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glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate
glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate
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glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate
model of the catalytic state. Elimination of phosphate from dihydroxyacetone phosphate may precede the condensation reaction
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
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
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
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dihydroxyacetone phosphate + iminoaspartate
? + H2O + phosphate
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
additional information
?
-
dihydroxyacetone phosphate + iminoaspartate
? + H2O + phosphate
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-
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?
dihydroxyacetone phosphate + iminoaspartate
? + H2O + phosphate
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-
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?
dihydroxyacetone phosphate + iminoaspartate
? + H2O + phosphate
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-
-
-
?
dihydroxyacetone phosphate + iminoaspartate
? + H2O + phosphate
-
-
-
-
?
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
-
-
-
?
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
-
-
-
-
?
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
-
condensation of dihydroxyacetone phosphate (DHAP) and aspartate-enamine by the action of quinolinate synthase, NadA
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?
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
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-
-
?
glycerone phosphate + iminosuccinate
pyridine-2,3-dicarboxylate + 2 H2O + phosphate
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-
?
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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?
additional information
?
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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
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?
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
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?
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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
E198Q
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site-directed mutagenesis, inactive mutant
Y109F
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site-directed mutagenesis, inactive mutant
Y23F
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site-directed mutagenesis, inactive mutant
K219R
mutant is able to bind citrate
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
K219R/Y21F
crystallization data
Y21F
mutant is able to bind citrate
Y21F/K219R
crystallization data with inhibitors
K219R
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mutant is able to bind citrate
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K219R/Y107F
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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
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K219R/Y21F
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crystallization data
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Y21F
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mutant is able to bind citrate
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Y21F/K219R
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crystallization data with inhibitors
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C113A
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0.8 iron ions per polypeptide, no catalytic activity
C113A
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1 mol of iron and sulfur per mol of protein, oligomer formation
C200A
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0.9 mol of iron and sulfur per mol of protein, oligomer formation
C200A
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1.5 iron ions per polypeptide, no catalytic activity
C297A
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0.3 iron ions per polypeptide, no catalytic activity
C297A
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0.4 mol of iron and sulfur per mol of protein, oligomer formation
additional information
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functional complementation of a corresponding Escherichia coli mutant. Gene disruption in Arabidospis thaliana is embryo-lethal
additional information
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knock-out of SufE3 is embryo-lethal
additional information
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the old5 lesion does not affect quinolinate synthase activity but decreases the protein's cysteine desulfurase activity resulting in increased NAD steady state levels concomitant with increased activity of enzymes in the NAD salvage pathway
additional information
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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
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Early steps in the biosynthesis of NAD in Arabidopsis start with aspartate and occur in the plastid
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851-857
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Quinolinate synthetase: the oxygen-sensitive site of de novo NAD(P)+ biosynthesis
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47
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Escherichia coli quinolinate synthetase does indeed harbor a [4Fe-4S] cluster
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127
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2005
Escherichia coli
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Crystal structure of the NAD biosynthetic enzyme quinolinate synthase
J. Biol. Chem.
280
26645-26648
2005
Pyrococcus horikoshii (O57767), Pyrococcus horikoshii
brenda
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282
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20
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Arabidopsis thaliana
brenda
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Gene nadA, encoding quinolinate synthetase, is located on the cyanelle DNA from Cyanophora paradoxa
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Cloning, overexpression, and purification of Escherichia coli quinolinate synthetase
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18
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