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Information on EC 2.3.3.14 - homocitrate synthase and Organism(s) Schizosaccharomyces pombe and UniProt Accession Q9Y823

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EC Tree
     2 Transferases
         2.3 Acyltransferases
             2.3.3 Acyl groups converted into alkyl groups on transfer
                2.3.3.14 homocitrate synthase
IUBMB Comments
Belongs in the alpha-aminoadipate pathway of lysine synthesis, along with EC 4.2.1.36, homoaconitate hydratase. The enzyme also acts with oxaloacetate as substrate, but more slowly [2,3].
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Schizosaccharomyces pombe
UNIPROT: Q9Y823
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Word Map
  • 2.3.3.14
  • gyrus
  • resting-state
  • frontal
  • deficit
  • sclerosis
  • cingulate
  • schizophrenia
  • hair
  • emotional
  • prefrontal
  • inferior
  • anxiety
  • bipolar
  • neuropsychological
  • auditory
  • parietal
  • insula
  • neuroimaging
  • occipital
  • default
  • precuneus
  • high-content
  • verbal
  • cochlea
  • putamen
  • whole-brain
  • tensor
  • voxel-based
  • precentral
  • nervosa
  • first-episode
  • relapsing-remitting
  • obsessive-compulsive
  • salience
  • hemichannels
  • t1-weighted
  • orbitofrontal
  • dlpfc
  • visuospatial
  • unmedicated
  • parahippocampal
  • impulsivity
  • event-related
  • fluency
  • fasciculus
  • connectome
  • tractography
  • peripapillary
  • euthymic
  • stroop
  • biotechnology
  • synthesis
  • medicine
The taxonomic range for the selected organisms is: Schizosaccharomyces pombe
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
hcs, homocitrate synthase, lys22, nifv2, sphcs, tthcs, lys21p, homocitrate synthetase, lys22p, saci_1304, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homocitrate synthase
-
2-hydroxybutane-1,2,4-tricarboxylate 2-oxoglutarate-lyase (CoA-acetylating)
-
-
-
-
acetyl-coenzyme A:2-ketoglutarate C-acetyl transferase
-
-
-
-
homocitrate synthase
-
-
homocitrate synthetase
-
-
-
-
homocitrate-condensing enzyme
-
-
-
-
homocondensing enzyme
-
-
-
-
synthase, homocitrate
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
aldol condensation
-
condensation
-
-
-
-
aldol condensation
-
-
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:2-oxoglutarate C-acetyltransferase (thioester-hydrolysing, carboxymethyl forming)
Belongs in the alpha-aminoadipate pathway of lysine synthesis, along with EC 4.2.1.36, homoaconitate hydratase. The enzyme also acts with oxaloacetate as substrate, but more slowly [2,3].
CAS REGISTRY NUMBER
COMMENTARY hide
9075-60-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + H2O + 2-oxoglutarate
(R)-2-hydroxybutane-1,2,4-tricarboxylate + CoA
show the reaction diagram
-
-
-
?
acetyl-CoA + H2O + 2-oxoglutarate
(R)-2-hydroxybutane-1,2,4-tricarboxylate + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + H2O + 2-oxoglutarate
2-hydroxybutane-1,2,4-tricarboxylate + CoA
show the reaction diagram
additional information
?
-
-
homocitrate synthase is a labile target for oxidative stress caused by CuZn-superoxide dismutase depletion
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + H2O + 2-oxoglutarate
(R)-2-hydroxybutane-1,2,4-tricarboxylate + CoA
show the reaction diagram
-
-
-
?
acetyl-CoA + H2O + 2-oxoglutarate
(R)-2-hydroxybutane-1,2,4-tricarboxylate + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + H2O + 2-oxoglutarate
2-hydroxybutane-1,2,4-tricarboxylate + CoA
show the reaction diagram
-
first enzyme of the lysine biosynthetic pathway
-
-
?
additional information
?
-
-
homocitrate synthase is a labile target for oxidative stress caused by CuZn-superoxide dismutase depletion
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-lysine
feedback inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.159 - 9.66
2-oxoglutarate
0.0107 - 0.0477
acetyl-CoA
0.159 - 24.4
2-oxoglutarate
0.006 - 0.146
acetyl-CoA
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.75 - 5.133
2-oxoglutarate
2.833 - 4.983
acetyl-CoA
0.2 - 5.13
2-oxoglutarate
0.18 - 4.98
acetyl-CoA
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
activity assay
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
activity assay at room temperature
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
reaction is the first step in the lysine biosynthetic pathway through alpha-aminoadipate
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
the structure of SpHCS in complex with the inhibitor L-lysine and Zn2+ is solved at a resolution of 2.38 A
the crystal structure of the homocitrate synthase apoenzyme and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate are reported
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E167A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
E167Q
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
E74A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
E74Q
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
H103A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
Q47A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
R163A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
R163K
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
R163Q
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
R43A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
R43K
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
R43Q
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
S165A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
T197A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
T197S
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
T197V
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
Y332A
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
Y332F
-
mutant, reveals the contribution of this residue to substrate binding and catalysis
additional information
-
activity and protein level of homocitrate synthase are dramatically reduced upon depletion of CuZn-superoxide dismutase. Overexpression of the lys4 gene increases homocitrate synthase activity and is sufficient to suppress the lysine requirement of CuZn-superoxide dismutase-deficient cells
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
on Talon or Zn2+ charged IMAC sepharose resin
on a Talon Co2+ immobilized metal affinity chromatography column or a Zn2+ charged IMAC sepharose column
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
into the parallel expression vector pHIS2
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
homocitrate synthase is a potential target for antifungal drugs
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ye, Z.H.; Bhattacharjee, J.K.
Lysine biosynthesis pathway and biochemical blocks of lysine auxotrophs of Schizosaccharomyces pombe
J. Bacteriol.
170
5968-5970
1988
Schizosaccharomyces pombe
Manually annotated by BRENDA team
Kwon, E.S.; Jeong, J.H.; Roe, J.H.
Inactivation of homocitrate synthase causes lysine auxotrophy in copper/zinc-containing superoxide dismutase-deficient yeast Schizosaccharomyces pombe
J. Biol. Chem.
281
1345-1351
2006
Schizosaccharomyces pombe
Manually annotated by BRENDA team
Bulfer, S.L.; Scott, E.M.; Couture, J.F.; Pillus, L.; Trievel, R.C.
Crystal structure and functional analysis of homocitrate synthase, an essential enzyme in lysine biosynthesis
J. Biol. Chem.
284
35769-35780
2009
Schizosaccharomyces pombe
Manually annotated by BRENDA team
Bulfer, S.L.; Scott, E.M.; Pillus, L.; Trievel, R.C.
Structural basis for L-lysine feedback inhibition of homocitrate synthase
J. Biol. Chem.
285
10446-10453
2010
Schizosaccharomyces pombe (Q9Y823), Schizosaccharomyces pombe
Manually annotated by BRENDA team