4.3.3.7: 4-hydroxy-tetrahydrodipicolinate synthase
This is an abbreviated version!
For detailed information about 4-hydroxy-tetrahydrodipicolinate synthase, go to the full flat file.
Word Map on EC 4.3.3.7
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4.3.3.7
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diaminopimelate
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4.2.1.52
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s-lysine
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drug development
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homoserine
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meso-diaminopimelate
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aspartokinase
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l-threonine
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s-aspartate
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s-2-aminoethyl-l-cysteine
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feedback-insensitive
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lysine-insensitive
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beta-semialdehyde
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pharmacology
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l-aspartate-beta-semialdehyde
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2.7.2.4
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aspartate-derived
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medicine
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synthesis
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agriculture
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biotechnology
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industry
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food industry
- 4.3.3.7
- diaminopimelate
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4.2.1.52
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s-lysine
- drug development
- homoserine
- meso-diaminopimelate
- aspartokinase
- l-threonine
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s-aspartate
- s-2-aminoethyl-l-cysteine
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feedback-insensitive
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lysine-insensitive
- beta-semialdehyde
- pharmacology
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l-aspartate-beta-semialdehyde
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2.7.2.4
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aspartate-derived
- medicine
- synthesis
- agriculture
- biotechnology
- industry
- food industry
Reaction
Synonyms
Aq_1143, AT2G45440, BA3935 gene product, cDHDPS, CjDHDPS, DapA, DapA2, DHDPA synthase, DHDPS, DHDPS2, dihydro-dipicolinic acid synthase, dihydrodipicolinate synthase, dihydrodipicolinic acid synthase, dihydrodipocolinate synthase, dihydropicolinate synthetase, EC 4.2.1.52, FaDHDPS, HTPA synthase, More, MosA, MosA protein, MRSA-DHDPS, PA1010, pyruvate-aspartic semialdehyde condensing enzyme, Rv2753c, synthase, dihydrodipicolinate, VEG81, Vegetative protein 81
ECTree
Advanced search results
Engineering
Engineering on EC 4.3.3.7 - 4-hydroxy-tetrahydrodipicolinate synthase
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L170E/G191E
K68H
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
P61A/T63L
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
P61A/T63L/A65H
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
T63L
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
T92E
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
T96E
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site-directed mutagenesis, the mutant is not inhibited by L-lysine and shows reduced activity compared to the wild-type enzyme
T96E/K68H
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site-directed mutagenesis, the mutant is not inhibited by L-lysine and shows reduced activity compared to the wild-type enzyme
T96E/K68H/P61A/T63L
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site-directed mutagenesis, the mutant is activated by L-lysine 3fold shows reduced activity compared to the wild-type enzyme
T96E/K68H/P61A/T63L/A65H
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site-directed mutagenesis the mutant is activated by L-lysine 5fold shows reduced activity compared to the wild-type enzyme
T96E/K68H/T63L
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site-directed mutagenesis, the mutant is activated by L-lysine and shows reduced activity compared to the wild-type enzyme
K68H
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
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P61A/T63L
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
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T63L
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
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T92E
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site-directed mutagenesis, the mutant is not inhibited by L-lysine
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A49K
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site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
A49P
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site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme and is still sensitive to L-lysine
A49W
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site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
D193Y
removal of water mediated hydrogen-bond network and introduction of steric bulk to alter surface topology
E84T
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site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme and is insensitive to L-lysine
H118Y
mutant enzyme H56K is more conducive to L-lysine production than mutant H118Y
H56K
K161A
K161R
catalytically active, significant decrease in activity. Is not inactivated when incubated with pyruvate and the reducing agent sodium borohydride. Negligible heat production associated with pyruvate binding to the mutant enzyme, consistent with the lack of Schiff base formation
L197D/Y107W
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site-directed mutagenesis, the mutant forms a monomer that is catalytically active, but with reduced catalytic efficiency, displaying 8% of the specific activity of the wild-type enzyme. The Michaelis constants for the substrates pyruvate and for (S)-aspartate semialdehyde increase by an order of magnitude. L197D/Y107W is expressed as a folded monomer
L51K
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site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
L51T
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme and is sill sensitive to L-lysine
Q196D
removal of hydrogen bonds and charge-charge repulsion, shortened side chain places charged carboxyl groups proximal at interface
Q234D
removal of hydrogen bond and charge-charge repulsion with negatively charged E175. Quaternary structure appears closest to that of the wild-type enzyme
R138A
activity is approximately 0.1% of wild-type activity, Km-value for L-aspartate 4-semialdehyde is significantly higher than the wild-type value, shows the same IC50 values as the wild-type enzyme, but different partial inhibition patterns
R138H
activity is approximately 0.1% of wild-type activity, Km-value for L-aspartate 4-semialdehyde is significantly higher than the wild-type value, shows the same IC50 values as the wild-type enzyme, but different partial inhibition patterns
T44S
the active site is intact, returns much but not all activity likely due to the flexibility of Ser44. Increased flexibility in the active site, which appears to facilitate the binding/reaction of substrate analogues
T44V
site-directed mutagenesis, reduced activity, structure is similar to the wild-type enzyme
Y107F
Y133F
site-directed mutagenesis, reduced activity, structure is similar to the wild-type enzyme
H118Y
Escherichia coli LATR11
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mutant enzyme H56K is more conducive to L-lysine production than mutant H118Y
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H56K
Escherichia coli LATR11
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mutant enzyme H56K is more conducive to L-lysine production than mutant H118Y
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A49P
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site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme and is still sensitive to L-lysine
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E84T
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site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme and is insensitive to L-lysine
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H56K
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site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme and is insensitive to L-lysine
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L51T
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme and is sill sensitive to L-lysine
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A204R
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site-directed mutagenesis, disruption of the native tetramer formation by targeting the dimer-dimer interface. The mutant enzyme is a dimeric protein with an identical fold and active-site structure to the tetrameric wild-type enzyme
additional information
Q81WN7
dimeric mutant of the enzyme, retains only 1.8% of the total catalytic activity of the wild-type tetrameric enzyme
L170E/G191E
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dimeric mutant of the enzyme, retains only 1.8% of the total catalytic activity of the wild-type tetrameric enzyme
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site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme and is insensitive to L-lysine
H56K
mutant enzyme H56K is more conducive to L-lysine production than mutant H118Y
catalytically active, significant decrease in activity. Is not inactivated when incubated with pyruvate and the reducing agent sodium borohydride. Negligible heat production associated with pyruvate binding to the mutant enzyme, consistent with the lack of Schiff base formation
K161A
substantially diminished binding affinity of pyruvate, the surrounding active site scaffold is unable to compensate the entropic penalty associated with ligand localisation in the absence of Schiff-base formation
site-directed mutagenesis, reduced activity, structure is similar to the wild-type enzyme
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mutagenesis of the lysine binding sites of the Corynebacterium glutamicum enzyme according to the residues in the Escherichia coli enzyme does not conver the expected feedback inhibition but an activation of the nezyme by L-lysine
additional information
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mutagenesis of the lysine binding sites of the Corynebacterium glutamicum enzyme according to the residues in the Escherichia coli enzyme does not conver the expected feedback inhibition but an activation of the nezyme by L-lysine
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additional information
detailed structural properties of the mutant enzymes based on the crystal structure models
additional information
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detailed structural properties of the mutant enzymes based on the crystal structure models
additional information
C-terminal truncated DHDPS (H225*), exhibits a dramatic reduction in both solubility and stability. Equilibrating mixture of quaternary states. The substrate, pyruvate, and the feedback inhibitor, (S)-lysine, both have a positive effect on thermostability of C-terminal truncated DHDPS (H225*)
additional information
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C-terminal truncated DHDPS (H225*), exhibits a dramatic reduction in both solubility and stability. Equilibrating mixture of quaternary states. The substrate, pyruvate, and the feedback inhibitor, (S)-lysine, both have a positive effect on thermostability of C-terminal truncated DHDPS (H225*)
additional information
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disruption of quaternary structure of DHDPS generates a functional monomer that is no longer inhibited by lysine, overview
additional information
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feedback inhibition of the Escherichia coli enzyme by lysine is successfully alleviated after substitution of the residues around the inhibitor's binding sites with those of the Corynabacterium glutamicum enzyme
additional information
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feedback inhibition of the Escherichia coli enzyme by lysine is successfully alleviated after substitution of the residues around the inhibitor's binding sites with those of the Corynabacterium glutamicum enzyme
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additional information
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expression of dapA gene of E coli, insensitive to feedback-inhibition by L-lysine
additional information
mutant construction by gene replacement of gene dapA (PA1010) via the sacB-based strategy
additional information
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mutant construction by gene replacement of gene dapA (PA1010) via the sacB-based strategy
additional information
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construction of mutants Tm-DHDPS-DELTAAsp168, DELTAAsp171, or DELTAArg237 by mutating charged residues, reduction of the number of salt bridges at one of the two tetramerization interface of the enzyme and its interactions results in variants with altered quaternary structure, e.g. monomeric, as shown by analytical ultracentrifugation, gel filtration liquid chromatography, and small angle X-ray scattering, and X-ray crystallographic studies, overview