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Literature summary for 6.3.4.15 extracted from

  • Pendini, N.R.; Bailey, L.M.; Booker, G.W.; Wilce, M.C.; Wallace, J.C.; Polyak, S.W.
    Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency (2008), Biochim. Biophys. Acta, 1784, 973-982.
    View publication on PubMed

Cloned(Commentary)

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 (Commentary)

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

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

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
Homo sapiens 5737
-
mitochondrial membrane
-
Homo sapiens 31966
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
Homo sapiens
Mg2+
-
Saccharomyces cerevisiae
Mg2+
-
Pyrococcus horikoshii
Mg2+
-
Escherichia coli

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
265000
-
acetyl-CoA carboxylase-1 Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Escherichia coli P06709
-
-
Homo sapiens
-
-
-
Pyrococcus horikoshii
-
strain OT3
-
Pyrococcus horikoshii OT-3
-
strain OT3
-
Saccharomyces cerevisiae
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
fibroblast
-
Homo sapiens
-

Substrates and Products (Substrate)

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

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

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

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