sapiens | |
4-[(bromomethyl)dimethylammonio]butanoate | - |
Homo sapiens | |
4-[(chloromethyl)dimethylammonio]butanoate | - |
Homo sapiens | |
4-[(cyclobutylmethyl)dimethylammonio]butanoate | - |
Homo sapiens | |
4-[(cyclopropylmethyl)dimethylammonio]butanoate | - |
Homo sapiens | |
4-[(iodomethyl)dimethylammonio]butanoate | - |
Homo sapiens | |
4-[(methoxymethyl)dimethylammonio]butanoate | - |
Homo sapiens | |
4-[diethyl(methyl)ammonio]butanoate | - |
Homo sapiens | |
4-[dimethyl(prop-2-yn-1-yl)ammonio]butanoate | - |
Homo sapiens | |
4-[dimethyl(propyl)ammonio]butanoate | - |
Homo sapiens | |
4-[dimethyl(vinyl)ammonio]butanoate | - |
Homo sapiens | |
4-[isopropyl(dimethyl)ammonio]butanoate | - |
Homo sapiens | |
5-(trimethylammonio)pentanoate | - |
Homo sapiens | |
gamma-butyrobetaine | substrate inhibition at high concentrations. Enzyme-inhibitor interactions from structure PDB ID 3MS5 | Homo sapiens | |
additional information | discovery of inhibitors of gamma-butyrobetaine hydroxylase, design, synthesis, and properties of 51 compounds, which include both gamma-butyrobetaine and mildronate analogues, structure-activity relationships, overview | Homo sapiens | |
N,N,N-trimethyl-3-(1H-tetrazol-5-yl)propan-1-aminium | - |
Homo sapiens | |
N,N,N-trimethyl-3-phosphonopropan-1-aminium | - |
Homo sapiens | |
N-(2-bromoethyl)-3-carboxy-N,N-dimethylpropan-1-aminium | - |
Homo sapiens | |
[3-(ethyldimethylammonio)propyl]phosphinate | - |
Homo sapiens | |
[3-(trimethylammonio)propyl]phosphinate | - |
Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | dependent on, required for catalysis | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
4-trimethylammoniobutanoate + 2-oxoglutarate + O2 | Homo sapiens | - |
3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O75936 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His6-tagged enzyme from Saccharomyces cerevisiae strain AH22 by nickel affinity chromatography, desalting gel filtration, anion exchange chromatography, tag cleavage by recombinant TEV protease, desalting gel filtration, and another step of nickel affinity chromatography to remove the His-tag | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
4-trimethylammoniobutanoate + 2-oxoglutarate + O2 | - |
Homo sapiens | 3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
BBOX | - |
Homo sapiens |
gamma-butyrobetaine hydroxylase | - |
Homo sapiens |
GBBH | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.016 | - |
3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate | pH 7.0, 37°C, recombinant enzyme | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00009 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(1,1,1,2-tetramethylhydrazin-1-ium-2-yl)propanoate | |
0.0001 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | N,N,N-trimethyl-3-phosphonopropan-1-aminium | |
0.00026 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-carboxy-N-(2-chloroethyl)-N,N-dimethylpropan-1-aminium | |
0.00049 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 1-(3-carboxypropyl)-1-methylpyrrolidin-1-ium | |
0.00052 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | [3-(trimethylammonio)propyl]phosphinate | |
0.00053 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | [3-(ethyldimethylammonio)propyl]phosphinate | |
0.00061 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-carboxy-N-(2-fluoroethyl)-N,N-dimethylpropan-1-aminium | |
0.00081 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(cyclobutyldimethylammonio)butanoate | |
0.0012 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | N-(2-bromoethyl)-3-carboxy-N,N-dimethylpropan-1-aminium | |
0.0014 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[dimethyl(prop-2-yn-1-yl)ammonio]butanoate | |
0.0017 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(trimethylammonio)propane-1-sulfonate | |
0.0021 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(cyclopropyldimethylammonio)butanoate | |
0.0027 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(allyldimethylammonio)butanoate | |
0.0028 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(2-ethyl-1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate | |
0.0031 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(1,1,2-trimethyl-1-propylhydrazin-1-ium-2-yl)propanoate | |
0.0033 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(ethyldimethylammonio)butanoate | |
0.0038 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | (E)-4-(trimethylammonio)but-2-enoate | |
0.0057 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[isopropyl(dimethyl)ammonio]butanoate | |
0.0067 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(ethyldimethylammonio)propane-1-sulfonate | |
0.0068 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(1,1-dimethyl-1-vinylhydrazin-1-ium-2-yl)propanoate | |
0.0072 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(1-ethyl-1,1,2-trimethylhydrazin-1-ium-2-yl)propanoate | |
0.0102 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 2-(2-carboxyethyl)-1-(2-chloroethyl)-1,1-dimethylhydrazin-1-ium bromide | |
0.024 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 2-(2-carboxyethyl)-1,1-dimethyl-1-(prop-2-yn-1-yl)-hydrazin-1-ium bromide | |
0.087 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 2-(1,1,1-trimethylhydrazin-1-ium-2-yl)ethanesulfonate | |
0.1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[diethyl(methyl)ammonio]butanoate | |
0.117 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 1,1,1-trimethyl-2-(2-phosphonoethyl)hydrazin-1-ium Iodide | |
0.119 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(1-allyl-1,1-dimethylhydrazin-1-ium-2-yl)propanoate | |
0.127 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[dimethyl(vinyl)ammonio]butanoate | |
0.14 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(1-ethyl-1,1-dimethylhydrazin-1-ium-2-yl)propanoate | |
0.268 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[(chloromethyl)dimethylammonio]butanoate | |
0.343 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(trimethylammonio)pentanoate | |
0.388 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(dimethylsulfonio)butanoate | |
0.459 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-carboxy-2-chloro-N,N,N-trimethylpropan-1-aminium | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 1-(3-carboxypropyl)pyrrolidin-1-ium | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 2-(2-carboxyethyl)-1,1-diethyl-1-methylhydrazin-1-ium chloride | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(1-isopropyl-1,1-dimethylhydrazin-1-ium-2-yl)propanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-(trimethylammonio)cyclohexanecarboxylate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-[1-(2-aminoethyl)-1,1-dimethylhydrazin-1-ium-2-yl]-propanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 3-[1-(2-hydroxyethyl)-1,1-dimethylhydrazin-1-ium-2-yl]-propanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(benzyldimethylammonio)butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(butyldimethylammonio)butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-(cyclopentyldimethylammonio)butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[(2-hydroxyethyl)dimethylammonio]butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[(bromomethyl)dimethylammonio]butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[(cyclobutylmethyl)dimethylammonio]butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[(cyclopropylmethyl)dimethylammonio]butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[(iodomethyl)dimethylammonio]butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[(methoxymethyl)dimethylammonio]butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 4-[dimethyl(propyl)ammonio]butanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | 5-(trimethylammonio)pentanoate | |
1 | - |
pH 7.0, 37°C, recombinant enzyme | Homo sapiens | N,N,N-trimethyl-3-(1H-tetrazol-5-yl)propan-1-aminium |
General Information | Comment | Organism |
---|---|---|
physiological function | gamma-butyrobetaine hydroxylase (BBOX) catalyzes the conversion of gamma butyrobetaine (GBB) to L-carnitine, which is involved in the generation of metabolic energy from long-chain fatty acids | Homo sapiens |