Any feedback?
Information on EC 2.5.1.72 - quinolinate synthase and Organism(s) Thermotoga maritima and UniProt Accession Q9X1X7
for references in articles please use BRENDA:EC2.5.1.72Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.5.1.72 quinolinate synthaseIUBMB 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 .
Specify your search results
Word Map
- 2.5.1.72
-
nada
- nicotinamide
- dihydroxyacetone
- iminoaspartate
-
iron-sulfur
-
pyrococcus
- dhap
- horikoshii
- qa
-
cluster-containing
-
oxygen-sensitive
-
desulfurase
- drug development
- synthesis
The taxonomic range for the selected organisms is: Thermotoga maritima
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
quinolinate synthase, quinolinate synthetase, sufe3, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
quinolinate synthetase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate
reaction mechanism with an early release of phosphate from dihydroxyacetone phosphate, that only, not glycerol 3-phosphate, can condense with iminoaspartate to form quinolinate. The NadA three-dimensional structure shows that there is no room in the active site to accommodate a condensation product on which the phosphate group from dihydroxyacetone phosphate is still present, overview. The enzyme has a triose phosphate isomerase activity catalyzing the reversible isomerization of glycerol 3-phosphate into dihydroxyacetone phosphate in an Fe/S-dependent manner
glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate
the presence of the Fe4S4 cluster generates an internal tunnel and a cavity to bind the substrate and and dehydrate it, which is initiated by the conserved residue Tyr21. Tyr21 is close to a conserved Thr-His-Glu. All of these residues are essential for activity and Tyr21 deprotonation, to form the reactive nucleophilic phenoxide anion, is mediated by the triad. NadA displays a dehydration mechanism significantly different from the one found in archetypical dehydratases such as aconitase, which use a serine residue deprotonated by an oxyanion hole
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -
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
39434-08-7
-
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
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
-
-
-
?
additional information
?
-
the enzyme has a triose phosphate isomerase activity catalyzing the reversible isomerization of glycerol 3-phosphate into dihydroxyacetone phosphate in an Fe/S-dependent manner. Only dihydroxyacetone phosphate can then condense with iminoaspartate to form quinolinate. If glycerol 3-phosphate is not converted to dihydroxyacetone phosphate no quinolinate can be produced. The enzyme as triose phosphate isomerase is more efficient in the direction of dihydroxyacetone phosphate production
-
-
?
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
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
[4Fe-4S] cluster
[4Fe-4S] cluster
an [4Fe-4S] cluster-containing enzyme. The Fe/S cluster of NadA (both Fe4S4 and Fe2S2) might play a significant structural role in NadA that could affect the triose phosphate isomerase activity
[4Fe-4S] cluster
the presence of the [4Fe-4S] cluster generates an internal tunnel and a cavity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Phosphoglycolic acid
significantly inhibits the enzyme's triose phosphate isomerase activity at 1 mM
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
quinolinate synthase is a Fe4S4 cluster-containing dehydrating enzyme involved in the synthesis of quinolinic acid, the universal precursor of the essential nicotinamide adenine dinucleotide coenzyme
physiological function
quinolinate synthase is an [4Fe-4S] cluster-containing dehydrating enzyme involved in synthesis of quinolinic acid, the universal precursor of the essential coenzyme nicotinamide adenine dinucleotide
PDB
SCOP
CATH
UNIPROT
ORGANISM
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant K219R/Y107F in complex with the first intermediate resulting from the condensation of dihydroxyacetone phosphate with iminoaspartate and the dihydroxyacetone phosphate analogue phosphoglycolohydroxamate, and mutant K219R/Y21F in complex with quinolinic acid. Phosphoglycolohydroxamate binds to NadA with its phosphate group at the site where the carboxylate groups of the first intermediate also bind
structures of complexes of the Y21F/K219R variant with 4-mercaptophthalic acid, 6-mercaptopyridine-2,3-dicarboxylic acid and 5-mercaptopyrazine-2,3-dicarboxylic acid, at 1.64 A, 1.9 A and 2.1 A resolution, respectively. The carboxylate groups of the inhibitors interact with active site amino acids of His19 and Ser36 (domain 1), Ser124 (domain 2) and His193 and Thr210 (domain 3), and all molecules bind to one iron of the cluster with their thiolate moiety
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K219R/Y107F
crystallization data. The mutated protein is unable to catalyze the aldo-keto isomerization and/or cyclization of the first intermediate resulting from the condensation of dihydroxyacetone phosphate with iminoaspartate that ultimately leads to quinolinic acid formation
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
te enzyme is required for the biosynthesis of NAD. Besides the de novo pathway for NAD synthesis, a salvage pathway exists in some organisms allowing NAD to be recycled from nicotinic acid and nicotinamide. Some pathogens such as Mycobacterium leprae and Helicobacter pylori lack this salvage pathway. The different pathways for quinolinate biosynthesis in most prokaryotes and eukaryotes, combined with the fact that the salvage pathway is absent in some pathogenic microorganisms, make enzyme NadA an ideal target in the search for specific antibacterial drugs
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Reichmann, D.; Coute, Y.; Ollagnier de Choudens, S.
Dual activity of quinolinate synthase: triose phosphate isomerase and dehydration activities play together to form quinolinate
Biochemistry
54
6443-6446
2015
Escherichia coli K-12 (P11458), Thermotoga maritima (Q9X1X7)
Cherrier, M.V.; Chan, A.; Darnault, C.; Reichmann, D.; Amara, P.; Ollagnier de Choudens, S.; Fontecilla-Camps, J.C.
The crystal structure of Fe4S4 quinolinate synthase unravels an enzymatic dehydration mechanism that uses tyrosine and a hydrolase-type triad
J. Am. Chem. Soc.
136
5253-5256
2014
Thermotoga maritima (Q9X1X7), Thermotoga maritima MSB8 / DSM 3109 / ATCC 43589 (Q9X1X7)
Saez Cabodevilla, J.; Volbeda, A.; Hamelin, O.; Latour, J.M.; Gigarel, O.; Clemancey, M.; Darnault, C.; Reichmann, D.; Amara, P.; Fontecilla-Camps, J.C.; Ollagnier de Choudens, S.
Design of specific inhibitors of quinolinate synthase based on [4Fe-4S] cluster coordination
Chem. Commun. (Camb.)
55
3725-3728
2019
Escherichia coli (P11458), Thermotoga maritima (Q9X1X7), Thermotoga maritima DSM 3109 (Q9X1X7), Escherichia coli K12 (P11458)
Volbeda, A.; Darnault, C.; Renoux, O.; Reichmann, D.; Amara, P.; Ollagnier de Choudens, S.; Fontecilla-Camps, J.C.
Crystal Structures of quinolinate synthase in complex with a substrate analogue, the condensation intermediate, and substrate-derived product
J. Am. Chem. Soc.
138
11802-11809
2016
Thermotoga maritima (Q9X1X7), Thermotoga maritima, Thermotoga maritima DSM 3109 (Q9X1X7)
EXTERNAL LINKS (specific for EC-Number 2.5.1.72)
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
