Information on EC 2.3.1.181 - lipoyl(octanoyl) transferase

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

EC NUMBER
COMMENTARY
2.3.1.181
-
RECOMMENDED NAME
GeneOntology No.
lipoyl(octanoyl) transferase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
an octanoyl-[acyl-carrier protein] + a protein = a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
-
-
-
an octanoyl-[acyl-carrier protein] + a protein = a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
enzyme functions as a cysteine/lysine dyad acyltransferase, where K142 and C176 are acid/base catalysts. Reaction proceeds via an internal thioester intermediate
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
Acyl group transfer
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
lipoate biosynthesis and incorporation (glycine cleavage system, yeast)
-
-
lipoate biosynthesis and incorporation I
-
-
lipoate biosynthesis and incorporation III (Bacillus)
-
-
lipoate biosynthesis
-
-
Lipoic acid metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
octanoyl-[acyl-carrier protein]:protein N-octanoyltransferase
This is the first committed step in the biosynthesis of lipoyl cofactor. 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) [2,3]. Lipoyl-ACP can also act as a substrate [4] although octanoyl-ACP is likely to be the true substrate [6] . The other enzyme involved in the biosynthesis of lipoyl cofactor is EC 2.8.1.8, lipoyl synthase. An alternative lipoylation pathway involves EC 2.7.7.63, lipoate---protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues).
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ACP: GcvH octanoyltransferase
-
-
ACP:protein-N-octanoyltransferase
-
-
LipB octanoyltransferase
-
-
LipM
-
gene name
lipoate/octanoate transferase
-
-
lipoyl (octanoyl)-acyl carrier protein:protein transferase
-
-
lipoyl(octanoyl) transferase
-
lipoyl(octanoyl)-[acyl-carrier-protein]-protein N-lipoyltransferase
-
-
lipoyl(octanoyl)transferase
-
-
lipoyltransferase
-
lipoyltransferase
-
-
octanoyl (lipoyl): N-octanoyl (lipoyl) transferase
-
-
octanoyl-acyl carrier protein:protein-N-octanoyltransferase
-
-
octanoyl-[acyl carrier protein {ACP}]:protein N-octanoyltransferase
-
-
octanoyl-[acyl carrier protein]-protein N-octanoyltransferase
-
-
octanoyl-[acyl carrier protein]:protein N-octanoyltransferase
-
-
octanoyltransferase LipM
-
-
CAS REGISTRY NUMBER
COMMENTARY
392687-64-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Columbia ecotype
-
-
Manually annotated by BRENDA team
wild type and several LipB knockout strains
-
-
Manually annotated by BRENDA team
enzyme is considerably upregulated in patients with multiple-drug-resistant Mycobacterium tuberculosis
Uniprot
Manually annotated by BRENDA team
enzyme is considerably upregulated in patients with multiple-drug-resistant Mycobacterium tuberculosis
Uniprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
LipM and LipL phylogenetic tree analysis, overview
malfunction
-
DELTAlipL strains are unable to synthesize lipoic acid despite the presence of LipM and the sulfur insertion enzyme, LipA, which should suffice for lipoic acid biosynthesis. Strain NM57 DELTAlipM is auxotrophic for lipoic acid when grown in minimal medium but grew as well as the wild type strain JH642 in the presence of lipoic acid
metabolism
-
The LipB octanoyltransferase catalyzes the first step of lipoic acid synthesis in Escherichia coli, transfer of the octanoyl moiety from octanoyl-acyl carrier protein to the lipoyl domains of the E2 subunits of the 2-oxoacid dehydrogenases of aerobic metabolism.
metabolism
-
The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite’s lipoic acid/octanoic acid ligases/transferases.
physiological function
-
LipB (EC 2.3.11.181) is responsible for octanoylation of the E2 components of 2-oxoacid dehydrogenases to provide the substrates of LipA (EC 2.7.7.63), an S-adenosyl-L-methionine radical enzyme that inserts two sulfur atoms into the octanoyl moiety to give the active lipoylated dehydrogenase complexes
physiological function
-
LipM is required for modification of lipoyl domains by the biosynthetic pathway, it is responsible for octanoyl transfer in vivo requirement for LipL. But LipM is only required for the endogenous lipoylation pathway, whereas LipL also plays a role in lipoic acid scavenging
physiological function
-
LipM specifically modifies the glycine cleavage system protein, GcvH. GcvH is required in Bacillus subtilis lipoic acid biosynthesis, overview. LipM is an octanoyltransferase required for lipoic acid synthesis, and LipL is essential for lipoic acid synthesis, but has no detectable octanoyltransferase or ligase activity either in vitro or in vivo, it catalyses the amidotransfer (transamidation) of the octanoyl moiety from octanoyl-glycine cleavage system protein to the E2 subunit of pyruvate dehydrogenase
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
an octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
-
-
?
an octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
LipM specifically modifies the glycine cleavage system protein, GcvH
-
?
an octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
acyl-enzyme intermediate mechanism
-
?
an octanoyl-[acyl-carrier protein] + glycine cleavage system protein
glycine cleavage system protein-N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
-
-
?
lipoyl-[acyl-carrier protein] + apo-pyruvate dehydrogenase protein
?
show the reaction diagram
-
-
-
-
?
octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
-
-
?
octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
LipB (EC 2.3.11.181) is responsible for octanoylation of the E2 components of 2-oxoacid dehydrogenases to provide the substrates of LipA (EC 2.7.7.63), an S-adenosyl-L-methionine radical enzyme that inserts two sulfur atoms into the octanoyl moiety to give the active lipoylated dehydrogenase complexes. LipB accumulates an octanoyl-enzyme intermediate with no sign of a lipoyl-enzyme intermediate, LipB (EC 2.3.11.181) is responsible for octanoylation of the E2 components of 2-oxoacid dehydrogenases to provide the substrates of LipA (EC 2.7.7.63), an S-adenosyl-L-methionine radical enzyme that inserts two sulfur atoms into the octanoyl moiety to give the active lipoylated dehydrogenase complexes. The binding sites for LipB reside both in the lipoyl domain and catalytic core sequences
-
?
octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
the transfer of the octanoyl group from octanoyl-ACP to Bacillus subtilis GcvH occurs in a LipM-dependent manner. The LipM reaction proceeds through a thioester-linked acyl enzyme intermediate. The LipM active site nucleophile is identified as C150
-
?
octanoyl-[acyl-carrier protein] + apo-E2 domain
apo E2-domain protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
reaction proceeds through an acyl-enzyme intermediate
-
?
octanoyl-[acyl-carrier protein] + apo-H protein
APO H-protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
LipB reaction represents the first committed step in the biosynthesis of the lipoyl cofactor. apo-H protein is the lipoyl bearing subunit of the glycine cleavage system
-
?
octanoyl-[acyl-carrier protein] + apo-H protein
apo-H protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
apo-H protein is the lipoyl bearing subunit of the glycine cleavage system
-
?
octanoyl-[acyl-carrier protein] + apo-pyruvate dehydogenase protein
apo-pyruvate dehydrogenase protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
-
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
-
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
-
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
first committed step in the biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of glycine cleavage system (H protein)
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
first committed step in the biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of pyruvate dehydrogenase (E2 domain)
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
first committed step in the biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of pyruvate dehydrogenase (E2 domain) and of the 2-oxoglutarate dehydrogenase complex
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + [acyl-carrier protein]
show the reaction diagram
-
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
an octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
-
-
?
an octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
LipM specifically modifies the glycine cleavage system protein, GcvH
-
?
an octanoyl-[acyl-carrier protein] + glycine cleavage system protein
glycine cleavage system protein-N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
-
-
?
octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
-
-
?
octanoyl-[acyl-carrier protein] + a protein
a protein N6-(octanoyl)lysine + an [acyl-carrier protein]
show the reaction diagram
-
LipB (EC 2.3.11.181) is responsible for octanoylation of the E2 components of 2-oxoacid dehydrogenases to provide the substrates of LipA (EC 2.7.7.63), an S-adenosyl-L-methionine radical enzyme that inserts two sulfur atoms into the octanoyl moiety to give the active lipoylated dehydrogenase complexes. LipB accumulates an octanoyl-enzyme intermediate with no sign of a lipoyl-enzyme intermediate
-
?
octanoyl-[acyl-carrier protein] + apo-H protein
APO H-protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
LipB reaction represents the first committed step in the biosynthesis of the lipoyl cofactor. apo-H protein is the lipoyl bearing subunit of the glycine cleavage system
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
-
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
first committed step in the biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of glycine cleavage system (H protein)
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
first committed step in the biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of pyruvate dehydrogenase (E2 domain)
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + acyl-carrier protein
show the reaction diagram
-
first committed step in the biosynthesis of lipoyl cofactor. The lipoyl cofactor is essential for the function of pyruvate dehydrogenase (E2 domain) and of the 2-oxoglutarate dehydrogenase complex
-
?
octanoyl-[acyl-carrier protein] + protein
protein N6-(octanoyl)lysine + [acyl-carrier protein]
show the reaction diagram
O46419
-
-
?
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Octanoyl-CoA
-
0.5 mM, 67% inhibition
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KHCO3
-
100 mM, slight activation
LipL
-
is essential for lipoic acid synthesis, but has no detectable octanoyltransferase or ligase activity either in vitro or in vivo. It catalyses the amidotransfer (transamidation) of the octanoyl moiety from octanoyl-GcvH to the E2 subunit of pyruvate dehydrogenase
-
NaOAc
-
100 mM, slight activation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0132
apo-H protein
-
pH 7.2, 37°C
-
0.001
lipoyl-[acyl-carrier protein]
-
-
0.0102
octanoyl-[acyl-carrier protein]
-
pH 7.2, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.2
apo-H protein
Escherichia coli
-
pH 7.2, 37°C
-
0.2
octanoyl-[acyl-carrier protein]
Escherichia coli
-
pH 7.2, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
-
assay at
7.8
assay of lipoylation
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
-
pH 6.0: about 65% of maximal activity, pH 9.0: about 40% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
assay of lipoylation
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10000
-
monomer, gel filtration
663308
14000
-
gel filtration
711217
26220
-
MALDI mass spectrometry
712504
29000
-
trimer, gel filtration
663308
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
-
1 * 14000, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the crystal structure of lipoyltransferase in complex with lipoyl-AMP is determined at a resolution of 2.1 A
enzyme shows thioether-linked active site complex with decanoic acid. Structural comparison with lipoate protein ligase A
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydroxylapatite and DEAE-Sepharose columns are used for the purification of the recombinant protein and for the purification of lipoyltransferase from bovine liver mitochondria
isolation and properties of a very stable complex between LipB and acyl cyrrier protein
-
N-terminal hexahistidine-tagged apo-H protein
-
wild-type and mutant His-tagged LipB proteins
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
gene lipM, complements a lipB-defective Escherichia coli mutant strain
-
for expression in Escherichia coli BL21DE3 pLysS cells
His-tagged LipB
-
N-terminal hexahistidine-tagged apo-H protein
-
wild-type and mutant His-tagged LipB proteins
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C150A
-
loss of the overall catalytic activity and an inability to form the acyl-enzyme intermediate
C150S
-
loss of the overall catalytic activity and an inability to form the acyl-enzyme intermediate
K165A
-
mutant has weakened catalytic ability
C137A/C169A
-
mutant protein retains trace activity
C169A
-
mutant enzyme retains trace activity, mutant enzyme forms an octanoyl-LpiB species that is not catalytically competent
C169S
-
mutant enzyme has no activity, mutant enzyme forms an octanoyl-LpiB species that is not catalytically competent
K165R
-
mutant remains active
additional information
-
construction of strain NM57 in which lipM is replaced with a kanamycin-resistance determinant. Gene lipM is placed under control of a xylose-inducible promoter PxylA is introduced into the DELTAlipM strain NM57 giving the lipM amyE::PxylA-lipM strain NM08. LipM can be functionally replaced by expression of Escherichia coli lipB, expression of Escherichia coli lipB allows growth of Bacillus subtilis DELTAlipL or DELATlipM strains in the absence of supplements. In contrast, growth of an Escherichia coli DELTAlipB strain can be complemented with lipM, but not lipL
C169S
-
the hydrolyzed C169S mutant protein shows higher methyl octanoate levels than those of the wild type protein preparations
additional information
-
Escherichia coli wild type strain and several spontaneous LipB knockout strains are used
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
enzyme is considerably upregulated in patients with multiple-drug-resistant Mycobacterium tuberculosis