Any feedback?
Information on EC 2.3.1.12 - dihydrolipoyllysine-residue acetyltransferase and Organism(s) Geobacillus stearothermophilus and UniProt Accession P11961
for references in articles please use BRENDA:EC2.3.1.12Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.3.1.12 dihydrolipoyllysine-residue acetyltransferaseIUBMB Comments
A multimer (24-mer or 60-mer, depending on the source) of this enzyme forms the core of the pyruvate dehydrogenase multienzyme complex, and binds tightly both EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring) and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The lipoyl group of this enzyme is reductively acetylated by EC 1.2.4.1, and the only observed direction catalysed by EC 2.3.1.12 is that where the acetyl group is passed to coenzyme A.
Specify your search results
Word Map
- 2.3.1.12
-
lipoylated
-
multienzyme
- stearothermophilus
- thiamin
-
azotobacter
- vinelandii
-
subcomplexes
-
subunit-binding
-
lipoyl-lysine
-
e3-binding
-
icosahedral
- pdc-e2
-
1.2.4.1
-
lipoyl-bearing
-
dodecahedron
-
alpha2beta2
-
pentagonal
- e1alpha
-
e1beta
-
2-14cpyruvate
- molecular biology
- degradation
The taxonomic range for the selected organisms is: Geobacillus stearothermophilus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
dihydrolipoamide acetyltransferase, dihydrolipoyl transacetylase, lipoate acetyltransferase, dihydrolipoyl acetyltransferase, dhlta, dihydrolipoyl acetyl transferase, dihydrolipoyllysine-residue acetyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetyltransferase, lipoate
-
-
-
-
DHLTA
-
-
-
-
dihydrolipoate acetyltransferase
-
-
-
-
dihydrolipoic transacetylase
-
-
-
-
dihydrolipoyl acetyltransferase
E2
E2p
-
-
-
-
lipoate acetyltransferase
-
-
-
-
lipoate transacetylase
-
-
-
-
lipoic acetyltransferase
-
-
-
-
lipoic acid acetyltransferase
-
-
-
-
lipoic transacetylase
-
-
-
-
lipoylacetyltransferase
-
-
-
-
myelin-proteolipid O-palmitoyltransferase
-
-
-
-
palmitoyl-CoA:myelin-proteolipid O-palmitoyltransferase
-
-
-
-
thioltransacetylase A
-
-
-
-
transacetylase X
-
-
-
-
additional information
-
the enzyme forms the core unit E2 of the pyruvate dehydrogenase multienzyme complex binding the other components, i.e. pyruvate decarboxylase and dihydrolipoyl dehydrogenase, tightly at its peripheral domain
dihydrolipoyl acetyltransferase
-
-
-
-
E2
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + enzyme N6-(dihydrolipoyl)lysine = CoA + enzyme N6-(S-acetyldihydrolipoyl)lysine
reaction mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:enzyme N6-(dihydrolipoyl)lysine S-acetyltransferase
A multimer (24-mer or 60-mer, depending on the source) of this enzyme forms the core of the pyruvate dehydrogenase multienzyme complex, and binds tightly both EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring) and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The lipoyl group of this enzyme is reductively acetylated by EC 1.2.4.1, and the only observed direction catalysed by EC 2.3.1.12 is that where the acetyl group is passed to coenzyme A.
CAS REGISTRY NUMBER
COMMENTARY
9032-29-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
dihydrolipoamide + acetyl-CoA
S-acetyldihydrolipoamide + CoA
-
-
-
?
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.013
acetyl-CoA
-
catalytic domain after expression in Escherichia coli
1.2
dihydrolipoamide
-
catalytic domain after expression in Escherichia coli
additional information
additional information
-
the complex assembly and maintainance is regulated by thermodynamic homeostasis or entropy-enthalpy compensation
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
-
gel filtration in the presence of guanidinium hydrochloride
additional information
additional information
-
high molecular mass species in the absence of guanidinium hydrochloride
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
polymer
additional information
polymer
-
stoichiometry of pyruvate dehydrogenase complexes
additional information
cryoelectron microscopic analysis of the reconstructed three-dimensional structure of the purified E2E3 complex (dihydrolipoyl acetyltransferase/dihydrolipoyl dehydrogenase) and use of automated docking methods to interpret the density map in terms of the probable localization of the dihydrolipoyl acetyltransferase E2 and dihydrolipoyl dehydrogenase E3 molecules. The arrangement of pyruvate decarboxylase E1 and dihydrolipoyl dehydrogenase E3 molecules in the outer shell of the pyruvate dehydrogenase complex are remarkably similar and indicate that the design of the annular gap allows the lipoyl domain to have access to the active sites of pyruvate decarboxylase E1, dihydrolipoyl acetyltransferase E2, and dihydrolipoyl dehydrogenase E3 enzymes from within the annular gap
additional information
-
cryoelectron microscopic analysis of the reconstructed three-dimensional structure of the purified E2E3 complex (dihydrolipoyl acetyltransferase/dihydrolipoyl dehydrogenase) and use of automated docking methods to interpret the density map in terms of the probable localization of the dihydrolipoyl acetyltransferase E2 and dihydrolipoyl dehydrogenase E3 molecules. The arrangement of pyruvate decarboxylase E1 and dihydrolipoyl dehydrogenase E3 molecules in the outer shell of the pyruvate dehydrogenase complex are remarkably similar and indicate that the design of the annular gap allows the lipoyl domain to have access to the active sites of pyruvate decarboxylase E1, dihydrolipoyl acetyltransferase E2, and dihydrolipoyl dehydrogenase E3 enzymes from within the annular gap
additional information
-
the enzyme forms the core unit of the pyruvate dehydrogenase multienzyme complex binding the other components, i.e. pyruvate decarboxylase E1 and dihydrolipoyl dehydrogenase E3, tightly at its peripheral domain, Arg135 is important for interactions with E1 and E3, Met131 is involved in binding of E1, interaction analysis by surface plasmon resonance
additional information
-
distinct modes of recognition of the lipoyl domain of the dihydrolipoyl acetyltransferase (E2) component as substrate by the E1 and E3 components of the pyruvate dehydrogenase multienzyme complex
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
E3 dimer with E2 and a small binding domain E2BD, hanging drop vapor diffusion method
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K136A
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
K153A
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
M131A
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
R135A
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
R135C
-
site-directed mutagenesis, additional alkylation of the mutant enzymes with methyl, ethyl, propyl and butyl groups, the modifications cause alterations in interaction of core unit, E1 and E3 in the enzyme complex compared to the wild-type complex, thermodynamics and kinetics in comparison to the wild-type enzyme, overview
R135K
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
R135L
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
R135M
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
R139A
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
R146A
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
R156A
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
S133A
-
site-directed mutagenesis, thermodynamics and kinetics in comparison to the wild-type enzyme
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70
-
incubation converts core of the enzyme into an unidentified active molecular form X, loss of 10% enzyme activity after 5 h
78
-
temperatures below result in less than 5% loss in enzyme activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of truncated thrombin-cleavable enzyme in Escherichia coli strain BL21(DE3)
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
treatment with guanidine hydrochloride and its subsequent removal results in little recovery of the core, but full recovery of X
-
treatment with guanidine hydrochloride results in dissociation into subunits, removal of guanidine hydrochloride results in refolding of the enzyme with 95% of the original activity
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Reed, L.J.; Yeaman, S.J.
Pyruvate dehydrogenase
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
18
77-95
1987
Geobacillus stearothermophilus, Mammalia
-
Henderson, C.E.; Perham, R.N.
Purificaton of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus and resolution of its four component polypeptides
Biochem. J.
189
161-172
1980
Geobacillus stearothermophilus
Borges, A.; Hawkins, C.F.; Packman, L.C.; Perham, R.N.
Cloning and sequence analysis of the genes encoding the dihydrolipoamide acetyltransferase and dihydrolipoamide dehydrogenase components of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus
Eur. J. Biochem.
194
95-102
1990
Geobacillus stearothermophilus
Dardel, F.; Packman, L.C.; Perham, R.N.
Expression in Escherichia coli of a sub-gene encoding the lipoyl domain of the pyruvate dehydrogenase complex of Bacillus stearothermophilus [published erratum appears in FEBS Lett 1990 Jul 30;268(1):306]
FEBS Lett.
264
206-210
1990
Geobacillus stearothermophilus
Packman, L.C.; Borges, A.; Perham, R.N.
Amino acid sequence analysis of the lipoyl and peripheral subunit-binding domains in the lipoate acetyltransferase component of the pyruvate dehydrogenase complex from Bacillus stearothermophilus
Biochem. J.
252
79-86
1988
Geobacillus stearothermophilus
Allen, M.D.; Perham, R.N.
The catalytic domain of dihydrolipoyl acetyltransferase from the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. Expression, purification and reversible denaturation
FEBS Lett.
413
339-343
1997
Geobacillus stearothermophilus
Aso, Y.; Nakajima, A.; Meno, K.; Ishiguro, M.
Thermally induced changes of lipoate acetyltransferase inner core isolated from the Bacillus stearothermophilus pyruvate dehydrogenase complex
Biosci. Biotechnol. Biochem.
65
698-701
2001
Geobacillus stearothermophilus
Mande, S.S.; Sarfaty, S.; Allen, M.D.; Perham, R.N.; Hol, W.G.J.
Protein-protein interactions in the pyruvate dehydrogenase multienzyme complex: dihydrolipoamide dehydrogenase complexed with the binding domain of dihydrolipoamide acetyltransferase
Structure
4
277-286
1996
Geobacillus stearothermophilus
Jung, H.I.; Cooper, A.; Perham, R.N.
Interactions of the peripheral subunit-binding domain of the dihydrolipoyl acetyltransferase component in the assembly of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus
Eur. J. Biochem.
270
4488-4496
2003
Geobacillus stearothermophilus
Allen, M.D.; Broadhurst, R.W.; Solomon, R.G.; Perham, R.N.
Interaction of the E2 and E3 components of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. Use of a truncated protein domain in NMR spectroscopy
FEBS J.
272
259-268
2005
Geobacillus stearothermophilus (P11961), Geobacillus stearothermophilus
Milne, J.L.; Wu, X.; Borgnia, M.J.; Lengyel, J.S.; Brooks, B.R.; Shi, D.; Perham, R.N.; Subramaniam, S.
Molecular structure of a 9-MDa icosahedral pyruvate dehydrogenase subcomplex containing the E2 and E3 enzymes using cryoelectron microscopy
J. Biol. Chem.
281
4364-4370
2006
Geobacillus stearothermophilus (P11961), Geobacillus stearothermophilus
EXTERNAL LINKS (specific for EC-Number 2.3.1.12)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
