Literature summary extracted from
Tars, K.; Rumnieks, J.; Zeltins, A.; Kazaks, A.; Kotelovica, S.; Leonciks, A.; Sharipo, J.; Viksna, A.; Kuka, J.; Liepinsh, E.; Dambrova, M.
Crystal structure of human gamma-butyrobetaine hydroxylase (2010), Biochem. Biophys. Res. Commun., 398, 634-639.
Cloned(Commentary)
EC Number |
Cloned (Comment) |
Organism |
---|
1.14.11.1 |
expression of His-tagged GBBH in Escherichia coli strain WK6 |
Homo sapiens |
Crystallization (Commentary)
EC Number |
Crystallization (Comment) |
Organism |
---|
1.14.11.1 |
purified recombinant His-tagged GBBH, and SeMet-labeled variant, by sitting drop vapor diffusion technique, mixing 0.001 ml of 7 mg/ml protein in 20 mM Tris-HCl, pH 8.0, with 0.001 ml of reservoir solution containing 1.2 M ammonium sulfate and 100 mM sodium acetate, pH 4.5. In co-crystallization trials with ligands, each ligand is added to the reservoir solution to a final concentration of 5 mM, X-ray diffraction structure determination and analysis at 2.0 A and 3.5 A resolution, respectively |
Homo sapiens |
Inhibitors
EC Number |
Inhibitors |
Comment |
Organism |
Structure |
---|
1.14.11.1 |
3-(2,2,2-trimethylhydrazinium propionate dihydrate) |
i.e. mildronate, a synthetic inhibitor of GBBH, is a non-hydroxylatable analog of gamma-butyrobetaine |
Homo sapiens |
|
1.14.11.1 |
4-Trimethylammoniobutanoate |
substrate inhibition at concentrations above 0.2 mM |
Homo sapiens |
|
KM Value [mM]
EC Number |
KM Value [mM] |
KM Value Maximum [mM] |
Substrate |
Comment |
Organism |
Structure |
---|
1.14.11.1 |
0.0275 |
- |
4-Trimethylammoniobutanoate |
pH 7.0, 37°C, recombinant enzyme |
Homo sapiens |
|
Metals/Ions
EC Number |
Metals/Ions |
Comment |
Organism |
Structure |
---|
1.14.11.1 |
Fe2+ |
Fe(II)-binding residues form a conserved His-X-Asp-Xn-His triad |
Homo sapiens |
|
1.14.11.1 |
Zn2+ |
quantitative determination of Zn2+ by atomic absorption spectrometry, zinc-binding site structure in the N-terminal domain of GBBH, overview |
Homo sapiens |
|
Natural Substrates/ Products (Substrates)
EC Number |
Natural Substrates |
Organism |
Comment (Nat. Sub.) |
Natural Products |
Comment (Nat. Pro.) |
Rev. |
Reac. |
---|
1.14.11.1 |
4-trimethylammoniobutanoate + 2-oxoglutarate + O2 |
Homo sapiens |
- |
3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2 |
- |
? |
|
Organism
EC Number |
Organism |
UniProt |
Comment |
Textmining |
---|
1.14.11.1 |
Homo sapiens |
O75936 |
- |
- |
Purification (Commentary)
EC Number |
Purification (Comment) |
Organism |
---|
1.14.11.1 |
recombinant His-tagged GBBH from Escherichia coli strain WK6 by nickel affinity chromatography |
Homo sapiens |
Substrates and Products (Substrate)
EC Number |
Substrates |
Comment Substrates |
Organism |
Products |
Comment (Products) |
Rev. |
Reac. |
---|
1.14.11.1 |
4-trimethylammoniobutanoate + 2-oxoglutarate + O2 |
- |
Homo sapiens |
3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2 |
- |
? |
|
1.14.11.1 |
4-trimethylammoniobutanoate + 2-oxoglutarate + O2 |
catalytic domain and active site structure, overview |
Homo sapiens |
3-hydroxy-4-trimethylammoniobutanoate + succinate + CO2 |
- |
? |
|
Subunits
EC Number |
Subunits |
Comment |
Organism |
---|
1.14.11.1 |
dimer |
the GBBH monomer consists of a catalytic double-stranded beta-helix domain, and a smaller N-terminal domain, the N-terminal domain of GBBH has a similar fold to the DUF971 superfamily. GBBH is dimeric in its biological state. the dimerization interface of GBBH is very different from that of related enzymes, three-dimensional structure, overview |
Homo sapiens |
Synonyms
EC Number |
Synonyms |
Comment |
Organism |
---|
1.14.11.1 |
gamma-butyrobetaine hydroxylase |
- |
Homo sapiens |
Temperature Optimum [°C]
EC Number |
Temperature Optimum [°C] |
Temperature Optimum Maximum [°C] |
Comment |
Organism |
---|
1.14.11.1 |
37 |
- |
assay at |
Homo sapiens |
pH Optimum
EC Number |
pH Optimum Minimum |
pH Optimum Maximum |
Comment |
Organism |
---|
1.14.11.1 |
7 |
- |
assay at |
Homo sapiens |
IC50 Value
EC Number |
IC50 Value |
IC50 Value Maximum |
Comment |
Organism |
Inhibitor |
Structure |
---|
1.14.11.1 |
0.062 |
- |
pH 7.0, 37°C, recombinant enzyme |
Homo sapiens |
3-(2,2,2-trimethylhydrazinium propionate dihydrate) |
|
General Information
EC Number |
General Information |
Comment |
Organism |
---|
1.14.11.1 |
evolution |
the GBBH residues involved in zinc binding are evolutionary conserved in all sequenced eukaryotes more complex than Caenorhabditis elegans |
Homo sapiens |
1.14.11.1 |
physiological function |
GBBH is a 2-ketoglutarate-dependent dioxygenase that catalyzes the biosynthesis of L-carnitine by hydroxylation of gamma-butyrobetaine. L-Carnitine is required for the transport of long-chain fatty acids into mitochondria for generating metabolic energy |
Homo sapiens |