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Information on EC 2.5.1.72 - quinolinate synthase and Organism(s) Pyrococcus horikoshii and UniProt Accession O57767

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EC Tree
IUBMB Comments
An iron-sulfur protein that requires a [4Fe-4S] cluster for activity . 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 .
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Pyrococcus horikoshii
UNIPROT: O57767
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Word Map
The taxonomic range for the selected organisms is: Pyrococcus horikoshii
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
quinolinate synthase, quinolinate synthetase, sufe3, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
quinolinate synthetase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate
show the reaction diagram
model of the catalytic state. Elimination of phosphate from dihydroxyacetone phosphate may precede the condensation reaction
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -
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
-
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
-
-
-
-
?
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
show the reaction diagram
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
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
[4Fe-4S]-center
substrate dihydroxyacetone phosphate chelates the cluster
iron-sulfur centre
-
protein contains a [4Fe-4S] cluster absolutely required for activity
[4Fe-4S]-center
-
NadA contains a [4Fe-4S] cluster cofactor with a unique, non-cysteinyl-ligated, iron ion (Fea), which binds the hydroxyl group of a postulated intermediate in the last step of the reaction to facilitate a dehydration. N1 and the C7 carboxylate group of quinolinate ligate to Fea in a bidentate fashion placing the C5 hydroxyl group of the postulated final intermediate distal to Fea and virtually incapable of coordinating to it
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
-
an [4Fe-4S] cluster-containing enzyme
Iron
-
protein contains a [4Fe-4S] cluster absolutely required for activity
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
quinolinate synthase is involved in synthesis of quinolinic acid, the universal precursor of the essential coenzyme nicotinamide adenine dinucleotide
additional information
-
three strictly conserved amino acids, Glu198, Tyr109, and Tyr23, are in close proximity to the bound product. Substitution of these amino acids with Gln, Phe, and Phe, respectively, leads to complete loss of activity
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
structures of NadA in complex with dihydroxyacetone phosphate, iminoaspartate analogues, and quinolinate. Dihydroxyacetone phosphate adopts a nearly planar conformation and chelates the [4Fe-4S] cluster via its keto and hydroxyl groups. The cluster may act as a Lewis acid in enediolate formation, like zinc in class II aldolases
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E198Q
-
site-directed mutagenesis, inactive mutant
Y109F
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site-directed mutagenesis, inactive mutant
Y23F
-
site-directed mutagenesis, inactive mutant
additional information
-
three strictly conserved amino acids, Glu198, Tyr109, and Tyr23, are in close proximity to the bound product. Substitution of these amino acids with Gln, Phe, and Phe, respectively, leads to complete loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Saunders, A.H.; Griffiths, A.E.; Lee, K.H.; Cicchillo, R.M.; Tu, L.; Stromberg, J.A.; Krebs, C.; Booker, S.J.
Characterization of quinolinate synthases from Escherichia coli, Mycobacterium tuberculosis, and Pyrococcus horikoshii indicates that [4Fe-4S] clusters are common cofactors throughout this class of enzymes
Biochemistry
47
10999-11012
2008
Escherichia coli, Mycobacterium tuberculosis, Pyrococcus horikoshii
Manually annotated by BRENDA team
Sakuraba, H.; Tsuge, H.; Yoneda, K.; Katunuma, N.; Ohshima, T.
Crystal structure of the NAD biosynthetic enzyme quinolinate synthase
J. Biol. Chem.
280
26645-26648
2005
Pyrococcus horikoshii (O57767), Pyrococcus horikoshii
Manually annotated by BRENDA team
Esakova, O.A.; Silakov, A.; Grove, T.L.; Saunders, A.H.; McLaughlin, M.I.; Yennawar, N.H.; Booker, S.J.
Structure of quinolinate synthase from Pyrococcus horikoshii in the presence of its product, quinolinic acid
J. Am. Chem. Soc.
138
7224-7227
2016
Pyrococcus horikoshii
Manually annotated by BRENDA team
Fenwick, M.K.; Ealick, S.E.
Crystal structures of the iron-sulfur cluster-dependent quinolinate synthase in complex with dihydroxyacetone phosphate, iminoaspartate analogues, and quinolinate
Biochemistry
55
4135-4139
2016
Pyrococcus horikoshii (O57767), Pyrococcus horikoshii, Pyrococcus horikoshii DSM 12428 (O57767)
Manually annotated by BRENDA team