Information on EC 2.8.1.8 - lipoyl synthase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
2.8.1.8
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RECOMMENDED NAME
GeneOntology No.
lipoyl synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
protein N6-(octanoyl)lysine + 2 sulfur-(sulfur carrier) + 2 S-adenosyl-L-methionine = protein N6-(lipoyl)lysine + 2 (sulfur carrier) + 2 L-methionine + 2 5'-deoxyadenosine
show the reaction diagram
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protein N6-(octanoyl)lysine + 2 sulfur-(sulfur carrier) + 2 S-adenosyl-L-methionine = protein N6-(lipoyl)lysine + 2 (sulfur carrier) + 2 L-methionine + 2 5'-deoxyadenosine
show the reaction diagram
mechanism: sulfur is first inserted at C6 of octanoyl substrate to form an enzyme bound intermediate. In a subsequent rate determining step, the second sulfur atom is inserted at C8, suggesting an energy profile of the reaction reflecting the relative bond strengths of the primary and secondary C-H bonds to be cleaved at C8 and C6, resp.
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PATHWAY
KEGG Link
MetaCyc Link
lipoate biosynthesis and incorporation (glycine cleavage system, yeast)
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lipoate biosynthesis and incorporation (pyruvate dehydrogenase and oxoglutarate dehydrogenase, yeast)
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lipoate biosynthesis and incorporation I
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lipoate biosynthesis and incorporation II
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lipoate biosynthesis and incorporation III (Bacillus)
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Lipoic acid metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
protein N6-(octanoyl)lysine:sulfur sulfurtransferase
This enzyme is a member of the 'AdoMet radical' (radical SAM) family, all members of which produce the 5'-deoxyadenosin-5'-yl radical and methionine from AdoMet [i.e. S-adenosylmethionine, or S-(5'-deoxyadenosin-5'-yl)methionine], by the addition of an electron from an iron-sulfur centre. The radical is converted into 5'-deoxyadenosine when it abstracts a hydrogen atom from C-6 and C-8, leaving reactive radicals at these positions so that they can add sulfur, with inversion of configuration [4]. This enzyme catalyses the final step in the de-novo biosynthesis of the lipoyl cofactor, with the other enzyme involved being EC 2.3.1.181, lipoyl(octanoyl) transferase. Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, as it converts apoprotein into the biologically active holoprotein. Examples of such lipoylated proteins include pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [2,5]. An alternative lipoylation pathway involves EC 2.7.7.63, lipoate---protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues) [7].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Lip1
Q9ZWT1
isoform
LipA
Q86G50
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LipA protein
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lipoate synthase
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CAS REGISTRY NUMBER
COMMENTARY
189398-80-9
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GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
Q9ZWT1
the knockout of isoform LIP1p is fatal for early embryo development
metabolism
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the enzyme is involved in lipoic acid synthesis
physiological function
Q9ZWT1
isoform LIP1 is indispensable for embryo development and essential for plastids
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + 2 L-methionine + 2 5'-deoxyadenosyl radicals
show the reaction diagram
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both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide
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-
?
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + 2 L-methionine + 5'-deoxyadenosyl radical
show the reaction diagram
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octanoylated pyruvate dehydrogenase E2 domain
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-
?
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + L-methionine + 5'-deoxyadenosyl radicals
show the reaction diagram
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lipoyl-bearing subunit of the glycine cleavage system (H-protein) is a substrate for LipA. 5'-deoxyadenosyl radical acts directly on the octanoyl substrate. 2 equivalents of S-adenosyl-L-methionine are cleaved irreversibly in forming 1 equivalent of [lipoyl]H-protein and are consistent with a model in which two LipA proteins are required to synthesize one lipoyl group
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ir
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + L-methionine + 5'-deoxyadenosyl radicals
show the reaction diagram
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tetrapeptide substrate, containing an Nepsilon-octanoyl lysine residue, corresponding in sequence to the lipoyl binding domain of the E2 subunit of pyruvate dehydrogenase
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?
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + L-methionine + 5'-deoxyadenosine
show the reaction diagram
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?
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + L-methionine + 5'-deoxyadenosine
show the reaction diagram
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ir
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + L-methionine + 5'-deoxyadenosine
show the reaction diagram
Q9ZWT1
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-
?
additional information
?
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final step in de novo biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of pyruvate dehydrogenase (E2 domain)
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additional information
?
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insertion of sulfur into octanoyl groups is first at C6 to form an enzyme bound intermediate, and in a subsequent step a second sulfur is inserted at C8
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + L-methionine + 5'-deoxyadenosine
show the reaction diagram
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-
-
-
?
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + L-methionine + 5'-deoxyadenosine
show the reaction diagram
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-
-
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ir
protein N6-(octanoyl)lysine + sulfur + S-adenosyl-L-methionine
protein N6-(lipoyl)lysine + L-methionine + 5'-deoxyadenosine
show the reaction diagram
Q9ZWT1
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-
-
?
additional information
?
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final step in de novo biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of pyruvate dehydrogenase (E2 domain)
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COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
S-adenosyl-L-methionine
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METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Iron
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iron-sulfur protein. Presence of [3Fe-4S] and/or [4Fe-4S]clusters in both monomeric and dimeric LipA
Iron
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presence of a (2Fe-2S) center per protein. These clusters are converted to (4Fe-4S) centers during reduction under anaerobic conditions
Iron
Q86G50
[Fe-S] protein
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
43300
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monomer, gel filtration
84600
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dimer, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
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x * 36000, SDS-PAGE
additional information
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enzyme is isolated as a micture of 70% monomer and 30% dimer
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
C-terminally His-tagged protein
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wild-type and hexahistidine-tagged LipA
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Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
coexpression of lipA with groESL, trxA, or fragments of the isc operon such as iscSUA orhscBAfdx does not improve expression levels of soluble holo-LipA. Coexpression of lipA with iscSUA and hscBAfdx on a multi-cistronic plasmid does improve the expression of soluble LipAH and increases the molar ratios of iron and sulfide per LipAH
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expression in Escherichia coli
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