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Literature summary extracted from
- Modulating carnitine levels by targeting its biosynthesis pathway - selective inhibition of gamma-butyrobetaine hydroxylase (2014), Chem. Sci., 5, 1765-1771 .
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 1.14.11.1 | analysis of a crystal structure of human BBOX in complex with inhibitor AR692B and Ni2+ (an Fe2+ surrogate), P212121 space group, 2.8 A resolution | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.11.1 | 3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate | - |
Homo sapiens |  |
| 1.14.11.1 | 3-hydroxy-N-(2-phenylethyl)pyridine-2-carboxamide | weak inhibition | Homo sapiens | |
| 1.14.11.1 | AR692 | - |
Homo sapiens | |
| 1.14.11.1 | AR692B | a potent and selective inhibitor for human enzyme BBOX, binds in two modes, one of which adopts an unusual U-shape conformation stabilised by inter- and intra-molecular Pi-stacking interactions. Conformational changes observed on binding of the inhibitor to BBOX likely reflect those occurring in catalysis. The BBOX-AR692B with and without substrate/ inhibitor crystal structures (PDB ID 3O2G/3N6W) reveal substantial conformational differences | Homo sapiens | |
| 1.14.11.1 | AR780 | - |
Homo sapiens | |
| 1.14.11.1 | gamma-butyrobetaine | GBB, substrate inhibition at high concentrations | Homo sapiens | |
| 1.14.11.1 | mildronate | both a relatively weak BBOX inhibitor in vitro and a competitive substrate producing multiple products. The mode of action of mildronate may be nonselective | Homo sapiens | |
| 1.14.11.1 | additional information | identification of selective BBOX inhibitors, active against both isolated enzyme and in cells, docking study, overview. The identified template BBOX inhibitor binds to the active site iron via its carbonyl group and either its pyridine-nitrogen or C-3 hydroxyl group, the pyridine-nitrogen, C-3 hydroxyl group and side chain carboxylate are essential for binding. Examination of scaffolds with bicyclic aromatic rings, i.e. with quinoline and isoquinoline derivatives substituting for the (hydroxyl)pyridine ring reveal that quinolines have rather weak potency, while isoquinolines are relatively good inhibitors with the IC50 values in the low micromolar range. In the isoquinoline series, C-alpha side chains with the (S)-stereochemistry are preferred over those with the (R)-stereochemistry. In contrast to the pyridine series small side chains are preferred with the hydroxy-isoquinolines, with the methyl group having the best inhibitory properties | Homo sapiens | |
| 1.14.11.1 | N-(2-hydroxybenzoyl)-L-phenylalanine | - |
Homo sapiens | |
| 1.14.11.1 | N-(2-hydroxybenzoyl)glycine | weak inhibition | Homo sapiens | |
| 1.14.11.1 | N-(3-hydroxypyridine-2-carbonyl)-beta-alanine | weak inhibition | Homo sapiens | |
| 1.14.11.1 | N-(3-hydroxypyridine-2-carbonyl)-D-phenylalanine | weak inhibition | Homo sapiens | |
| 1.14.11.1 | N-(3-hydroxypyridine-2-carbonyl)-L-glutamic acid | - |
Homo sapiens | |
| 1.14.11.1 | N-(3-hydroxypyridine-2-carbonyl)-L-phenylalanine | - |
Homo sapiens | |
| 1.14.11.1 | N-(3-hydroxypyridine-2-carbonyl)glycine | weak inhibition | Homo sapiens | |
| 1.14.11.1 | N-(pyridine-2-carbonyl)-L-phenylalanine | - |
Homo sapiens | |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.11.1 | Fe2+ | dependent on, required for catalysis, bound to the active site | 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 | - |
- |
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 | mildronate + O2 | both a relatively weak BBOX inhibitor in vitro and a competitive substrate producing multiple products | Homo sapiens | ? | - |
? | |
Subunits
| EC Number | Subunits | Comment | Organism |
|---|---|---|---|
| 1.14.11.1 | homodimer | - |
Homo sapiens |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.14.11.1 | BBOX | - |
Homo sapiens |
| 1.14.11.1 | gamma-butyrobetaine hydroxylase | - |
Homo sapiens |
IC50 Value
| EC Number | IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|---|
| 1.14.11.1 | 0.000153 | - |
pH and temperature not specified in the publication | Homo sapiens | AR692B | |
| 1.14.11.1 | 0.0005 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(3-hydroxypyridine-2-carbonyl)-L-phenylalanine | |
| 1.14.11.1 | 0.0018 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(3-hydroxypyridine-2-carbonyl)-L-glutamic acid | |
| 1.14.11.1 | 0.002 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(3-hydroxypyridine-2-carbonyl)-L-phenylalanine | |
| 1.14.11.1 | 0.006 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(3-hydroxypyridine-2-carbonyl)glycine | |
| 1.14.11.1 | 0.0125 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(pyridine-2-carbonyl)-L-phenylalanine | |
| 1.14.11.1 | 0.06 | - |
pH and temperature not specified in the publication | Homo sapiens | mildronate | |
| 1.14.11.1 | 0.088 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(2-hydroxybenzoyl)-L-phenylalanine | |
| 1.14.11.1 | 0.15 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(3-hydroxypyridine-2-carbonyl)-D-phenylalanine | |
| 1.14.11.1 | 0.522 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(3-hydroxypyridine-2-carbonyl)-beta-alanine | |
| 1.14.11.1 | 0.537 | - |
pH and temperature not specified in the publication | Homo sapiens | N-(2-hydroxybenzoyl)glycine | |
| 1.14.11.1 | 1 | - |
above, pH and temperature not specified in the publication | Homo sapiens | 3-hydroxy-N-(2-phenylethyl)pyridine-2-carboxamide | |
| 1.14.11.1 | 1 | - |
above, pH and temperature not specified in the publication | Homo sapiens | N-(3-hydroxypyridine-2-carbonyl)glycine | |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.14.11.1 | evolution | the enzyme belongs to the superfamily of Fe(II) and 2OG dependent dioxygenases | Homo sapiens |
| 1.14.11.1 | metabolism | gamma-butyrobetaine hydroxylase (BBOX) catalyses the final step of carnitine biosynthesis | Homo sapiens |
| 1.14.11.1 | physiological function | enzyme BBOX catalyses the stereospecific C-3 hydroxylation of gamma-butyrobetaine (GBB) to give L-carnitine | Homo sapiens |
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