Cloned (Comment) | Organism |
---|---|
construction and expression of the C-terminal 87 amino acids of biotin carboxyl carrier protein, i.e. BCCP-87. cross-species activity of BPLs permitts functional cloning of the cDNA for yeast BPL through genetic complementation with a conditional lethal birA- strain of Escherichia coli | Escherichia coli |
cross-species activity of BPLs permitts functional cloning of the cDNA for human BPL through genetic complementation with a conditional lethal birA? strain of Escherichia coli | Homo sapiens |
cross-species activity of BPLs permitts functional cloning of the cDNA for yeast BPL through genetic complementation with a conditional lethal birA? strain of Escherichia coli | Saccharomyces cerevisiae |
Crystallization (Comment) | Organism |
---|---|
EcBPL domains determination through X-ray crystallography at 2.3 A resolution, and determination of the crystal structure of EcBPL in complex with biotin | Escherichia coli |
PhBPL in complex with biotin, ATP and biotinyl-5'-AMP, X-ray diffraction and structure analysis at 1.6 A, 1.6 A, 1.45 A resolution, respectively. Structure-function relationship, modelling, overview | Pyrococcus horikoshii |
Protein Variants | Comment | Organism |
---|---|---|
D571N | naturally occuring mutation, important in positioning K579 in the AMP binding site | Homo sapiens |
D615Y | naturally occuring mutation in the loop between alpha3 and beta6 that cover AMP, may coordinate oxygens of the AMP phosphate | Homo sapiens |
D634Y | naturally occuring mutation of a solvent exposed residue, distal to active site on alpha4 and alpha5, respectively | Homo sapiens |
D715G | naturally occuring mutation on beta9, may be involved in capping and stabilising the catalytic domain structure | Homo sapiens |
G518E | naturally occuring mutation close to the active site and part of the ligand-binding loop, the mutation may not allow as much flexibility of this loop. As part of the hydrophobic pocket, making this polar residue would perturb biotin binding | Homo sapiens |
G581S | naturally occuring mutation of a residue involved in hydrophobic interactions with biotin in the binding pocket | Homo sapiens |
G582R | naturally occuring mutation of a residue involved in hydrophobic interactions with biotin in the binding pocket | Homo sapiens |
L237P | the mutant shows reduced catalytic activity compared to the wild-type enzyme | Escherichia coli |
L470S | naturally occuring mutation in an unstructured loop distal to the ligand-binding site | Homo sapiens |
additional information | HCS mutants with deletions up to Ala235 or Thr266 still show catalytic activity and can complement an enzyme-deficient Escherichia coli birA- strain. Enzyme deficiency can cause symptoms like ketoacidosis, feeding difficulties, hypotonia, seizures, developmental delay and dermal abnormalities such as rashes, dryness of the skin and alopecia, multiple carboxylase deficiency is caused by a lack of activity of the biotin-dependent enzymes, phenotypes, overview. Molecular modelling of mutations causing HCS deficiency, detailed overview | Homo sapiens |
additional information | mutational analysis, overview. The C-terminal 87 amino acids of biotin carboxyl carrier protein, i.e. BCCP-87, are recognised and biotinylated by BPL as well as full-length BCCP due to the fact that this peptide adopts the tertiary structure that is required for the interaction with BPL | Escherichia coli |
R118G | mutation of Arg118 to glycine in EcBPL causes altered affinity of BPL for biotin, increased dissociation rates for biotin and biotinyl-5'-AMP, and consequently, promiscuous biotinylation of inappropriate proteins | Escherichia coli |
R508W/N511K | naturally occuring mutation of a residue critical in loop covering the ligand-binding site. R508 co-ordinates to the backbone carbonyl N712 to form a salt bridge, removing this would result in a more flexible loop, analogous to EcBPL R118 and R121 that co-ordinate oxygens within the AMP phosphate group | Homo sapiens |
T462I | naturally occuring mutation in an unstructured loop distal to the ligand-binding site | Homo sapiens |
V547G | naturally occuring mutation of a buried hydrophobic residue in alpha2 that reside near the AMP-binding beta5 strand | Homo sapiens |
V550M | naturally occuring mutation of a buried hydrophobic residue in alpha2 that reside near the AMP-binding beta5 strand | Homo sapiens |
Y456C | naturally occuring mutation in an unstructured loop distal to the ligand-binding site | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | - |
Homo sapiens | 5737 | - |
mitochondrial membrane | - |
Homo sapiens | 31966 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Homo sapiens | |
Mg2+ | - |
Saccharomyces cerevisiae | |
Mg2+ | - |
Pyrococcus horikoshii | |
Mg2+ | - |
Escherichia coli |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
265000 | - |
acetyl-CoA carboxylase-1 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | Pyrococcus horikoshii | - |
AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | Homo sapiens | activation by biotinylation, HCS is the enzyme responsible for specifically attaching biotin onto the mammalian biotin domains. Biotinylation is catalysed through a two-step reaction where biotin is first activated to biotinyl-5'-AMP in an ATP-dependent manner, the biotin is then transferred onto the epsilon-amino group of a specific target lysine residue. All biotin-dependent enzymes utilise the enzyme-bound biotin group for the transfer of CO2 between metabolites | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | Saccharomyces cerevisiae | all biotin-dependent enzymes utilise the enzyme-bound biotin group for the transfer of CO2 between metabolites | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | Escherichia coli | the holo-enzyme is a multienzyme complex, in which biotin is bound to the biotin carboxyl carrier protein, binding structure, overview. All biotin-dependent enzymes utilise the enzyme-bound biotin group for the transfer of CO2 between metabolites | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | Pyrococcus horikoshii OT-3 | - |
AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
additional information | Homo sapiens | acetyl-CoA carboxylase-1 and -2 perform the essential role of converting acetyl CoA to malonyl CoA, the first committed step in fatty acid synthesis, required for membrane biogenesis. The enzyme exists either as catalytic homodimers or associated with more highly active filamentous fibres. Development of an assay method using apo-pyruvate carboxylase partially purified from the livers of biotin-deficient rats for detection of biotin in fibroblast samples from healthy persons and patients with multiple carboxylase deficiency | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | P06709 | - |
- |
Homo sapiens | - |
- |
- |
Pyrococcus horikoshii | - |
strain OT3 | - |
Pyrococcus horikoshii OT-3 | - |
strain OT3 | - |
Saccharomyces cerevisiae | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
fibroblast | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
Saccharomyces cerevisiae | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
Pyrococcus horikoshii | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | activation by biotinylation, HCS is the enzyme responsible for specifically attaching biotin onto the mammalian biotin domains. Biotinylation is catalysed through a two-step reaction where biotin is first activated to biotinyl-5'-AMP in an ATP-dependent manner, the biotin is then transferred onto the epsilon-amino group of a specific target lysine residue. All biotin-dependent enzymes utilise the enzyme-bound biotin group for the transfer of CO2 between metabolites | Homo sapiens | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | all biotin-dependent enzymes utilise the enzyme-bound biotin group for the transfer of CO2 between metabolites | Saccharomyces cerevisiae | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | the holo-enzyme is a multienzyme complex, in which biotin is bound to the biotin carboxyl carrier protein, binding structure, overview. All biotin-dependent enzymes utilise the enzyme-bound biotin group for the transfer of CO2 between metabolites | Escherichia coli | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | activation by biotinylation. The biotinylated lysine itself is located in a hairpin turn between beta-strands 4 and 5 in the centre of the polypeptide, present in a Met-Lys-Met motif that is essentially invariant in all biotin domains. HCS may well contain proofreading activity to select appropriate substrates | Homo sapiens | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | conformational changes occur upon biotin binding. Structure-function relationship, modelling, overview | Escherichia coli | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | structure-function relationship, modelling, overview | Pyrococcus horikoshii | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
Pyrococcus horikoshii OT-3 | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | structure-function relationship, modelling, overview | Pyrococcus horikoshii OT-3 | AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] | - |
? | |
additional information | acetyl-CoA carboxylase-1 and -2 perform the essential role of converting acetyl CoA to malonyl CoA, the first committed step in fatty acid synthesis, required for membrane biogenesis. The enzyme exists either as catalytic homodimers or associated with more highly active filamentous fibres. Development of an assay method using apo-pyruvate carboxylase partially purified from the livers of biotin-deficient rats for detection of biotin in fibroblast samples from healthy persons and patients with multiple carboxylase deficiency | Homo sapiens | ? | - |
? | |
additional information | protein-protein interaction between BPL and biotin-dependent enzymes is highly conserved. substrate recognition by BPLs occurs through conserved structural cues that govern the specificity of biotinylation, molecular modelling, overview. The region between Leu166 and Arg290 of BPL is required for catalysis. Development of an assay method using apo-pyruvate carboxylase partially purified from the livers of biotin-deficient rats for detection of biotin in samples from healthy persons and patients with multiple carboxylase deficiency | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | dimerization upon biotin binding | Escherichia coli |
dimer | the protein is a constitutive dimer, i.e. dimerises independently of biotin binding | Pyrococcus horikoshii |
More | EcBPL contains three distinct domains determined through X-ray crystallography. Monomeric and dimeric forms of the enzyme are involved in enzyme regulation, overview. Structure-function relationship, overview. EcBPL contains a DNA binding motif | Escherichia coli |
More | PhBPL does not contain a DNA binding motif | Pyrococcus horikoshii |
More | structure-activity molecular modelling. Acetyl-CoA carboxylase-1 exists either as catalytic homodimers or associated with more highly active filamentous fibres. The region between Leu166 and Arg290 is required for catalysis | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
biotin protein ligase | - |
Homo sapiens |
biotin protein ligase | - |
Saccharomyces cerevisiae |
biotin protein ligase | - |
Pyrococcus horikoshii |
biotin protein ligase | - |
Escherichia coli |
BPL | - |
Homo sapiens |
BPL | - |
Saccharomyces cerevisiae |
BPL | - |
Pyrococcus horikoshii |
BPL | - |
Escherichia coli |
HCS | - |
Homo sapiens |
HCS | - |
Saccharomyces cerevisiae |
HCS | - |
Escherichia coli |
Holocarboxylase synthetase | - |
Homo sapiens |
Holocarboxylase synthetase | - |
Saccharomyces cerevisiae |
Holocarboxylase synthetase | - |
Escherichia coli |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens | |
ATP | - |
Saccharomyces cerevisiae | |
ATP | - |
Pyrococcus horikoshii | |
ATP | - |
Escherichia coli | |
biotin | - |
Pyrococcus horikoshii | |
biotin | bound to the biotin domain, structure, overview | Homo sapiens | |
biotin | bound to the biotin domain, structure, overview | Saccharomyces cerevisiae | |
biotin | bound to the biotin domain, structure, overview | Escherichia coli |