Information on EC 2.5.1.72 - quinolinate synthase

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

EC NUMBER
COMMENTARY hide
2.5.1.72
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RECOMMENDED NAME
GeneOntology No.
quinolinate synthase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
NAD biosynthesis I (from aspartate)
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nicotine biosynthesis
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superpathway of nicotine biosynthesis
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NAD metabolism
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SYSTEMATIC NAME
IUBMB Comments
glycerone phosphate:iminosuccinate alkyltransferase (cyclizing)
An iron-sulfur protein that requires a [4Fe-4S] cluster for activity [1]. Quinolinate synthase catalyses the second step in the de novo biosynthesis of NAD+ from aspartate in some bacteria, with EC 1.4.3.16 (L-aspartate oxidase) catalysing the first step and EC 2.4.2.19 [nicotinate-nucleotide diphosphorylase (carboxylating)] the third step. In Escherichia coli, two of the residues that are involved in the [4Fe-4S] cluster binding appear to undergo reversible disulfide-bond formation that regulates the activity of the enzyme [5].
CAS REGISTRY NUMBER
COMMENTARY hide
39434-08-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isoform NadA
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
dihydroxyacetone phosphate + iminoaspartate
? + H2O + phosphate
show the reaction diagram
additional information
?
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residues C291 and C294 of the C291XXC294XXC297 motif undergo reversible disulfide formation, which regulates the activity of the enzyme
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4Fe-4S-center
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inhibitor 4,5-dithiohydroxyphthalic acid coordinates to the enzyme [4Fe-4S] cluster through a differentiated iron site
iron-sulfur centre
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4Fe-4S cluster
the enzyme requires a [4Fe4S] cluster for full activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
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inhibits reactivation of O2-inactivated enzyme
2,2'-dipyridyl
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inhibits reactivation of O2-inactivated enzyme
4,5-dithiohydroxyphthalic acid
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structural analogue of the 5-hydroxy-4,5-dihydropyridine-2,3-dicarboxylic acid intermediate. Compound coordinates to the enzyme [4Fe-4S] cluster through a differentiated iron site, thus leading to the inhibition of quinolate formation. Compound is inhibitory in vitro and in vivo
H2O2
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1 mM, inactivation
paraquat
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inactivation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.36
dihydroxyacetone phosphate
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25C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.007
4,5-dithiohydroxyphthalic acid
Escherichia coli
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pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.027
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25C, presence of oxygen to reoxidize NadB in the coupled assay
0.05
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25C, presence of fumarate as electron acceptor for NadB in the coupled assay
0.6
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pH 7.0, 25C
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
80000
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gel filtration, major amount of protein
124000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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plus minor amount of monomer. 2 * 40000, SDS-PAGE, 2 * 39300, calculated
monomer
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1 * 40000, SDS-PAGE, 1 * 39300, calculated
trimer
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3 * 41000, calculated
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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residues C291 and C294 of the C291XXC294XXC297 motif undergo reversible disulfide formation, which regulates the activity of the enzyme. Disulfide-bond formation and reduction are effected by oxidized and reduced forms of thioredoxin, with a midpoint potential of -264 mV for the redox couple
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
both native and SeMet enzyme are crystallized using the hanging-drop vapor-diffusion method at 22C, structure is determined at 2.8 A resolution
in presence of substrate analogue malate. Diffraction to 2.0 A resolution. Triangular architecture composed of a 3fold repeat of three-layer alphabetaalpha sandwich folding. The active site is located at the interface of the three domains and is centered on the pseudo-3fold axis. The malate molecule is tightly held near the bottom of the active site cavity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme, purification from inclusion bodies
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recombinant protein
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recombinant protein, complete loss of activity upon purification of enzyme in aerobic conditions or exposure to oxygen overnight
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli, N-terminal His-tag
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expression with C-terminal His-tag
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expression with N-terminal His-tag
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C110S
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0.4 mol iron per mol of protein, no enzymic activity
C230S
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0.6 mol iron per mol of protein, no enzymic activity
C259S
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4.5 mol iron per mol of protein, 80% of wild-type activity
C318S
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3.3 mol iron per mol of protein, 75% of wild-type activity
C318S/C320S
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0.3 mol iron per mol of protein, no enzymic activity
C320S
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1.5 mol iron per mol of protein, no enzymic activity
C82S
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4.3 mol iron per mol of protein, activity similar to wild-type
C113S
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1.3 iron ions per polypeptide, no catalytic activity
C119A
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2.9 mol of iron and sulfur per mol of protein
C119S
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1.0 iron ions per polypeptide
C128S
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2.7 iron ions per polypeptide
C195S
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1.5 iron ions per polypeptide
C200S
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1.0 iron ions per polypeptide, no catalytic activity
C291A
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3.9 mol of iron and sulfur per mol of protein
C291A/C294A
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3.7 mol of iron and sulfur per mol of protein
C291A/C294A/C297A
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0.5 mol of iron and sulfur per mol of protein
C291S
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0.8 iron ions per polypeptide
C294A
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3.2 mol of iron and sulfur per mol of protein
C294A/C297A
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0.6 mol of iron and sulfur per mol of protein
C294S
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2.1 iron ions per polypeptide
C297S
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0.3 iron ions per polypeptide, no catalytic activity
C64S
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1.4 iron ions per polypeptide
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
O2-dependent inactivation inactivation in extracts can be gradually reversed during anaerobic incubation, but is blocked by 2,2'-dipyridyl or by 1,10-phenanthroline
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis
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production of quinolinic acid from L-aspartate, dihydroxyacetone phosphate, and O2 by use of enzymes NadA and NadB
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