Information on EC 2.3.1.117 - 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase

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The expected taxonomic range for this enzyme is: Bacteria

EC NUMBER
COMMENTARY
2.3.1.117
-
RECOMMENDED NAME
GeneOntology No.
2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
succinyl-CoA + (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + H2O = CoA + N-succinyl-L-2-amino-6-oxoheptanedioate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Lysine biosynthesis
-
lysine biosynthesis I
-
Metabolic pathways
-
Microbial metabolism in diverse environments
-
SYSTEMATIC NAME
IUBMB Comments
succinyl-CoA:(S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase
Involved in the biosynthesis of lysine in bacteria (including cyanobacteria) and higher plants. The 1992 edition of the Enzyme List erroneously gave the name 2,3,4,5-tetrahydropyridine-2-carboxylate N-succinyltransferase to this enzyme.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mtb-DapD
O05302
in complex with cofactor succinyl-CoA
succinyl-CoA:tetrahydrodipicolinate N-succinyltransferase
-
-
-
-
succinyltransferase, tetrahydrodipicolinate
-
-
-
-
tetrahydrodipicolinate N-succinyltransferase
-
-
-
-
tetrahydrodipicolinate N-succinyltransferase
O05302
-
tetrahydrodipicolinate N-succinyltransferase
-
-
tetrahydrodipicolinate succinylase
-
-
-
-
tetrahydrodipicolinate succinyltransferase
-
-
-
-
tetrahydrodipicolinate-N-succinyltransferase
Q8X8Y7
-
tetrahydrodipicolinate-N-succinyltransferase
-
-
THDP
Q8X8Y7
-
CAS REGISTRY NUMBER
COMMENTARY
88086-34-4
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
enzyme is a member of the hexapeptide acyltransferase superfamily
-
-
Manually annotated by BRENDA team
strain BCG
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
the DAP biosynthesis pathway is present in most Gram-negative bacteria and mycobacteria
metabolism
-
tetrahydrodipicolinate N-succinyltransferase catalyses the transfer of the succinyl moiety of succinyl-CoA to the alpha-amino group of tetrahydrodipicolinate, the first committed step in the succinylase branch of the DAP biosynthesis pathway, diaminopimelic acid pathway of lysine biosynthesis, overview
physiological function
-, O05302
part of L-lysine biosynthetic pathway
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
-
-
-
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
-
-
?
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
-
-
-
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
-
-
?
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
-
-
?
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
product formation is strongly preferred
-
r
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
involved in the four-step succinylase branch of the L-lysine biosynthetic pathway
-
?
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
involved in the biosynthesis of lysine in bacteria, blue-green algae and higher plants
-
-
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
involved in the biosynthesis of lysine in bacteria, blue-green algae and higher plants
-
r
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
involved in the biosynthesis of lysine in bacteria, blue-green algae and higher plants
-
-
succinyl-CoA + (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + H2O
CoA + N-succinyl-L-2-amino-6-oxoheptanedioate
show the reaction diagram
-
the enzyme is absolutely specific for the L-2-aminopimelate enantiomer, the enzyme is absolutely specific for the L-2-aminopimelate enantiomer, L-2-aminopimelate and weak inhibitor D-2-aminopimelate bind at the same site of the enzyme. Binding interaction analysis of the ligands in the enzyme active site suggests a misalignment of the amino group of D-2-aminopimelate for nucleophilic attack on the succinate moiety of the co-substrate succinyl-CoA as the structural basis of specificity and inhibition
-
-
?
succinyl-CoA + 3,4-dihydro-2H-1,4-thiazine-3,5-dicarboxylic acid
?
show the reaction diagram
-
-
-
-
?
succinyl-CoA + 6-amino-2-hydroxypimelic acid
CoA + N-succinyl-6-amino-2-hydroxypimelate
show the reaction diagram
-
-
-
?
succinyl-CoA + L-2-aminopimelate
CoA + N-succinyl-L-aminopimelate
show the reaction diagram
-, Q8X8Y7
-
-
-
?
succinyl-CoA + L-2-aminopimelate
CoA + N-succinyl-L-aminopimelate
show the reaction diagram
-
tetrahydrodipicolinate analogue
-
?
succinyl-CoA + L-6-amino-L-2-hydroxypimelic acid
CoA + N-succinyl-L-6-amino-L-2-hydroxypimelate
show the reaction diagram
-
mixture of isomers
-
?
succinyl-CoA + tetrahydrodipicolinate
?
show the reaction diagram
-
-
-
-
-
succinyl-CoA + tetrahydrodipicolinate
?
show the reaction diagram
-, Q8X8Y7
-
-
-
?
additional information
?
-
-
no activity ith L-lysine, adipic acid, alpha-amino-adipic acid, L-epsilon-acetyl-lysine, L-glutamate, L-glutamine, L-norleucine, substrate specificity for DapD, overview. Binding of CoA to PaDapD does not induce any large conformational changes, ternary complex structure of DapD with bound CoA and succinate, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
-
-
-
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
-
-
?
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
-
-
?
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
involved in the four-step succinylase branch of the L-lysine biosynthetic pathway
-
?
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
involved in the biosynthesis of lysine in bacteria, blue-green algae and higher plants
-
-
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
involved in the biosynthesis of lysine in bacteria, blue-green algae and higher plants
-
r
succinyl-CoA + (2S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylic acid
CoA + (2S)-2-[(3-carboxypropanoyl)amino]-6-oxoheptanedioic acid
show the reaction diagram
-
involved in the biosynthesis of lysine in bacteria, blue-green algae and higher plants
-
-
succinyl-CoA + (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + H2O
CoA + N-succinyl-L-2-amino-6-oxoheptanedioate
show the reaction diagram
-
the enzyme is absolutely specific for the L-2-aminopimelate enantiomer
-
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-, O05302
slight increase of enzyme activity
Mg2+
-, O05302
stabilizes quartenary enzyme structure, slight increase of enzyme activity
Mn2+
-, O05302
slight increase of enzyme activity
Na+
-, O05302
stabilizes quartenary enzyme structure
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2,6-dihydroxypimelic acid
-
0.54 mM, 66% inhibition
2-Hydroxytetrahydropyran-2,6-dicarboxylic acid
-
competitive inhibition
2-oxopimelic acid
-
5 mM, 57% inhibition
4-oxo-(2E,5E)-heptadien-1,7-dioic acid
-
0.5 mM, 32% inhibition
6-Aminocaproic acid
-
5 mM, 35% inhibition
acetate
-, O05302
caused by inhibition of succinyl-CoA-binding or pH effect
CaCl2
-
1 mM, 3% inhibition
Co2+
-, O05302
partial inhibition
CoCl2
-
1 mM, 95% inhibition
CuSO4
-
1 mM, complete loss of activity
D-2-aminopimelate
-
competitive vs. L-2-aminopimelate and tetrahydropicolinate
D-2-aminopimelate
-
very weak competitive inhibition, L-2-aminopimelate and D-2-aminopimelate bind at the same site of the enzyme. Binding interaction analysis of the ligands in the enzyme active site suggests a misalignment of the amino group of D-2-aminopimelate for nucleophilic attack on the succinate moiety of the co-substrate succinyl-CoA as the structural basis of specificity and inhibition
D-2-hydroxypimelic acid
-
5 mM, 93% inhibition
DL-2-amino-5-thiapimelic acid
-
5 mM, 75% inhibition
L-2-hydroxypimelic acid
-
5 mM, 88% inhibition
MgCl2
-
1 mM, 20% inhibition
N-ethylmaleimide
-
16 mM, 42% inhibition
p-Chloromercuriphenylsulfonate
-
0.16 mM, 97% inhibition
pimelic acid
-
5 mM, 43% inhibition
Zn2+
-, O05302
1 mM, complete loss of enzyme acitivity
ZnCl2
-
1 mM, 88% inhibition
MnCl2
-
1 mM, 9% inhibition
additional information
-
not inhibited by EDTA and Fe2+
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
7
-
(S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate
-
pH 7.5, 22C
2
-
3,4-dihydro-2H-1,4-thiazine-3,5-dicarboxylic acid
-
-
0.015
-
succinyl-CoA
-
-
0.02
-
tetrahydrodipicolinate
-
-
0.022
-
tetrahydrodipicolinate
-
-
1
-
L-2-aminopimelate
-
-
additional information
-
additional information
-
reaction kinetics for DapD, overview
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5.8e-05
-
2-Hydroxytetrahydropyran-2,6-dicarboxylic acid
-
-
0.31
-
D-2-aminopimelate
-
vs. L-2-aminopimelate
0.76
-
D-2-aminopimelate
-
vs. tetrahydropicolinate
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
20
-
D-2-aminopimelate
-
pH 7.5, 22C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.5
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
9
-
50% of maximal activity at pH 7, 75% of maximal activity at pH 9.0
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
assay at
37
-
-
assay at
PDB
SCOP
CATH
ORGANISM
Brucella suis biovar 1 (strain 1330)
Burkholderia pseudomallei (strain 1710b)
Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Unknown prokaryotic organism
Unknown prokaryotic organism
Unknown prokaryotic organism
Unknown prokaryotic organism
Unknown prokaryotic organism
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
68000
-
-
gel filtration
72000
-
-
sucrose density gradient centrifugation
100000
-
-
gel filtration, homotrimer
110000
-
-
recombinant DapD, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
2 * 31000, SDS-PAGE
homotrimer
-
gel filtration
trimer
-
the subunit of PaDapD consists of three domains, the N-terminal globular domain, a central domain, and a C-terminal domain, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structure of DapD from Escherichia coli at 2.0 A resolution is shown. Comparison of the structure with the homologous enzyme from Mycobacterium bovis reveals the C-terminal helix undergoes a large rearrangement upon substrate binding, which contributes to cooperativity in substrate binding
-, Q8X8Y7
crystal structure in complex with L-2-aminopimelate/coenzyme A and L-2-amino-6-oxopimelate/coenzyme A at 2.0 A resolution, hanging drop vapor diffusion from solutions of 10-13% poly(ethylene glycol) 4000, 94 mM MES, pH 6.4, 94 mM ammonium sulfate, and 4.7% 2-propanol in the presence of 16 mM (D,L)-2-aminopimelate and 2.5 mM CoA
-
crystal structure of the enzyme in ternary complexes with pimelate/succinyl-CoA and L-2-aminopimelate with the nonreactive cofactor analog succinamide-CoA, 2.3 and 2.0 A resolution, crystals are prepared by cocrystallization using the hanging drop vapor diffusion method, drops are formed by mixing 0.005 ml 27 mg/ml enzyme with an equal volume of 17% poly(ethylene glycol) 4000, 188 mM ammonium sulfate, 94 mM MES, pH 6.4, 4.7% 2-propanol, 20 mM pimelate, and 5 mM succinyl-CoA or 5 mM succinamide-CoA
-
crystallized from solutions of 16% poly(ethylene glycol) 4000, 200 mM ammonium sulfate, 100 mM HEPES, pH 7.5, and 10% 2-propanol, crystals belong to space group P21, X-ray structure refined to 2.2 A resolution
-
crystallized in the cubic space group I23 or I213. Diffraction data analysis indicates the presence of five molecules per asymmetric unit. Data exhibit icosahedral point-group symmetry. Enzyme might assembles into a 60-mer exhibiting 235 point-group symmetry and crystallizes as such in space group I23. In this case, the combination of crystallographic and noncrystallographic symmetry elements results in an arrangement of the icosahedrons in the cubic crystal with one pentamer in the asymmetric unit. Another explanation is that the packing of the molecules itself mimics icosahedral symmetry. In this case both space groups I23 and I213 would be possible
-
purified recombinant His6-tagged DapD with bound L-2-aminopimelate and D-2-aminopimelate or in complex with CoA/succinate, hanging drop vapour diffusion method, mixing of 0.002 ml of 26 mg/ml protein in 25 mM Tris-HCl pH 8.0, and 150 mM NaCl, with or without 10-15 mM CoA, with 0.002 ml of reservoir solution containing 19-20% of PEG3350, 0.3-0.4 M succinate, pH 6.2, and equilibration against reservoir solution for 1-2 days, incubation of the enzyme with formyl-CoA leads to better crystals, soaking of apoenzyme crystals in solution containing L-2-aminopimelate and D-2-aminopimelate, the CoA-complex also contains a succinatemolecule bound next to the acceptor arm of the CoA in the active site cleft, X-ray diffraction structure determination and analysis at 1.8-2.95 A resolution, molecular replacement
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purification has to be carried out at 0-4C
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, 0.001 M 2-mercaptoethanol, 80% remaining activity after 1 month
-
4C, no 2-mercaptoethanol, 4 days, 80% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
MnCl2, ammonium sulfate, DEAE-cellulose, acid treatment, hydroxyapatite, phenyl-Sepharose, chromatofocusing
-
using Ni-NTA chromatography
-, Q8X8Y7
recombinant enzyme
-
affinity and size-exclusion chromatography
-, O05302
using affinity chromatography and gel filtration
-
recombinant His-tagged DapD from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, removal of te the N-terminal His6-tag by thrombin cleavage is not successful
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli as a His-tagged fusion protein
-, Q8X8Y7
overexpressed in Escherichia coli
-
expressed in Escherichia coli
-
expression in Escherichia coli
-, O05302
gene dapD, phylogenetic tree, expression of His-tagged DapD in Escherichia coli strain BL21(DE3)
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E199A
-, O05302
completely inactive mutant
G222P
-, O05302
completely inactive mutant
additional information
-, O05302
binary complex of Mtb-DapD and succinyl-CoA
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
DapA is not an optimal target for drug development against Pseudomonas aeruginosa