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Information on EC 4.3.3.7 - 4-hydroxy-tetrahydrodipicolinate synthase
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4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthaseIUBMB Comments
The reaction can be divided into three consecutive steps: Schiff base formation with pyruvate, the addition of L-aspartate-semialdehyde, and finally transimination leading to cyclization with simultaneous dissociation of the product. The product of the enzyme was initially thought to be (S)-2,3-dihydrodipicolinate [1,2], and the enzyme was classified accordingly as EC 4.2.1.52, dihydrodipicolinate synthase. Later studies of the enzyme from the bacterium Escherichia coli have suggested that the actual product of the enzyme is (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate , and thus the enzyme has been reclassified as 4-hydroxy-tetrahydrodipicolinate synthase. However, the identity of the product is still controversial, as more recently it has been suggested that it may be (S)-2,3-dihydrodipicolinate after all .
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Word Map
- 4.3.3.7
- diaminopimelate
-
4.2.1.52
-
s-lysine
- drug development
- homoserine
- meso-diaminopimelate
- aspartokinase
- l-threonine
-
s-aspartate
- s-2-aminoethyl-l-cysteine
-
feedback-insensitive
-
lysine-insensitive
- beta-semialdehyde
- pharmacology
-
l-aspartate-beta-semialdehyde
-
2.7.2.4
-
aspartate-derived
- medicine
- synthesis
- agriculture
- biotechnology
- industry
- food industry
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
dhdps, dihydrodipicolinate synthase, dhdps2, pa1010, dihydrodipicolinic acid synthase, cjdhdps, cdhdps, 4-hydroxy-tetrahydrodipicolinate synthase, mrsa-dhdps, dhdpa synthase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DapA
DHDPS
dihydrodipicolinate synthase
dihydrodipicolinic acid synthase
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dihydropicolinate synthetase
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HTPA synthase
MosA
MosA protein
MRSA-DHDPS
pyruvate-aspartic semialdehyde condensing enzyme
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Rv2753c
synthase, dihydrodipicolinate
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VEG81
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Vegetative protein 81
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additional information
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the enzyme belongs to the TIM-barrel family of enzymes
DHDPS
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DHDPS
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DHDPS
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DHDPS
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dihydrodipicolinate synthase
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dihydrodipicolinate synthase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
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pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
pyruvate binds to the enzyme first by forming a Schiff base with the epsilon-amino group of Lys161. After release of the first water molecule L-aspartate-4-semialdehyde binds to the active site and the condensation reaction to form 2,3-dihydrodipicolinate takes place
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pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the reaction is initiated by an nucleophilic attack of the epsilon-amino group of active site lysine to the C2 atom of pyruvate with subsequent imine formation. Tautomerization of the imine to the enamine creates the nucleophile necessary for the attack of the aldehyde group of L-aspartate semialdehyde. Cyclization of the substrate coupled with transamination leads to stepwise detachment from the active site
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pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
ping-pong mechanism, pyruvate binds as a Schiff base to Lys161. After aldol reaction with L-aspartate-4-semialdehyde and transamination the product is released
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pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
ping-pong kinetic and catalytic mechanism involves a catalytic triad which consists of Tyr133, Thr44, and Tyr107, overview
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
reaction mechanism including Schiff base formation, tautomerization, and cyclization, overview
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pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
ping-pong kinetic reaction mechanism
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pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
ping-pong mechanism, in which pyruvate binds as a Schiff base to an active-site lysine residue (Lys162 in Agrobacterium tumefaciens)
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
reaction steps, overview
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site lysine residue (Lys161 in Escherichia coli DHDPS) forming a Schiff base, ping-pong kinetic reaction mechanism via enamine intermediate, overview
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the reaction proceeds via a ping-pong kinetic mechanism in which pyruvate binds and forms a Schiff base to an active-site lysine residue (Lys184 in Vitis vinifera enzyme). L-aspartate-4-semialdehyde then reacts with the resultant enamine and following cyclization forms the product (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
ping-pong mechanism, in which pyruvate binds as a Schiff base to an active-site lysine residue (Lys162 in Agrobacterium tumefaciens)
Agrobacterium tumefaciens C58 / ATCC 33970
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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SYSTEMATIC NAME
IUBMB Comments
L-aspartate-4-semialdehyde hydro-lyase [adding pyruvate and cyclizing; (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate-forming]
The reaction can be divided into three consecutive steps: Schiff base formation with pyruvate, the addition of L-aspartate-semialdehyde, and finally transimination leading to cyclization with simultaneous dissociation of the product. The product of the enzyme was initially thought to be (S)-2,3-dihydrodipicolinate [1,2], and the enzyme was classified accordingly as EC 4.2.1.52, dihydrodipicolinate synthase. Later studies of the enzyme from the bacterium Escherichia coli have suggested that the actual product of the enzyme is (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate [3], and thus the enzyme has been reclassified as 4-hydroxy-tetrahydrodipicolinate synthase. However, the identity of the product is still controversial, as more recently it has been suggested that it may be (S)-2,3-dihydrodipicolinate after all [5].
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CAS REGISTRY NUMBER
COMMENTARY
9055-59-8
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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
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
pyruvate + (R,S)-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
pyruvate + DL-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
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-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
characterization of thermostable enzyme features, substrate specificity tested, activity measurements at elevated temperature of 60°C
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-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
branch point reaction in the biosynthesis of lysine
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
first step in the biosynthesis of lysine, overview
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
biosynthesis of (S)-lysine and meso-diaminopimelate
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-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
diketopimelic acid derivatives designed as mimics of the acyclic enzyme-bound condensation product of (S)-aspartate 4-semialdehyde and pyruvate, inhibition analysis
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-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
reaction mechanism and active site analyzed, inhibition by the substrate analog beta-hydroxypyruvate
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-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
role of Tyr107 residue, located at the tight-dimer interface between two monomers, participates in a catalytic triad of residues during catalysis
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-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
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-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
first step in the biosynthesis of lysine, overview
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
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-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
biosynthesis of (S)-lysine and meso-diaminopimelate, compounds of bacterial cell walls
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?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
mechanistic insight into catalysis, structural features, evolution of quaternary structure
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-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
biosynthesis of (S)-lysine and meso-diaminopimelate, compounds of bacterial cell walls
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-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
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-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
mechanistic insight into catalysis, structural features, evolution of quaternary structure
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
catalyses the branch point in lysine biosynthesis
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-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
bi-bi ping-pong substrate model
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-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
Agrobacterium tumefaciens C58 / ATCC 33970
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
Agrobacterium tumefaciens C58 / ATCC 33970
bi-bi ping-pong substrate model
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
Agrobacterium tumefaciens C58 / ATCC 33970
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-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
(S)-aspartate-4-semialdehyde binds cooperatively in the presence of (S)-lysine with an average cooperativity coefficient n = 1.3, and the cooperativity of binding increases at near-KM concentrations of pyruvate with an average cooperativity coefficient n = 1.0
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?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site Lys161 forming a Schiff base. Subsequent tautomerization to the enamine and aldol-type reaction with (S)-aspartate-4-semialdehyde then generates an acyclic enzyme-bound intermediate. Transimination of the acyclic intermediate yields the cyclic alcohol (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, with simultaneous release of the active site lysine residue
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?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
Q81WN7
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
Q81WN7
active sites are similiar to Escherichia coli DHDPS
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
Q81WN7
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
-
active sites are similiar to Bacillus anthracis DHDPS
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
condensation reaction between both substrates via the formation of a Schiff base intermediate between pyruvate and the absolutely conserved active-site lysine. Although lysine 161 is important in the wild-type DHDPS-catalysed reaction, it is not absolutely essential for catalysis
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
pyruvate is a weak binder (0.023 mM) and L-aspartate 4-semialdehyde does not interact with the enzyme in the absence of a Schiff-base with pyruvate. Lys161 plays a crucial role in providing the thermodynamic force for the association of pyruvate with the DHDPS active site
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
slightly higher affinity for L-aspartate 4-semialdehyde and somewhat lower affinity for pyruvate than the Escherichia coli enzyme, whereby the catalytic activity is similar
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + 2 H2O
slightly higher affinity for L-aspartate 4-semialdehyde and somewhat lower affinity for pyruvate than the Escherichia coli enzyme, whereby the catalytic activity is similar
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
lysine insensitivity of dihydrodipicolinate synthase analyzed, catalytic lysine residue forms a Schiff base adduct with pyruvate, active site lysine residues (K176a, K176b)
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
branch poit of (S)-lysine biosynthesis
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
substrate protection and inhibition experiments
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
isothermal titration calorimetry (ITC) to study Schiff base formation between an enzyme and its substrate, pyruvate condenses with an active site lysine residue (Lys161 in MosA)
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
isothermal titration calorimetry (ITC) to study Schiff base formation between an enzyme and its substrate, pyruvate condenses with an active site lysine residue (Lys161 in MosA)
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
?
-
synthesis of the precursor of dipicolinic acid which plays a key role in bacterial sporulation process
-
-
?
L-aspartate-4-semialdehyde + pyruvate
?
-
first enzyme in the meso-diaminopimelate and L-lysine branch of the aspartate pathway
-
-
?
L-aspartate-4-semialdehyde + pyruvate
?
-
biosynthesis of lysine via the diaminopimelate pathway
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
(4S)-4-hydroxy-2,3,4,5-terahydro-(2S)-dipicolinic acid is the initial but instable product
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
D-isomer inactive
-
?
pyruvate + (R,S)-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
-
?
pyruvate + (R,S)-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes a step of the diaminopimelate biosynthetic pathway of lysine
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes a step of the diaminopimelate biosynthetic pathway of lysine
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the first committed step in the lysine biosynthesis pathway of plants
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the first committed step in the diaminopimelate pathway
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the first committed step in the diaminopimelate pathway
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
2,3-dihydrodipicolinate + ?
-
2,3-dihydrodipicolinate is the product of the synthase reaction. One or more of the NMR peaks previously assigned to the product of the dihydrodipicolinate synthase reaction, presumed to be (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate, actually arises from a non-enzymatic reaction
-
-
?
pyruvate + L-aspartate-4-semialdehyde
2,3-dihydrodipicolinate + ?
-
2,3-dihydrodipicolinate is the product of the synthase reaction. One or more of the NMR peaks previously assigned to the product of the dihydrodipicolinate synthase reaction, presumed to be (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate, actually arises from a non-enzymatic reaction
-
-
?
additional information
?
-
-
no reaction with oxaloacetic acid, phosphoenolpyruvate, glutamic semialdehyde, N-acetylaspartic semialdehyde, succinic semialdehyde
-
-
?
additional information
?
-
-
no activity with (R)-aspartate 4-semialdehyde
-
?
additional information
?
-
-
the quaternary structure plays a significant role in substrate specificity, overview
-
-
?
additional information
?
-
-
coupled assay with dihydrodipicolinate reductase
-
-
?
additional information
?
-
-
coupled assay with dihydrodipicolinate reductase
-
-
?
additional information
?
-
-
no activity with (R)-aspartate 4-semialdehyde
-
?
additional information
?
-
-
isozyme MtDHDPS1, followed by isozyme MtDHDPS4, exhibits the highest activity, while activity of isozyme MtDHDPS2 and especially of isozyme MtDHDPS3 is low
-
-
?
additional information
?
-
-
isozyme MtDHDPS1, followed by isozyme MtDHDPS4, exhibits the highest activity, while activity of isozyme MtDHDPS2 and especially of isozyme MtDHDPS3 is low
-
-
?
additional information
?
-
the active site is formed by residues Thr44, Tyr107 and Tyr133, stereochemically suitable for catalytic function
-
-
?
additional information
?
-
-
the active site is formed by residues Thr44, Tyr107 and Tyr133, stereochemically suitable for catalytic function
-
-
?
additional information
?
-
-
the active site of the monomer is well conserved, with most active-site residues in the same conformation
-
-
?
additional information
?
-
coupled assay with dihydrodipicolinate reductase
-
-
?
additional information
?
-
-
coupled assay with dihydrodipicolinate reductase
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
branch point reaction in the biosynthesis of lysine
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
first step in the biosynthesis of lysine, overview
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
first step in the biosynthesis of lysine, overview
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
(S)-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
catalyses the branch point in lysine biosynthesis
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
Agrobacterium tumefaciens C58 / ATCC 33970
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
Agrobacterium tumefaciens C58 / ATCC 33970
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site Lys161 forming a Schiff base. Subsequent tautomerization to the enamine and aldol-type reaction with (S)-aspartate-4-semialdehyde then generates an acyclic enzyme-bound intermediate. Transimination of the acyclic intermediate yields the cyclic alcohol (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, with simultaneous release of the active site lysine residue
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
(S)-aspartate-4-semialdehyde + pyruvate
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate 4-semialdehyde + pyruvate
dihydrodipicolinate + H2O
-
-
-
?
L-aspartate-4-semialdehyde + pyruvate
?
-
synthesis of the precursor of dipicolinic acid which plays a key role in bacterial sporulation process
-
-
?
L-aspartate-4-semialdehyde + pyruvate
?
-
first enzyme in the meso-diaminopimelate and L-lysine branch of the aspartate pathway
-
-
?
L-aspartate-4-semialdehyde + pyruvate
?
-
biosynthesis of lysine via the diaminopimelate pathway
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes a step of the diaminopimelate biosynthetic pathway of lysine
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes a step of the diaminopimelate biosynthetic pathway of lysine
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the first committed step in the lysine biosynthesis pathway of plants
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the first committed step in the diaminopimelate pathway
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
the enzyme catalyzes the first committed step in the diaminopimelate pathway
-
-
?
pyruvate + L-aspartate-4-semialdehyde
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
-
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
neither NAD+ nor NADP+ are involved in the production of dipicolinic acid
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1SR,3R,5S)-1-hydroxy-3,5-bis(methoxycarbonyl)thiomorpholin-1-ium
-
30 mM, 18% inhibition
(1SS,3R,5S)-1-hydroxy-3,5-bis(methoxycarbonyl)thiomorpholin-1-ium
-
9 mM, 48% inhibition
(3R,5R)-thiomorpholine-3,5-dicarboxylic acid 1,1-dioxide
-
50 mM, 11% inhibition
(3R,5S)-thiomorpholine-3,5-dicarboxylic acid 1,1-dioxide
-
50 mM, 14% inhibition
(S)-aspartate-4-semialdehyde
substrate inhibition
(S)-Lys
partial mixed inhibition with respect to pyruvate and partial non-competitive inhibition with resoect to L-aspartate 4-semialdehyde
2-(4-carbamoylphenyl)-2-oxoacetic acid
maximal inhibition of 15% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
2-hydroxyheptanediamide
maximal inhibition of 21% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
2-hydroxyheptanedioic acid
maximal inhibition of 74% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
2-oxohexanedioic acid
maximal inhibition of 40% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
2-oxopentanedioic acid
maximal inhibition of 15% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
2-oxopimelate
maximal inhibition of 88% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase. This assay is able to measure DapA enzyme kinetics if the dihydrodipicolinate reductase DapB is present in excess, because under these conditions DapA becomes rate limiting
2-phenoxyacetic acid
maximal inhibition of 4% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
3-Fluoropyruvate
-
competitive inhibitor of DHDPS, and a competitive substrates
3-hydroxy-2-oxopropanoate
time-dependent inhibition, qualitatively followed by mass spectrometry, initial noncovalent adduct formation, followed by the slow formation of the covalent adduct
3-hydroxypyruvate
-
competitive inhibitor of DHDPS and a competitive substrate
4-((2-amino-2-oxoethyl)sulfonyl) butanoic acid
maximal inhibition of 29% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
4-((2-amino-2-oxoethyl)thio)butanoic acid
maximal inhibition of 15% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
4-(2,4,5-trioxoimidazolidin-1-yl)butanoic acid
maximal inhibition of 21% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
4-amino benzoic acid
maximal inhibition of 8% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
4-amino-2-hydroxybenzoic acid
maximal inhibition of 4% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
4-[amino(oxo)acetyl]benzoic acid
maximal inhibition of 34% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
4-[carboxy(hydroxy)methyl]benzoic acid
maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
4-[methyl(oxalo)amino]butanoic acid
maximal inhibition of 39% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
5-(carbamoylamino)-5-oxopentanoic acid
maximal inhibition of 40% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
5-(carbamoylthio)pentanoic acid
maximal inhibition of 65% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
5-butylpyridine-2-carboxylic acid
maximal inhibition of 5% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
7-ethoxy-6,7-dioxoheptanoic acid
maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
benzoic acid
maximal inhibition of 2% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
bislysine
-
bislysine is a mixed partial inhibitor with respect to the first substrate, pyruvate, and a noncompetitive partial inhibitor with respect to L-aspartate-4-semialdehyde
carboxycarbonyl-benzoic acid
maximal inhibition of 22% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
dimethyl (3R,5S)-thiomorpholine-3,5-dicarboxylate 1,1-dioxide
-
20 mM, 19% inhibition; 20 mM, 6% inhibition
dimethyl chelidamate
-
IC50: 14 mM. 99% inhibition at 50 mM, noncompetitive with respect to both substrates
dimethyl-(2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
-
slow inhibition
dimethyl-2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetate)
-
slow-tight inhibition
ethyl 4-((2-amino-2-oxoethyl)sulfinyl)butanoate
maximal inhibition of 31% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
ethyl 4-((2-amino-2-oxoethyl)sulfonyl)butanoate
maximal inhibition of 12% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
ethyl 4-((2-amino-2-oxoethyl)thio)butanoate
maximal inhibition of 21% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
ethyl 5-(carbamoylsulfanyl)pentanoate
maximal inhibition of 34% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
ethyl [(4-amino-4-oxobutyl)(methyl)amino](oxo)acetate
maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
heptanedioic acid
maximal inhibition of 10% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
hydroxy[4-(methoxycarbonyl)phenyl]acetic acid
maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
L-aspartate
competitive inhibition, L-aspartate 4-semialdehyde as varied substrate
lysine
inhibition of wild-type DHDPS by lysine with respect to pyruvate is partial and uncompetitive, and partial non-competitive with respect to L-aspartate 4-semialdehyde. Ethanolamine, n-butylamine, 1-amino-2-propanol, 3-amino-1-propanol, iso-butylamine and Tris-HCl cannot rescue activity
methoxycarbonyl-phenyloxoacetic acid
maximal inhibition of 29% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
methyl 3-oxohexanoate
maximal inhibition of 5% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
methyl 4-(2,4,5-trioxoimidazolidin-1-yl)butanoate
maximal inhibition of 38% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
methyl 4-[(2-ethoxy-2-oxoethyl)(methyl)amino]butanoate
maximal inhibition of 42% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
-
methyl 4-[amino(oxo)acetyl]benzoate
maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
methyl 5-(carbamoylamino)-5-oxopentanoate
maximal inhibition of 65% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
methyl 6-oxo-6-(2H-tetrazol-5-yl)hexanoate
maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
methyl 7-amino-6,7-dioxoheptanoate
maximal inhibition of 24% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
methyl 7-amino-6-hydroxy-7-oxoheptanoate
maximal inhibition of 28% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
N1-(4-amino-4-oxobutyl)-N1-methylethanediamide
maximal inhibition of 40% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
NaBH4
NaBH4 reduction of the pyruvyl-Schiff-base intermediate results in enzyme inactivation
oxaloacetate
non-competitive inhibition, pyruvate as varied substrate
pyruvate
substrate inhibition
Sodium borohydride
wild-type DHDPS is inactivated when incubated with pyruvate, whereas incubation with L-aspartate 4-semialdehyde has no effect
Succinate-semialdehyde
reversible inhibitor which is competitive with respect to L-aspartate-4-semialdehyde and uncompetitive with respect to pyruvate
[(4-amino-4-oxobutyl)(methyl)amino](oxo)acetic acid
maximal inhibition of 44% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase
(2R,6S)-piperidine-2,6-dicarboxylic acid
-
IC50: 20 mM, 83% inhibition at 50 mM
(2R,6S)-piperidine-2,6-dicarboxylic acid
-
20 mM, 43% inhibition; 20 mM, 77% inhibition
(S)-lysine
allosteric feedback inhibition; allosteric feedback inhibition; allosteric feedback inhibition; allosteric feedback inhibition; allosteric feedback inhibition; allosteric feedback inhibition; allosteric feedback inhibition, allosteric site modeling; allosteric feedback inhibition, allosteric site modeling; allosteric feedback inhibition, allosteric site modeling; allosteric feedback inhibition, allosteric site modeling
(S)-lysine
increasing amounts of (S)-lysine (0-200 mM) added, not inhibited under physiological conditions, binding site of the allosteric inhibitor lysine appears not to be conserved
(S)-lysine
-
feedback inhibition, the tetrameric enzyme has two allosteric sites, each of which binds two molecules of lysine. Lysine binds highly cooperatively, and primarily to the F form of the enzyme during the ping-pong mechanism. (S)-Lysine is an uncompetitive partial inhibitor with respect to its first substrate, pyruvate, and a mixed partial inhibitor with respect to its second substrate, (S)-aspartate-4-semialdehyde
(S)-lysine
mutant enzymes R138H and R138A show the same IC50 values as the wild-type enzyme, but different partial inhibition patterns
(S)-lysine
-
partial mixed inhibition with respect to its first substrate, pyruvate
(S)-lysine
partial mixed inhibition with respect to (S)-aspartate 4-semialdehyde, partial non-ncompetitive inhibition with respect to pyruvate in wild-type and in Y107W mutant, Y107W mutant still retains over 25% of uninhibited activity, even at high inhibitor concentrations compared to the wild-type enzyme retaining less than 10% of normal activity
(S)-lysine
-
feedback inhibition, 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
(S)-lysine
no significant conformational change between the pyruvate-bound and (S)-lysine-bound enzyme, presence of substrate has substantial effect on the nature of enzyme-inhibitor association, solvent plays a key role in binding of inhibitor
2-oxobutyrate
forms a Schiff base with MosA protein, competitive inhibition
3-Bromopyruvate
competitive inhibition, pyruvate as varied substrate
4-oxo-1,4-dihydropyridine-2,6-dicarboxylic acid
-
i.e. chelidamic acid, IC50: 22 mM, 99% inhibition at 50 mM, uncompetitive inhibitor with respect to both substrates
4-oxo-1,4-dihydropyridine-2,6-dicarboxylic acid
-
20 mM, 73% inhibition
4-oxo-1,4-dihydropyridine-2,6-dicarboxylic acid
-
20 mM, 83% inhibition
cis-(1SS,3R5S)-3,5-thiomorpholinedicarboxylic acid, dimethyl ester, 1-oxide
-
20 mM, 8% inhibition
cis-(1SS,3R5S)-3,5-thiomorpholinedicarboxylic acid, dimethyl ester, 1-oxide
-
20 mM, 8% inhibition
cis-(1SS,3R5S)-3,5-thiomorpholinedicarboxylic acid, dimethyl ester, 1-oxide
-
20 mM, 10% inhibition
dimethyl (2R,6S)-piperidine-2,6-dicarboxylate
-
20 mM, 24% inhibition; 20 mM, 99% inhibitione
dimethyl (3R,5R)-thiomorpholine-3,5-dicarboxylate
-
20 mM, 19% inhibition
dimethyl (3R,5R)-thiomorpholine-3,5-dicarboxylate 1,1-dioxide
-
50 mM, 12% inhibition
dimethyl (3R,5R)-thiomorpholine-3,5-dicarboxylate 1,1-dioxide
-
20 mM, 14% inhibition
dimethyl (3R,5R)-thiomorpholine-3,5-dicarboxylate 1,1-dioxide
-
20 mM, 6% inhibition; 20 mM, 7% inhibition
dimethyl (3R,5R)-thiomorpholine-3,5-dicarboxylate 1-oxide
-
20 mM, 7% inhibition
dimethyl (3R,5R)-thiomorpholine-3,5-dicarboxylate 1-oxide
-
20 mM, 7% inhibition
dimethyl (3R,5S)-thiomorpholine-3,5-dicarboxylate
-
20 mM, 23% inhibition
dimethyl 4-oxo-1,4-dihydropyridine-2,6-dicarboxylate
-
20 mM, 84% inhibition
dimethyl 4-oxo-1,4-dihydropyridine-2,6-dicarboxylate
-
20 mM, 88% inhibition
L-aspartate 4-semialdehyde
Q81WN7
DHDPS is subject to substrate inhibition by L-aspartate 4-semialdehyde
L-aspartate 4-semialdehyde
uncompetitive inhibition by high concentrations of, no overcome by increasing pyruvate concentrations from 5 to 15 mM
L-aspartate 4-semialdehyde
competitive inhibition at high substrate concentrations
L-aspartate 4-semialdehyde
is subject to substrate inhibition by high concentrations
L-lysine
-
allosteric inhihitor. Allostery is mediated by changes in the extent of thermally activated conformational fluctuations
L-lysine
lack of feedback inhibition, not regulated under normal physiological conditions
L-lysine
no difference in its sensitivity or behaviour with respect to L-lysine when compared to the wild-type
L-lysine
binding interaction of L-lysine is characterised as a cooperative event in which an entropic pre-organisation step precedes a secondary enthalpic association. This allosteric association is of a mixed competitive nature in which heterotropic ligand cooperativity is observed to subtly influence the binding events
L-lysine
-
inhibition of the tetrameric wild-type enzyme, but not of the disrupted minimeric mutant enzyme. Allosteric binding by two molecules of (S)-lysine at the DHDPS tight-dimer interface cleft has been observed to operate via a cooperative mechanism and to result in incomplete partial mixed inhibition, inhibition kinetics, overview
L-lysine
is significantly more sensitive to feedback inhibition than Escherichia coli DHDPS
L-lysine
binds at three sites to the enzyme, binding structure, overview
L-lysine
feedback inhibition, binding of lysine to the allosteric cleft of the enzyme, cooperative binding, structural mechanism for allosteric inhibition, overview. With respect to L-aspartate-4-semialdehyde, lysine is a noncompetitive inhibitor
L-threonine
-
at 100 mM 23% residual activity, at 100 mM 33% residual activity
pyridine-2,6-dicarboxylic acid
-
20 mM, 75% inhibition; 20 mM, 80% inhibition
Succinic semialdehyde
uncompetitive inhibition, L-aspartate 4-semialdehyde as varied substrate
trans-(1SS,3R5S)-3,5-thiomorpholinedicarboxylic acid, dimethyl ester, 1-oxide
-
20 mM, 20% inhibition
trans-(1SS,3R5S)-3,5-thiomorpholinedicarboxylic acid, dimethyl ester, 1-oxide
-
20 mM, 14% inhibition; 20 mM, 22% inhibition
trans-(1SS,3R5S)-3,5-thiomorpholinedicarboxylic acid, dimethyl ester, 1-oxide
-
20 mM, 12% inhibition
additional information
Q81WN7
is not inhibited by 1-100 mM L-lysine or L-isoleucine
-
additional information
-
is not inhibited by 1-100 mM L-lysine or L-isoleucine
-
additional information
-
not inhibitory: ATP, ADP, AMP, citric acid, L-malic acid, 2-oxoglutaric acid, fumaric acid, succinic acid, L-glutamic acid, L-threonine
-
additional information
-
no inhibition by (S)-aspartate 4-semialdehyde, but inhibition occurs by a derivative that is built of the compounbd in the enzyme preparation by ozonolysis
-
additional information
-
no inhibition by dipicolinic acid methyl ester, (3R,5S)-thiomorpholine-3,5-dicarboxylic acid compound 20b, (3R,5R)-thiomorpholine-3,5-dicarboxylic acid, compound 23, compound 24b, dimethyl (3R,5S)thiomorpholine-3,5-dicarboxylate 1,1-dioxide
-
additional information
inhibition studies by using 4-oxo-heptenedioic acid analogues, determination of second-order rate constants of inactivation, substrate co-incubation studies show that the inhibitors act at the active-site, interaction analyzed by mass spectrometry, sites of enzyme alkylation determined
-
additional information
new constrained inhibitors of DHDPS identified and tested, time-dependent inhibition and substrate protection, dimethyl 2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate] discovered as a relatively potent inhibitor of DHDPS enzyme, validates constrained acyclic-intermediate model as a potential inhibitor lead, modifications of the aromatic ring are possible and may result in improvements in activity
-
additional information
-
no substrate inhibition by (S)-aspartate 4-semialdehyde
-
additional information
-
the substrate specificity of the enzyme, two pyruvate analogues, previously classified as weak competitive inhibitors, are turned over productively by DHDPS, NMR spectroscopy, overview
-
additional information
-
1,3-phenylene bis(ketoacid) derivatives as enzyme inhibitors, overview. Ketoacid derivatives act as slow and slow-tight binding inhibitors with either an encounter complex or a condensation product for the slow and slow-tight binding inhibitors, respectively, modeling, overview. No or poor inhibition by dimethyl 2,2'-benzene-1,3-diylbis(oxoacetate), (2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoic acid], and dimethyl-2,2'-(2-methoxy-1,3-phenylene)bis(2-oxoacetate)
-
additional information
molecular descriptors analysis shows that ligands with polar surface area of 91.7 A are likely inhibitors
-
additional information
-
molecular descriptors analysis shows that ligands with polar surface area of 91.7 A are likely inhibitors
-
additional information
-
not inhibitory: iodoacetate, iodoacetamide, p-chloromercuribenzoate
-
additional information
not inhibited by (S)-lysine, suggesting that feedback control of the lysine biosynthetic pathway evolves later in the bacterial lineage
-
additional information
-
not inhibited by (S)-lysine, suggesting that feedback control of the lysine biosynthetic pathway evolves later in the bacterial lineage
-
additional information
-
is insensitive to L-lysine inhibition, produces no binding isotherm upon L-lysine addition in either the absence or presence of pyruvate
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R,3S,6S)-2,6-diamino-3-hydroxyheptanedioic acid
-
134% of the activity without
L-lysine
-
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 enzyme by L-lysine
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Bacterial Infections
Mis-annotations of a promising antibiotic target in high-priority gram-negative pathogens.
Cat-Scratch Disease
Cloning, expression, purification, crystallization and X-ray diffraction analysis of dihydrodipicolinate synthase from the human pathogenic bacterium Bartonella henselae strain Houston-1 at 2.1?Å resolution.
Dehydration
Evolution of enzymatic activities in the enolase superfamily: galactarate dehydratase III from Agrobacterium tumefaciens C58.
Hyperoxaluria, Primary
Dihydrodipicolinate Synthase: Structure, Dynamics, Function, and Evolution.
Starvation
Regulation of dihydrodipicolinate synthase and aspartate kinase in Bacillus subtilis.
Tuberculosis
A tetrameric structure is not essential for activity in dihydrodipicolinate synthase (DHDPS) from Mycobacterium tuberculosis.
Tuberculosis
Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DapA (Rv2753c) from Mycobacterium tuberculosis.
Tuberculosis
Crystal structure and kinetic study of dihydrodipicolinate synthase from Mycobacterium tuberculosis.
Tuberculosis
Identification of potential leads against 4-hydroxytetrahydrodipicolinate synthase from Mycobacterium tuberculosis.
Tuberculosis
Inhibiting dihydrodipicolinate synthase across species: towards specificity for pathogens?
Tuberculosis
Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues.
Tuberculosis
Molecular Interaction of Novel Compound 2-Methylheptyl Isonicotinate Produced by Streptomyces sp. 201 with Dihydrodipicolinate Synthase (DHDPS) Enzyme of Mycobacterium tuberculosis for its Antibacterial Activity.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.22
(S)-aspartate 4-semialdehyde
similar to those of DHDPS enzyme of Escherichia coli
0.38
(S)-aspartate 4-semialdehyde
by adding 20 mM pyruvate, at 60°C
0.92
(S)-aspartate 4-semialdehyde
modeled with substrate inhibition, at 60°C
0.137
(S)-aspartate-4-semialdehyde
-
recombinant mutant H56K, pH 8.0, temperature not specified in the publication
0.16 - 0.32
(S)-aspartate-4-semialdehyde
pH and temperature not specified in the publication
0.248
(S)-aspartate-4-semialdehyde
-
recombinant mutant E84T, pH 8.0, temperature not specified in the publication
0.3
(S)-aspartate-4-semialdehyde
-
recombinant wild-type enzyme, pH 8.0, temperature not specified in the publication
0.052
L-aspartate 4-semialdehyde
at 30°C, in 100 mM HEPES buffer, pH 8.0
0.12
L-aspartate 4-semialdehyde
mutant K161R, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
0.12
L-aspartate 4-semialdehyde
wild-type, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
0.15
L-aspartate 4-semialdehyde
mutants Q196D, D193A and D193Y, at 30°C
0.15
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp237
0.17
L-aspartate 4-semialdehyde
pH 8.0, 37°C, recombinant His-tagged enzyme
0.18
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp237
0.23
L-aspartate 4-semialdehyde
C-terminal truncated DHDPS (H225*), at 30°C, in 150 mM HEPES, pH 8.0, 0.16 mM NADPH, 50 microg/ml DHDPR
0.23
L-aspartate 4-semialdehyde
mutant K161A, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
0.23
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp171/Arg237
0.23
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant wild-type enzyme
0.29
L-aspartate 4-semialdehyde
polyhistidine-tagged wild-type DHDPSR
0.32
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp171/Arg237
0.36
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant wild-type enzyme
0.42
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp171
0.43
L-aspartate 4-semialdehyde
-
pH 8.0, 30°C, recombinant wild-type enzyme
0.46
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp171
0.63
L-aspartate 4-semialdehyde
reaction mixture includes 100 mM Tris-HCl, 2.5 mM pyruvate, 0.05-0.1 microg dihydrodipicolinate synthase and 0.2 mM NADPH, from 5.6 to 22.4 mM plots deviate from typical Michaelis-Menten kinetics, increased concentration fits an uncompetitive substrate inhibition model
1.1
L-aspartate 4-semialdehyde
-
pH 8.0, 30°C, recombinant mutant A204R
1.1
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168/Asp171
1.2
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168/Asp237
1.3
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168/Asp171
1.5
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168
1.7
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168/Asp237
2.2
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168
0.14
L-aspartate-4-semialdehyde
30°C, pH not specified in the publication
0.05
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp237
0.07
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp171
0.08
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp171/Arg237
0.08
pyruvate
-
pH not specified in the publication, 30°C, recombinant wild-type enzyme
0.1
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp237
0.11
pyruvate
similar to those of DHDPS enzyme of Escherichia coli
0.15
pyruvate
wild-type, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
0.15
pyruvate
-
pH not specified in the publication, 45°C, recombinant wild-type enzyme
0.16
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp171
0.18
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp171/Arg237
0.31 - 0.44
pyruvate
pH and temperature not specified in the publication
0.32
pyruvate
2.5 mM pyruvate replaced by 0.1-2 mM, no substrate inhibition observed at high concentrations of pyruvate
0.37
pyruvate
C-terminal truncated DHDPS (H225*), at 30°C, in 150 mM HEPES, pH 8.0, 0.16 mM NADPH, 50 microg/ml DHDPR
0.45
pyruvate
mutant K161A, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
0.556
pyruvate
-
recombinant mutant E84T, pH 8.0, temperature not specified in the publication
0.57
pyruvate
mutant K161R, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
0.64
pyruvate
-
recombinant mutant H56K, pH 8.0, temperature not specified in the publication
0.827
pyruvate
-
recombinant wild-type enzyme, pH 8.0, temperature not specified in the publication
0.85
pyruvate
by adding 2 mM (S)-aspartate 4-semialdehyde, at 60°C
1.5
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168/Asp171
1.7
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168
1.7
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168/Asp237
2.1
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168
2.4
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168/Asp171
2.6
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168/Asp237
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
kinetic study: the wild-type enzyme shows a ping pong mechanism, while the monomeric mutant L197D/Y107W shows ternary-complex mechanism
-
additional information
additional information
-
Michaelis-Menten kinetics for wild-type and mutant enzymes, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
35
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168
39
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp237
52
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168/Asp171
63
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp171/Arg237
68
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168/Asp237
88
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp237
97
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp171
108
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168/Asp171
111
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168
119
L-aspartate 4-semialdehyde
-
pH 8.0, 30°C, recombinant mutant A204R
134
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp171/Arg237
136
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 30°C, recombinant wild-type enzyme
138
L-aspartate 4-semialdehyde
-
pH 8.0, 30°C, recombinant wild-type enzyme
141
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168/Asp237
233
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp171
465
L-aspartate 4-semialdehyde
-
pH not specified in the publication, 45°C, recombinant wild-type enzyme
0.06
pyruvate
mutant K161A, at 30°C, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
0.16
pyruvate
mutant K161R, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
1.2
pyruvate
C-terminal truncated DHDPS (H225*), at 30°C, in 150 mM HEPES, pH 8.0, 0.16 mM NADPH, 50 microg/ml DHDPR
35
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168
39
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp237
45
pyruvate
wild-type, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
52
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168/Asp171
63
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp171/Arg237
68
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp168/Asp237
88
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp237
97
pyruvate
-
pH not specified in the publication, 30°C, recombinant mutant DELTAAsp171
108
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168/Asp171
111
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168
134
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp171/Arg237
136
pyruvate
-
pH not specified in the publication, 30°C, recombinant wild-type enzyme
141
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp168/Asp237
233
pyruvate
-
pH not specified in the publication, 45°C, recombinant mutant DELTAAsp171
465
pyruvate
-
pH not specified in the publication, 45°C, recombinant wild-type enzyme
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.26
L-aspartate 4-semialdehyde
mutant K161A, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
1.3
L-aspartate 4-semialdehyde
mutant K161R, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
110
L-aspartate 4-semialdehyde
-
pH 8.0, 30°C, recombinant mutant A204R
320
L-aspartate 4-semialdehyde
-
pH 8.0, 30°C, recombinant wild-type enzyme
380
L-aspartate 4-semialdehyde
wild-type, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
898
L-aspartate 4-semialdehyde
at 30°C, in 100 mM HEPES buffer, pH 8.0
0.13
pyruvate
mutant K161A, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
0.28
pyruvate
mutant K161R, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
300
pyruvate
wild-type, in 100 mM HEPES buffer, pH 8.0, 0.2 mM NADPH, 50 microg/ml DHDPR
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.63
(2E,5E)-4-oxohepta-2,5-dienedioic acid
more potent than the corresponding mono-ene inhibitors
0.15
(S)-aspartate-4-semialdehyde
pH and temperature not specified in the publication
0.21
3-hydroxy-2-oxopropanoate
time-dependent inhibition, value similar to that of (S)-lysine
0.33
dimethyl 2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
15% inhibition at 1 mM, binding with the active site lysine residue, kinetic analysis corresponds to slow-binding model of inhibition
0.33
dimethyl-(2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
-
pH 8.0, 30°C
0.04
dimethyl-2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetate)
-
pH 8.0, 30°C
0.19 - 0.57
pyruvate
pH and temperature not specified in the publication
2.96
2,2'-benzene-1,3-diylbis(oxoacetic acid)
49% inhibition at 5 mM, mimics the substrate pyruvate, binding with the active site lysine residue, slow inhibition
22
4-oxo-1,4-dihydropyridine-2,6-dicarboxylic acid
-
with respect to pyruvate
24.8
4-oxo-1,4-dihydropyridine-2,6-dicarboxylic acid
-
with respect to L-aspartate 4-semialdehyde
0.049
L-lysine
versus L-aspartate-4-semialdehyde, pH 8.0, 30°C, recombinant enzyme
0.18
L-lysine
mutant D193A, with respect to (S)-aspartate 4-semialdehyde
0.19
L-lysine
mutant Q196D, with respect to (S)-aspartate 4-semialdehyde
0.14
lysine
mutant K161R, with L-aspartate 4-semialdehyde as substrate
0.23
lysine
mutant K161A, with L-aspartate 4-semialdehyde as substrate
additional information
additional information
-
(S)-lysine allosteric inhibition kinetics and mechanism, overview
-
additional information
additional information
kinetic and thermodynamics of allosteric inhibitin by lysine, overview
-
additional information
additional information
-
kinetic and thermodynamics of allosteric inhibitin by lysine, overview
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
20
(2R,6S)-piperidine-2,6-dicarboxylic acid
Escherichia coli
-
IC50: 20 mM, 83% inhibition at 50 mM
22
4-oxo-1,4-dihydropyridine-2,6-dicarboxylic acid
Escherichia coli
-
i.e. chelidamic acid, IC50: 22 mM, 99% inhibition at 50 mM, uncompetitive inhibitor with respect to both substrates
14
dimethyl chelidamate
Escherichia coli
-
IC50: 14 mM. 99% inhibition at 50 mM, noncompetitive with respect to both substrates
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
1.5
Q81WN7
purified enzyme, recombinant enzyme in the absence of the substrate pyruvate
104
-
purified recombinant His-tagged enzyme, pH not specified in the publication, temperature not specified in the publication
12
Q81WN7
crude extract, recombinant enzyme in the presence of the substrate pyruvate
14.5
-
purified recombinant mutant L51K, pH 8.0, temperature not specified in the publication
174
purified recombinant His-tagged enzyme, coupled assay, pH and temperature not specified in the publication
19.2
-
purified recombinant mutant A49K, pH 8.0, temperature not specified in the publication
2
Q81WN7
crude extract, recombinant enzyme in the absence of the substrate pyruvate
33
Q81WN7
purified enzyme, recombinant enzyme in the presence of the substrate pyruvate
454.2
-
purified recombinant mutant H56K, pH 8.0, temperature not specified in the publication
478.1
-
purified recombinant mutant E84T, pH 8.0, temperature not specified in the publication
500.8
-
purified recombinant wild-type enzyme, pH 8.0, temperature not specified in the publication
559.4
-
purified recombinant mutant A49P, pH 8.0, temperature not specified in the publication
60.5
-
purified recombinant mutant L51T, pH 8.0, temperature not specified in the publication
81.6
-
purified recombinant mutant A49W, pH 8.0, temperature not specified in the publication
additional information
additional information
Q81WN7
DHDPS purified in the presence of pyruvate yields a greater amount of recombinant enzyme with 22fold greater specific activity compared with the enzyme purified in the absence of substrate
additional information
-
DHDPS purified in the presence of pyruvate yields a greater amount of recombinant enzyme with 22fold greater specific activity compared with the enzyme purified in the absence of substrate
additional information
specific activity relatively high even at 30°C, structural model reveals that the active site is well conserved
additional information
-
specific activity relatively high even at 30°C, structural model reveals that the active site is well conserved
additional information
structure in vicinity of the putative binding site for S-lysine indicates that the allosteric binding site in the Escherichia coli dihydrodipicolinate synthase does not exist in the enzyme of Corynebacterium glutamicum, difference of three non-conservative amino acids substitutions, explains lack of feedback inhibition by lysine in Corynebacterium glutamicum
additional information
-
structure in vicinity of the putative binding site for S-lysine indicates that the allosteric binding site in the Escherichia coli dihydrodipicolinate synthase does not exist in the enzyme of Corynebacterium glutamicum, difference of three non-conservative amino acids substitutions, explains lack of feedback inhibition by lysine in Corynebacterium glutamicum
additional information
attempt to examine the specificity of the active site of DHDPS, co-crystallization with the substrate analogue oxaloacetate, solution of the protein structure indicates that pyruvate rather than oxaloacetic acid bounds in the active site, decarboxylation of oxaloacetate not catalysed by DHDPS, rate of pyruvate production independent of DHDPS concentration, indicating that the decarboxylation of oxaloacetate is occurring by a spontaneous and enzyme-independent mechanism, confirmed by kinetic analysis
additional information
-
attempt to examine the specificity of the active site of DHDPS, co-crystallization with the substrate analogue oxaloacetate, solution of the protein structure indicates that pyruvate rather than oxaloacetic acid bounds in the active site, decarboxylation of oxaloacetate not catalysed by DHDPS, rate of pyruvate production independent of DHDPS concentration, indicating that the decarboxylation of oxaloacetate is occurring by a spontaneous and enzyme-independent mechanism, confirmed by kinetic analysis
additional information
role of beta-hydroxypruvate in regulating biosynthesis of dihydrodipicolinate unknown, crystal structure of DHDPS enzyme complexed with beta-hydroxypyruvate solved, active site shows the presence of the inhibitor covalently bound to Lys161, hydroxyl group of inhibitor is hydrogen-bonded to main-chain carbonyl of Ile203, evidence for a catalytic function played by this peptide unit, highly strained torsion angle conserved in active site of other homologous enzyme, points to critical role in catalysis
additional information
-
role of beta-hydroxypruvate in regulating biosynthesis of dihydrodipicolinate unknown, crystal structure of DHDPS enzyme complexed with beta-hydroxypyruvate solved, active site shows the presence of the inhibitor covalently bound to Lys161, hydroxyl group of inhibitor is hydrogen-bonded to main-chain carbonyl of Ile203, evidence for a catalytic function played by this peptide unit, highly strained torsion angle conserved in active site of other homologous enzyme, points to critical role in catalysis
additional information
role of Tyr107 residue in determining the quaternary structure, structural, biophysical, and kinetic studies of the Y107W mutant, catalytic ability and apparent melting temperature reduced by the mutation, tetrameric quaternary structure critical to control specificity, heat stability, and intrinsic activity
additional information
substrate protection experiments, inhibition by alkylation the active-site lysine residue (Lys161) and a surface cysteine residue, slower alkylation of other cysteine residues with lower surface accessibility, co-incubation of the enzyme with the inhibitors in the presence of pyruvate protect against active-site alkylation and cysteine residues
additional information
analysis of ability of rhizopines to interact with MosA protein in the presence and absence of methyl donors, no methyltransferase activity observed in the presence of scyllo-inosamine and S-adenosylmethionine (SAM), presence of rhizopine compounds does not affect kinetics of dihydrodipicolinate synthesis
additional information
titration of (S)-lysine into buffered solutions of MosA protein in the presence or absence of saturating amounts of pyruvate, thermodynamic data for (S)-Lysine binding to MosA protein, non-competitive mechanism with substrate-dependent differences in the energetics of inhibitor binding
additional information
archetypal subunit orientation in the crystal structure of other dihydrodipicolinate synthase enzymes not observed, structure refinement will provide information regarding the structural evolution of dihydrodipicolinate synthase and the design of antibiotics targeting lysine biosynthesis in Staphylococcus aureus
additional information
-
archetypal subunit orientation in the crystal structure of other dihydrodipicolinate synthase enzymes not observed, structure refinement will provide information regarding the structural evolution of dihydrodipicolinate synthase and the design of antibiotics targeting lysine biosynthesis in Staphylococcus aureus
additional information
mechanistic insight into catalysis, structural features and the evolution of quarternary structure, MRSA-DHDPS enzyme exists in a monomer-dimer equilibrium in solution, MRSA-DHDPS dimer is catalytically active
additional information
-
mechanistic insight into catalysis, structural features and the evolution of quarternary structure, MRSA-DHDPS enzyme exists in a monomer-dimer equilibrium in solution, MRSA-DHDPS dimer is catalytically active
additional information
quaternary structure different from other characterized homologues, dimer both in solution and in the crystal, catalytically important Lys-163 and the proton relay catalytic triad comprising Thr-46, Tyr-109 and Tyr-135 corresponds well with the enzyme homologue of Escherichia coli, deletion mutant lacking the three helical domains reveals a significant reduction in enzymatic activity, changes in the catalytic site upon pyruvate binding provide a structural basis for the ping-pong reaction mechanism, no feedback inhibition by lysine, free and substrate bound forms provide a structural rationale for catalytic mechanism, unique conformational features crucial for the design of specific non-competitive inhibitors
additional information
-
quaternary structure different from other characterized homologues, dimer both in solution and in the crystal, catalytically important Lys-163 and the proton relay catalytic triad comprising Thr-46, Tyr-109 and Tyr-135 corresponds well with the enzyme homologue of Escherichia coli, deletion mutant lacking the three helical domains reveals a significant reduction in enzymatic activity, changes in the catalytic site upon pyruvate binding provide a structural basis for the ping-pong reaction mechanism, no feedback inhibition by lysine, free and substrate bound forms provide a structural rationale for catalytic mechanism, unique conformational features crucial for the design of specific non-competitive inhibitors
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.6
assay at, measured using a coupled assay with lactate dehydrogenase to detect pyruvate production
8
specific condensation of pyruvate and (S)-aspartate 4-semialdehyde optimally at
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
85
specific condensation of pyruvate and (S)-aspartate 4-semialdehyde optimally at, assay performed at 60°C, structural model reveals that the active site is well conserved
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Agrobacterium tumefaciens C58 / ATCC 33970
DSM 15242T, JCM11007
SwissProt
brenda
Escherichia coli LATR11
strain LATR11 is derived from the wild-type strain Escherichia coli MG1655
UniProt
brenda
four isozymes, MtDHDPS, MtDHDPS2, MtDHDPS3, and MtDHDPS4
-
-
brenda
methicillin-resistent MRSA252 strain
SwissProt
brenda
strain LATR11 is derived from the wild-type strain Escherichia coli MG1655
UniProt
brenda
potato, increased levels in transgenic plants containing the Escherichia coli gene
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
isozymes MtDHDPS1, MtDHDPS3, and MtDHDPS4 shows highest expression in mature seeds
brenda
-
isozymes MtDHDPS1, MtDHDPS3, and MtDHDPS4 shows highest expression in mature seeds
-
brenda
-
highest activities are observed at 16 and 20 days after pollination, followed by a major decline at 24 days after pollination
brenda
additional information
-
organ-specific isozyme expression
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
enzyme mutants with deleted dapA gene are viable and able to grow in a mouse lung infection model
malfunction
-
the FaDHDPS1 deletion mutant is defective in conidiation, virulence and deoxynivalenol biosynthesis. In addition, deletion of FaDHDPS1 results in tolerance to sodium pyruvate, lysine, low temperature and Congo red
metabolism
-
sequential production of dihydrodipicolinate and dipicolinic acid appears to be catalysed by DHDPA synthase followed by an electron transfer flavoprotein, EtfA from Clostridium perfringens. Spontaneous dipicolinic acid formation in the presence of high concentrations of DapA
metabolism
-
DHDPS is an oligomeric enzyme that catalyzes the first committed step of the lysine biosynthesis pathway in plants and bacteria, which yields essential building blocks for cell-wall and protein synthesis
metabolism
first enzyme unique to the diaminopimelate pathway of lysine biosynthesis
metabolism
-
dihydrodipicolinate synthase is a key enzyme in the lysine biosynthesis pathway that catalyzes the condensation of pyruvate and aspartate semi-aldehyde
metabolism
-
feedback regulation of the enzyme is directly correlated to L-lysine production
metabolism
-
lysine biosynthesis in plants is tightly regulated by feedback inhibition of the end product on dihydrodipicolinate synthase, the first enzyme of the lysine-specific branch
metabolism
lysine biosynthesis in plants is tightly regulated by feedback inhibition of the end product on dihydrodipicolinate synthase, the first enzyme of the lysine-specific branch
metabolism
the enzyme catalyses the first committed step in the lysine biosynthesis pathway, the condensation of pyruvate and (S)-aspartate semialdehyde to form (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid
metabolism
-
the enzyme catalyses the first committed step in the lysine biosynthesis pathway, the condensation of pyruvate and (S)-aspartate semialdehyde to form (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid
metabolism
the enzyme catalyses the first committed step in the lysine biosynthesis pathway, the condensation of pyruvate and (S)-aspartate semialdehyde to form (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid
metabolism
the enzyme catalyses the first committed step in the lysine biosynthesis pathway, the condensation of pyruvate and (S)-aspartate semialdehyde to form (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid
metabolism
the enzyme catalyses the first committed step in the lysine biosynthesis pathway, the condensation of pyruvate and (S)-aspartate semialdehyde to form (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid
metabolism
the enzyme catalyzes the branch-point reaction in the biosynthetic pathway leading to meso-diaminopimelate and (S)-lysine in plants and bacteria: condensation of (S)-aspartate-4-semialdehyde and pyruvate to form (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid. There are four variants of the meso-diaminopimelate/(S)-lysine pathway, they all share the same enzymatic steps for the synthesis of tetrahydrodipicolinate from aspartate, which includes the reaction catalyzed by the enzyme, overview
metabolism
the enzyme catalyzes the first step in the diaminopimelic acid pathway of lysine biosynthesis
metabolism
-
the enzyme catalyzes a step of the diaminopimelate biosynthetic pathway of lysine
metabolism
the enzyme catalyzes a step of the diaminopimelate biosynthetic pathway of lysine
metabolism
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
metabolism
the enzyme catalyzes the first committed step in the diaminopimelate pathway
metabolism
the enzyme catalyzes the first committed step in the lysine biosynthesis pathway of plants
metabolism
-
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
-
metabolism
-
DHDPS is an oligomeric enzyme that catalyzes the first committed step of the lysine biosynthesis pathway in plants and bacteria, which yields essential building blocks for cell-wall and protein synthesis
-
metabolism
-
the enzyme catalyzes a step of the diaminopimelate biosynthetic pathway of lysine
-
metabolism
-
the enzyme catalyzes the committed step in the synthesis of diaminopimelate and lysine to facilitate peptidoglycan and protein synthesis
-
metabolism
Agrobacterium tumefaciens C58 / ATCC 33970
-
the enzyme catalyses the first committed step in the lysine biosynthesis pathway, the condensation of pyruvate and (S)-aspartate semialdehyde to form (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid
-
metabolism
Agrobacterium tumefaciens C58 / ATCC 33970
-
the enzyme catalyses the first committed step in the lysine biosynthesis pathway, the condensation of pyruvate and (S)-aspartate semialdehyde to form (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid
-
metabolism
-
feedback regulation of the enzyme is directly correlated to L-lysine production
-
metabolism
-
the enzyme catalyzes the first committed step in the diaminopimelate pathway
-
metabolism
-
lysine biosynthesis in plants is tightly regulated by feedback inhibition of the end product on dihydrodipicolinate synthase, the first enzyme of the lysine-specific branch
-
physiological function
complementation of the auxotrophy of Escherichia coli XL1-Blue KanRDELTAdapA cells only with the plasmid pUCX:dapA encoding wild-type DHDPS
physiological function
DHDPS can recover the DHDPS-deleted mutant of Escherichia coli
physiological function
-
DHDPS catalyses a branch point reaction the condensation of pyruvate and (S)-aspartate beta-semialdehyde to form an unstable product, (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, which is ultimately advanced to the final metabolites (S)-lysine and meso-diaminopimelate
physiological function
the enzyme catalyzes a rate-limiting step in the (S)-lysine biosynthetic pathway, which is regulated by a feedback mechanism through lysine
physiological function
-
FaDHDPS1 plays an important role in the regulation of vegetative differentiation, pathogenesis and adaption to multiple stresses in Fusarium asiaticum. It is involved in diverse cellular processes in filamentous fungi Fusarium asiaticum, including conidiation, conidial germination, cell wall pressure response, low temperature tolerance, carbon/nitrogen sources utilization, secondary metabolism and virulence
physiological function
-
the enzyme catalyzes a step in the pathway for the biosynthesis of L-lysine
physiological function
-
the enzyme catalyzes a step in the pathway for the biosynthesis of L-lysine
-
additional information
-
monomeric species exhibit an enhanced propensity for aggregation and inactivation, indicating that whilst the oligomerization is not an intrinsic criterion for catalysis, higher oligomeric forms may benefit from both increased catalytic efficiency and diminished aggregation propensity
additional information
-
pyruvate binding occurs near the large interface of DHDPS, and is likely, therefore, to stabilize this solvent-accessible face, which favors the formation of a dimer rather than a monomer. For the DELTAAsp168/Arg237 and DELTAAsp168/Asp171 DHDPS variants addition of pyruvate shifts the equilibrium from primarily monomer to favor almost exclusively dimers. On the other hand, for the DELTAAsp168 DHDPS variant, the monomer-tetramer equilibrium shifts from primarily monomer to primarily tetramer on addition of pyruvate
additional information
-
the tetrameric structure is not essential for activity in DHDPS from Mycobacterium tuberculosis
additional information
-
optimal activity is achieved by minimizing the inherent dimer flexibility using buttressing two dimers together in the case of the Escherichia coli tetrameric enzyme, active site structure simulations, overview
additional information
-
optimal activity is achieved by minimizing the inherent dimer flexibility using strengthening and extending the dimer interface in the dimeric Staphylococcus aurus MRSA strain enzyme, active site structure simulations, overview
additional information
-
structure comparison with the enzyme from Corynebacterium glutamicum
additional information
-
structure comparison with the enzyme from Escherichia coli
additional information
structure-based sequence alignments, based on the DapA crystal structure, reveal the presence of two homologues, PA0223 and PA4188, in Pseudomonas aeruginosa that can substitute for DapA in the PAO1DELTAdapA mutant. In vitro experiments using recombinant PA0223 protein do not detect any DapA activity
additional information
-
structure-based sequence alignments, based on the DapA crystal structure, reveal the presence of two homologues, PA0223 and PA4188, in Pseudomonas aeruginosa that can substitute for DapA in the PAO1DELTAdapA mutant. In vitro experiments using recombinant PA0223 protein do not detect any DapA activity
additional information
the catalytic site of DHDPS is situated at the C-terminal end of the TIM barrel where the pyruvate-binding residue, Lys161, lies in a solvent-accessible cleft with Arg138 capping the binding site. One-half of the active site is blocked by binding interactions of another monomer
additional information
-
the catalytic site of DHDPS is situated at the C-terminal end of the TIM barrel where the pyruvate-binding residue, Lys161, lies in a solvent-accessible cleft with Arg138 capping the binding site. One-half of the active site is blocked by binding interactions of another monomer
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
-
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
additional information
the enzyme has unique disulfide linkage which is critical for the stability of the enzyme tetramer, but is not conserved in homologous enzymes, molecular dynamics simulation of the native structure of the enzyme tetramer and dimeric units containing complexes of enzyme-pyruvate or enzyme-lysine, enzyme structure comparisons and ligand docking analysis, overview
additional information
-
the enzyme has unique disulfide linkage which is critical for the stability of the enzyme tetramer, but is not conserved in homologous enzymes, molecular dynamics simulation of the native structure of the enzyme tetramer and dimeric units containing complexes of enzyme-pyruvate or enzyme-lysine, enzyme structure comparisons and ligand docking analysis, overview
additional information
-
structure comparison with the enzyme from Escherichia coli
-
additional information
Agrobacterium tumefaciens C58 / ATCC 33970
-
the catalytic triad, consisting of Tyr133, Thr44, and Tyr107, acts as a proton relay to transfer protons to and from the active site via a water-filled channel leading to bulk solvent
-
additional information
-
structure comparison with the enzyme from Corynebacterium glutamicum
-
Show AA Sequence and Transmembrane Helices (50359 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
123000
124000
125300
tetramer size of wild-type protein, mass spectrometry, mutant form Y107W reveals a mixture of primarily monomer and tetramer in solution
130000
134000
-
calculation from sedimentation and diffusion coefficient, Stokes' radius
150000
native protein, gel filtration
158000
native protein, gel filtration, homotetramer predicted
31000
34000
62400
72000
-
4 * 37000-38000 + x * 72000, the 72000 Da subunit possibly modifies the structure and kinetic properties, SDS-PAGE
73000
approximating the size of two DHDPS proteins interacting to form a dimer
34000
size of monomer inccluding His-tag, calculated from sequence
34000
-
4 * 34000, SDS-PAGE, role of quaternary structure in the TIM-barrel family of enzymes, overview. Unlike other DHDPS enzymes, but like many thermophilic enzymes, Tm-DHDPS has a large number of charged residues at the quaternary interface. Removal of electrostatic interactions disrupts quaternary structure
62400
-
4 * 62400, crystal structure, the tetrameric structure is not essential for activity in DHDPS from Mycobacterium tuberculosis
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
homotetramer
tetramer
additional information
dimer
three-dimensional structure determination shows that DHDPS forms a homodimer which is stabilized by several hydrogen bonds and van der Waals forces at the interface, active site structure, overview. Each monomer is composed of two domains, the N-terminal domain consists of residues 1-224, and forms an 8-fold parallel alpha/beta barrel
homodimer
in solution and in the crystal, gel filtration, crystallization and dynamic light scattering experiments
homodimer
-
in solution and in the crystal, gel filtration, crystallization and dynamic light scattering experiments
-
homotetramer
the enzyme adopts the canonical homotetrameric structure in both solution and the crystal state
homotetramer
Agrobacterium tumefaciens C58 / ATCC 33970
-
the enzyme adopts the canonical homotetrameric structure in both solution and the crystal state
-
homotetramer
ribbons rendition of homotetramer in the crystal lattice shown
homotetramer
wild-type, mixture of primarily monomer and tetramer in solution determined for mutant form Y107W, hydrodynamic properties of Y107W oligomers calculated by sedimentation velocity analyses
homotetramer
the enzyme shows the typical homotetrameric form exhibited by bacterial DHDPS enzymes, present as a dimer of tight dimers. Each monomer consists of an N-terminal domain (residues 1-224) showing a parallel (beta/alpha)8-barrel (TIM barrel) motif. The smaller C-terminal domain, residues 224-292, is comprised of three alpha-helices
homotetramer
homotetramer of four identical (beta/alpha)8-barrel monomers, a dimer of tight dimers, with two tight-dimers binding in a head-to-head manner, with the active site situated near the center of the barrel, molecular dynamics simulations
tetramer
the overall quaternary structure of the enzyme consists of four crystallographically independent molecules (A, C, D, and E) forming dimer of dimers. The monomer exhibits a TIM barrel fold and comprises of 11 alpha helices built by 146 amino acids out of which the first 8 helices form the TIM barrel domain and remaining three helices present in the C-terminal. The monomer also has 10 beta strands composed of 42 amino acids. The enzyme molecule has two types of dimer interfaces, weak-dimer interface and tight-dimer interfaces, structure model, overview
tetramer
similar to oligomeric states of other homologous enzyme
tetramer
homotetramer of (alpha/beta)8 barrels, each containing one active site, crystal structure
tetramer
the dimer-dimer interface is small, accounts only 4.3% of the subunit surface area
tetramer
-
4 * 62400, crystal structure, the tetrameric structure is not essential for activity in DHDPS from Mycobacterium tuberculosis
tetramer
-
4 * 34000, SDS-PAGE, role of quaternary structure in the TIM-barrel family of enzymes, overview. Unlike other DHDPS enzymes, but like many thermophilic enzymes, Tm-DHDPS has a large number of charged residues at the quaternary interface. Removal of electrostatic interactions disrupts quaternary structure
tetramer
-
4 * 37000-38000 + x * 72000, the 72000 Da subunit possibly modifies the structure and kinetic properties, SDS-PAGE
additional information
Q81WN7
the tetramer-dimer dissociation constant of the enzyme is 3fold tighter in the presence of pyruvate compared with the apo form
additional information
-
the tetramer-dimer dissociation constant of the enzyme is 3fold tighter in the presence of pyruvate compared with the apo form
additional information
-
the tetramer-dimer dissociation constant of the enzyme is 3fold tighter in the presence of pyruvate compared with the apo form
-
additional information
-
disruption of quaternary structure of DHDPS generates a functional monomer that is no longer inhibited by lysine, overview
additional information
-
flexibility and its relationship to quaternary structure and function from molecular dynamic simulations of native tetrameric and mutant dimeric enzyme forms, it shows that the mutant dimeric enzyme form displays high flexibility, resulting in monomer reorientation within the dimer and increased flexibility at the tight-dimer interface, whereas the enzyme tetramer is relatively rigid. The enzyme dimer exhibits disorder within its active site with deformation of critical catalytic residues and removal of key hydrogen bonds that render it inactive
additional information
the recombinant enzyme adopts a characteristic alpha/beta conformation which is retained up to 65°C
additional information
-
the recombinant enzyme adopts a characteristic alpha/beta conformation which is retained up to 65°C
additional information
-
flexibility and its relationship to quaternary structure and function from molecular dynamic simulations show that the native dimeric enzyme form from a methicillin-resistant strain displays high flexibility, resulting in monomer reorientation within the dimer and increased flexibility at the tight-dimer interface and maintains its catalytic geometry and is thus fully functional
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure analysis, PDB ID 2HMC, structure comparisons
crystal structure analysis, PDB ID 2R8Wm, structure comparisons
crystal structure analysis, PDB ID 3B4U, structure comparisons
crystal structure analysis, PDB IDs 4I7U, 4I7V, and 4I7W, resolution at 1.42-1.69 A, structure comparisons
purified recombinant His-tagged enzyme in the unliganded form and in forms with bound substrate and with bound substrate plus allosteric inhibitor lysine, hanging drop vapour diffusion method, mixing of 0.002 ml of 10 mg/ml protein in 20 mM Tris, pH 8.0, with 0.002 ml of reservoir solution containing 0.1 M Tris, pH 8.5, and 2 M ammonium sulfate, for ligand-bound enzyme from 0.17 M lithium sulfate monohydrate, 0.085 M Tris pH 8.5, 25.5%(w/v) PEG 4000, 15%(v/v) glycerol with addition of 20 mM pyruvate or 20 mM pyruvate and 20 mM lysine, equilibration against 1 ml reservoir solution, 20°C, overnight, X-ray diffraction structure determination and analysis at 1.40-1.55 A resolution
purified recombinant enzyme, sitting drop vapour diffusion method, mixing of 0.001 ml of 21.8 mg/ml protein in 20 mM Tris-HCl at pH 8.0 and 0.2 M NaCl, with 0.001 ml of reservoir solution containing 4 M sodium phosphate, 0.1 M imidazole, and 0.2 M NaCl at pH 8.0, 18°C, 1 week, X-ray diffraction structure determination and analysis at 1.90 A resolution, molecular replacement
purified recombinant His-tagged enzyme, sitting drop vapour diffusion method, 0.0015 ml of 14.5 mg/ml protein in 20 mM Tris-HCl, pH 8.0 is mixed with 0.0015 ml of reservoir solution containing 20% w/v PEG 6000, 200 mM sodium chloride, 100 mM Tris-HCl, pH 8.0, including 0.02% w/v sodium azide, 20°C, method screening, 5 days to 8 weeks, X-ray diffraction structure determination and analysis at 2.5 A resolution
in complex with pyruvate, by sitting- and hanging-drop vapor diffusion method, to 2.15 A resolution, shares the same space group, unit cell parameters, and a similar resolution to the structure of substrate unbound DHDPS. Twelve more hydrogen bond interactions at both interfaces in the crystal structure of pyruvate-bound DHDPS relative to the apo structure
Q81WN7
in the presence of pyruvate, the hanging-drop vapour-diffusion method, at a resolution of 2.15 A. Crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 84.5, b = 124.6, c = 131.0 A, beta = 90.0
Q81WN7
sitting-drop vapor-diffusion, protein crystals are grown in conditions consisting of 20%(w/v) PEG 4000, 100 mM sodium citrate tribasic pH 5.5 and diffract to 2.10 A resolution. They belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 79.96, b = 106.33, c = 136.25 A
crystals are grown in a solution of 0.28 M sodium acetate, 30% PEG 4000, 0.1 M TRIS pH 8.5 using the hanging drop vapor diffusion method
-
crystallized in a number of forms, predominantly using PEG precipitants, estimated solvent content of 41%, best crystal diffracting to beyond 1.9 A resolution
-
in the presence of its substrate pyruvate, by the sitting-drop vapour diffusion method, to 1.2 A resolution. Belongs to space group C2, in contrast to the unbound form, which has trigonal symmetry. Unit-cell parameters are a = 143.4, b = 54.8, c = 94.3 A , beta = 126.3. The crystal volume per protein weight is 2.3 A3 Da-1 (based on the presence of two monomers in the asymmetric unit), with an estimated solvent content of 46%
-
hanging drop method, data collection and refinement statistics, refinement resolution originally extended to 3.0 A, gradually increased to 2.5 A, and finally to 2.2 A, structural similarities to other dihydrodipicolinate synthase
by the hanging drop-vapour diffusion method, mutants K161A and K161R solved at resolutions of 2.0 and 2.1 A, respectively. They show no changes in their secondary or tertiary structures when compared to the wild-type structure. Crystal structure of mutant K161A with pyruvate bound at the active site solved at a resolution of 2.3 A, reveals a defined binding pocket for pyruvate that is thus not dependent upon lysine 161
complexed with pyruvate, the substrate analogs succinate alpha-semialdehyde and alpa-ketopimelic acid, the inhibitor dipicolinic acid, and the natural feedback inhibitor L-lysine, hanging drop vapor diffusion method, in the presence of beta-octyl glucoside using either potassium phosphate buffer (pH 10) or potassium citrate buffer (pH 7.0) as the precipitant
crystal structure of mutant enzyme R138H and R138A, hanging-drop vapor diffusion method
examination of the specificity of the active site of DHDPS, co-crystallization with the substrate analogue oxaloacetate, data-collection and refinement statistics
hanging-drop vapour-diffusion method, crystal struture of native and (S)-lysine-bound dihydropicolinate synthase are presented to 1.9 A and 2.0 A resolution, respectively
in complex with beta-hydroxypyruvate, hanging drop vapor-diffusion method, data processing and refinement statistics
mutant T44S, crystals are isomorphous to those of the wild-type enzyme, no significant modification in its tertiary or quaternary structure from that of the wild-type enzyme
mutant Y107W, hanging-drop vapor diffusion method, diffraction to beyond 2.0 A resolution, data collection and refinement statistics, solid-state structure of the mutant enzyme largely unchanged
purified enzyme in complex with pyruvate and substrate analogue succinic acid semialdehyde, hanging drop vapor diffusion method, mixing of 0.003 ml of 8 mg/mL protein in 20 mM Tris-HCl, pH 8.0, with 0.0012 ml of precipitant solution containing 1.8 M K2HPO4, pH 10, and 0.0006 ml of N-octyl-beta-R-glucopyranoside 6% w/v, 4°C, 3-4 days, soaking in cryoprotectant solution containing 1.8 M K2HPO4, pH 10, glycerol 20% v/v, and 120 mM succinic acid semialdehyde and 40 mM pyruvate, X-ray diffraction structure determination and analysis at 2.3 A resolution
purified recombinant wild-type and mutant enzymes, hanging or sitting drop vapour diffusion method, at 4°C and 21°C, 0.006 ml protein solutions: about 10 mg/ml protein, 1.8 M K2PO4, pH 10.0, N-octyl-beta-R-glucopyranoside 6% w/v, + 2 ml reservoir solution: 1.8 M K2PO4, pH 10.0, 3-4 days, X-ray diffraction structure determination and analysis at 2.35-2.5 A resolution
at 239K using the hanging drop-vapor diffusion method, at 1.5 A resolution. The four subunits of the asymmetric unit assemble to form a tetramer with an approximate 222 symmetry. At the active site, three residues Tyr132, Thr43 and Tyr106 are observed to constitute a catalytic triad. Has a unique extensive dimerdimer interface that is mediated by strong hydrophobic interactions supplemented by two sets of three hydrogen bonds between four polar residues. Belongs to space group P2(1)2(1)2(1) with cell parameters a = 67.03 A, b = 120.52 A, c = 161.1 A
purified recombinant enzyme, hanging drop vapour diffusion method, mixing of 0.002 ml of 11 mg/ml protein in 20 mM Tris, pH 7.5, with 0.002 ml of reservoir solution containing 0.2 M magnesium chloride, 10% w/v PEG 8000, 0.1 M Tris chloride, pH 10, at 8°C, X-ray diffraction structure determination and analysis at 1.65-1.74 A resolution, molecular replacement
-
by the oil-batch method at 291 K, to 2.2 A resolution. Belongs to space group P21 with unit-cell parameters a = 80.5 A, b = 76.5 A, c = 101.9 A, gamma = 106.9 A. The asymmetric unit contains four DHDPS molecules, forming a homotetramer with approximate 222 symmetry. The overall tertiary structure of DHDPS possesses a (beta/alpha)8-barrel fold (TIM barrel) with three additional alpha-helices (alpha9-alpha11) at the C-terminus of the chain. The beta-strands of the barrel form an intrinsic network of hydrogen-bonding interactions with the neighbouring beta-strands and are oriented in the same directions. The functional residue Lys161, which participates in Schiff-base formation, is located within the beta-barrel and the side chain of Tyr132 sits over this residue
hanging-drop vapour-diffusion method, crystallizes in a monoclinic crystal form
-
micro-batch method and hanging drop vapour diffusion methods of crystallization
purified recombinant DHDPS mutant A204R, sitting drop vapour diffusion method at room temperature, 200 nl of 10 mg/ml protein in 20 mM Tris-HCl, 2 mM 2-mercaptoethanol, 250 mM NaCl, 5% v/v glycerol, 10 mM pyruvate, pH 8.0, is mixed with 230 nl reservoir solution containing 2.0 M ammonium sulphate, 100 mM sodium acetate, pH 5.5, X-ray diffraction structure determination and analysis at 2.0 A resolution
-
three-dimensional structure is determined and refined at 2.28 A resolution
to 2.0 A resolution, space group of the crystal is P212121, with unit cell dimensions of a = 80.7, b = 115.7 and c = 132.1 A. The secondary and tertiary structures are remarkably similar to that of Escherichia coli DHDPS. The hydrogen bond lengths within the catalytic triad, and particularly that between Y133 and T44, differ significantly from those of the Escherichia coli enzyme
purified recombinant DHDPS, free or in complex with inhibitor (S)-lysine, 15 mg/ml protein in 50 mM Tris-HCl, pH 8.5, at 20°C using hanging drop vapour diffusion method, mixing of 0.005 ml protein solution with 0.005 ml well solution containing 30% w/v PEG-3350, 170 mM MgCl2, 70 mM Tris-HCl, pH 8.5, and 6% v/v propylene glycol. Crystals obtained without 6% propylene glycol are soaked in the reservoir containing 20 mg/ml (S)-lysine, X-ray diffraction structure determination and analysis at 2.65-2.85 A resolution
purified recombinant His6-tagged enzyme, hanging drop vapour diffusion method, mixing of 0.002 m of 12.5 mg/ml protein solution with 0.002 ml of reservoir solution containing 18% of PEG6000, 0.2 M MgCl2, and 0.1 M TRIS-HCl, pH 7.6, X-ray diffraction structure determination and analysis at 1.6 A resolution, molecular replacement
purified recombinant His-tagged enzyme, hanging-drop vapour-diffusion method, 7.6 mg/ml protein in 150 nl solution is mixed with 150 nl of reservoir solution containing 200 mM ammonium sulfate, 100 mM Bis-Tris pH 5.0-6.0, 23-26% w/v PEG 3350, 0.02% w/v sodium azide, X-ray diffraction structure determination and analysis at 2.5 A resolution
-
crystallization conditions are optimized using vapour diffusion in hanging drops at room temperature. Crystal grown in the presence of pyruvate diffracted X-rays to 2.3 A resolution using synchrotron radiation and belonged to the orthorhombic space group C222(1), with unit-cell parameters a = 69.14, b = 138.87, c = 124.13 A
-
structure of MosA protein solved to 1.95 A resolution, data collection and refinement statistics
atomic resolution at 1.45 A, crystal structure confirms the dimeric quarternary structure, reveals that the dimerization interface of the MRSA-DHDPS enzyme is more extensive in buried surface area and noncovalent contacts than the equivalent interface in tetrameric DHDPS enzymes from other bacterial species
hanging-drop and sitting-drop method, solved in the native form and in complex with pyruvate at 2.3 A and 2.2 A resolution, respectively, single crystal grown in 2 M ammonium sulfate and 0.1 M Bis-Tris pH 6.5 used for data collection, processing and refinement statistics
X-ray data-collection statistics, best crystal diffracting to beyond 1.45 A resolution
by the hanging-drop vapour-diffusion method, to 2.1 A resolution. The crystal belongs to space group P42212, with unit-cell parameters a = b = 105.5, c = 62.4 A, but the R factors remain high following initial processing of the data. The data set is twinned and it is thus reprocessed in space group P2, resulting in a significant reduction in the R factors
-
purified recombinant Tm-DHDPS-DELTAArg-237, vapor diffusion method, mixing of 150 nl protein solution, containing 11.2 mg/ml protein in 20 mM Tris-HCl, pH 8.0, with 150 nl reservoir solution, containing 40% v/v PEG 300, 100 mM phosphate-citrate, buffer, pH 4.2, and 0.02% w/v sodium azide, X-ray diffraction structure determination and analysis at 1.9-2.1 A resolution
-
purifed recombinant detagged enzyme in complex with pyruvate, hanging drop vapour diffusion method, mixing of 0.002 ml of 10 mg/ml protein in 20 mM Tris, 150 mM NaCl, pH 8.0, and 20 mM pyruvate, with 0.002 ml of reservoir solution containing 0.1 M Bis-Tris propane, pH 8.2, 0.2 M sodium bromide, and 20% w/v PEG 3350, equilibration against 1 ml of reservoir solution, 20°C, method ooptimization, X-ray diffraction structure determination and analysis at 2.2 A resolution
-
purified recombinant His-tagged enzyme, hanging drop vapor diffusion method, mixing of 0.002 ml of protein in 20 mM pyruvate and 20 mM lysine, with 0.002 ml of reservoir solution containing 0.1 M MES, pH 6.5, 6% v/v PEG 20000, X-ray diffraction structure determination and analysis at 2.40 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
L170E/G191E
K68H
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
P61A/T63L
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
P61A/T63L/A65H
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
T63L
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
T92E
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
T96E
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine and shows reduced activity compared to the wild-type enzyme
T96E/K68H
-
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
-
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
-
site-directed mutagenesis the mutant is activated by L-lysine 5fold shows reduced activity compared to the wild-type enzyme
T96E/K68H/T63L
-
site-directed mutagenesis, the mutant is activated by L-lysine and shows reduced activity compared to the wild-type enzyme
K68H
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
-
P61A/T63L
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
-
T63L
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
-
T92E
-
site-directed mutagenesis, the mutant is not inhibited by L-lysine
-
A49K
-
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
A49P
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme and is still sensitive to L-lysine
A49W
-
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
-
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
-
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
-
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
L51T
-
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
-
mutant enzyme H56K is more conducive to L-lysine production than mutant H118Y
-
H56K
Escherichia coli LATR11
-
mutant enzyme H56K is more conducive to L-lysine production than mutant H118Y
-
A49P
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme and is still sensitive to L-lysine
-
E84T
-
site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme and is insensitive to L-lysine
-
H56K
-
site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme and is insensitive to L-lysine
-
L51T
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme and is sill sensitive to L-lysine
-
A204R
-
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
L170E/G191E
Q81WN7
dimeric mutant of the enzyme, retains only 1.8% of the total catalytic activity of the wild-type tetrameric enzyme
L170E/G191E
-
dimeric mutant of the enzyme, retains only 1.8% of the total catalytic activity of the wild-type tetrameric enzyme
-
H56K
-
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
K161A
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
Y107F
site-directed mutagenesis, reduced activity, structure is similar to the wild-type enzyme
additional information
-
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
-
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
detailed structural properties of the mutant enzymes based on the crystal structure models
additional information
-
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
-
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
-
disruption of quaternary structure of DHDPS generates a functional monomer that is no longer inhibited by lysine, overview
additional information
-
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
-
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
-
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
-
mutant construction by gene replacement of gene dapA (PA1010) via the sacB-based strategy
additional information
-
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
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50 - 60
Q81WN7
thermostability is significantly enhanced in the presence of the substrate pyruvate
59.8
Q81WN7
is thermally stabilised by the first substrate, pyruvate, to a greater extent than its Escherichia coli counterpart
60
65
the recombinant enzyme adopts a characteristic alpha/beta conformation which is retained up to 65°C
74 - 79
-
inactivation energy: 117000 cal/mol, change in free energy, DELTAF: 23400 cal/mol, change in enthalpy, DELTAH: 113500 cal/mol, change in entropy DELTAS: 259 cal/degre e/mol
80
-
no reactivation after heating to 80°C, pyruvate increases thermostability
90
60
-
inactivation energy: 67300 cal/mol, change in free energy, DELTAF: 22500 cal/mol, change in enthalpy, DELTAH: 66700 cal/mol, change in entropy DELTAS: 133 cal/degree/mol
90
the enzyme is stable up to, high-temperature molecular dynamics simulation of the wild-type and mutant enzymes
90
7 h, 40% loss of activity. When the enzyme is incubated at 90°C in 8M urea, 60% of the activity is lost after 90 min
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
NaCl required for stability, the amount is inversely proportional to the protein concentration
-
the secondary and quaternary structure is significantly stabilized in the presence of pyruvate
Q81WN7
unstable at all stages of purification, not stabilized by dithioerythritol, glycerol, KCl, (NH4)2SO4, sucrose, divalent cations
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 0.06 M phosphate buffer, pH 7.5, 3 months, no loss of activity
-
-20°C, 10 mM triethanolamine buffer, pH 7.5, 10 mM 2-mercaptoethanol, stable for at least 6 months
-
-20C, 20 mM Tris-HCl buffer, pH 8.0
4°C, 20 mM bis-Tris propane buffer, pH 8.0, 10 mM pyruvate, 300 mM NaCl, 0.01% NaN3, 3 weeks, 20% loss of activity
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by anion-exchange chromatography, hydrophobic interaction and gel filtration
-
by centrifugation and gel filtration
by centrifugation, anion-exchange liquid chromatography and gel filtration, 2fold, more than 95% pure
-
by gel filtration, recombinant enzyme in the absence of the substrate pyruvate (with a yield of 36.3%) and presence of the substrate pyruvate (with a yield of 98%)
Q81WN7
by sonication, anion-exchange and hydrophobic interaction liquid chromatography
Q81WN7
gel filtration
gel filtration, SDS-PAGE
mutant T44S, no pyruvate added to the crude extract prior to sonication, purified by heat shock and ion-exchange chromatography, 20.7fold with a yield of 123%
partial
recombinant enzyme from Escherichia coli strain BL21(DE3) by anion exchange and hydrophobic interaction chromatography, followed by dialysis
-
recombinant enzyme from Escherichia coli strain BL21-CodonPlus (DE3)-RIL by two different steps of anion exchange chromatography, dialysis, hydroxyapatite chromatography, another step of anion exchange chromatography, and gel filtration, to homogeneity
recombinant His-tagged DHDPS 9.7fold from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged DHDPS from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant His-tagged enzyme 8fold from Escherichia coli strain BL21 (DE3) by immobilized metal affinity chromatography and gel filtration
recombinant His-tagged enzyme from Escherichia coli strain BL21 (DE3) Star by nickel affinity chromatography, cleavage of the His-tag by TEV protease
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by metal affinity chromatography
recombinant His-tagged enzyme from Escherichia coli strain XL1-Blue by nickel affinity chromatography
-
recombinant His-tagged isozyme from Escherichia coli strain BL21(DE3) by metal affinity chromatography
recombinant His-tagged isozymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 Star (DE3) by nickel affinity chromatography and gel filtration
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, the proteolytic cleavage by TEV protease does not remove the N-terminal His6-tag efficiently
recombinant N-terminally His6-tagged enzyme from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography, tag cleavage by thrombin, and gel filtration
-
recombinant wild-type 5.8fold, recombinant mutant Y107F 17.6fold, recombinant mutant T44V 15.8fold, and recombinant mutant Y133F 18fold
wild-type DHDPS, and the coupling enzyme, DHDPR, by ammonium sulphate fractionation
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
amplified product cloned into a pCR-Blunt IITOP vector, producing the construct pNS01. DHDPS gene then subcloned into the Escherichia coli expression vector Champion pET101/D-TOPO to produce pNS02. Native recombinant protein overexpressed in Escherichia coli BL21 (DE3)
-
dapA gene (Rv2753c) is cloned and expressed in Escherichia coli
dapA gene encoding DHDPS amplified and cloned into the pET11a expression vector, expressed in Escherichia coli BL21-DE3
Q81WN7
DHDPS overexpressed in Escherichia coli AT997recA-, transformed with site-directed mutants based on the pBluescript plasmid pJG001
DNA and amino acid sequence determination and analysis, recombinant expression in Escherichia coli strain BL21(DE3)
-
expressed in Escherichia coli BL21 (DE3), pET11a expression vector
expressed in Escherichia coli BL21(DE3), full length dapA gene (DHDPS-FL) and C-terminal variant (DHDPS D228-295) lacking the three helical domains, pET22b vector
expressed in Escherichia coli BL21(DE3), pET24d vector
expressed in Escherichia coli XL-1 Blue harbouring the plasmid pJG001
expressed in Escherichia coli XL1-blue, pBluescript vector, recombinant protein
expressed in Escherichia coli, BL21 (DE3) strain carrying the Cbot-DHDPS gene (DapA)
-
expressed in Escherichia coli, pJG001 plasmid for site-directed mutagenesis, mutant Y107W expressed in dapA-negative strain AT997r-
expression in Escherichia coli
expression of N-terminally His6-tagged enzyme with a thrombin cleavage site in Escherichia coli strain BL21 (DE3)
-
gene dapA or Aq_1143, sequence comparisons, recombinant enzyme expression in Escherichia coli strain BL21-CodonPlus (DE3)-RIL
gene dapA, DNA and amino acid sequence determination and analysis, expression of His-tagged DHDPS in Escherichia coli strain BL21(DE3)
gene dapA, expression of His-tagged DHDPS in Escherichia coli strain BL21(DE3)
-
gene dapA, expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene dapA, expression of His-tagged enzyme in Escherichia coli strain XL1-Blue
-
gene dapA, expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)
gene dapA, expression of wild-type and mutant enzymes in Escherichia coli strain BL21 (DE3)
-
gene dapA, overexpression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 Star (DE3)
-
gene dapA, recombinant expression of lysine-insensitive mutants in Escherichia coli strain MG1655 with a yield improved by 46% compared to the wild-type enzyme
-
gene dapA, sequence comparison with Escherichia coli enzyme, expression of His-tagged enzyme in Escherichia coli strain BL21 (DE3)
gene dapA1, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
gene dapA10, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
gene dapA2, sequence comparisons, expression of the His-tagged isozyme in Escherichia coli strain BL21(DE3)
gene dapA3, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
gene dapA4, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
gene dapA5, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
gene dapA6, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
gene dapA7, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
gene dapA8, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
gene dapA9, sequence comparisons, expression of the His-tagged enzyme isozyme in Escherichia coli strain BL21(DE3)
inserted into the vector pET11a and transformed into Escherichia coli strain CodonPlus BL21 (DE3)
-
into pBI121 vector in order to obtain fusion construct of the DHDPS sequence with the reporter gene GUS transiently expressed in the onion epidermal cells by particle gun-mediated bombardment. DHDPS cDNA coding sequence subcloned into the pUC18 plasmid and expressed in Escherichia coli strain AT997, an auxotroph lacking DHDPS activity
into the expression vector pET151-D to give the plasmid pFH02, to transform chemically super-competent Escherichia coli Top10 cells
into the pET-21a expression vector and introduced into Escherichia coli Rosetta (DE3) strain
isozymes MtDHDPS, MtDHDPS2, MtDHDPS3, and MtDHDPS4, phylogenetic analysis, quantitative RT-PCR expression analysis, the different isogenes are transcriptionally regulated in an organ-specific manner, subcloning in Escherichia coli strain DH5alpha, expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3), coexpresion of His-tagged isozyme MtDHDPS3 with N-terminally FLAG-tagged enzyme AtDHDPS2 from Arabidopsis thliana in Escherichia coli strain BL21(DE3), expression of isozyme MtDHDPS3 in transgenic Arabidopsis thaliana plants under the control of a constitutive 35S promoter via Agrobacterium tumefaciens transfection resulting in an inhibition of enzyme activity
-
ligated into the expression vector pET30a and transformed into the Escherichia coli strain B834 for overexpression
orf AT2G45440, recombinant His-tagged enzyme expression in Escherichia coli strain BL21 (DE3) Star
PCR product ligated into pCRBluntII-TOPO and transformed into Escherichia coli One Shot TOP10. The dapA insert then amplified, the product, which now contains NdeI and BamHI restriction-endonuclease sites, ligated into pCR-BluntII-TOPO and transformed into Escherichia coli One Shot TOP10, which enables efficient ligation into an expression vector. DapA and linearized pET-11a ligated with T4 DNA ligase and transformed into Escherichia coli BL21(DE3)
Q81WN7
plasmid pB3935 containing a His-tagged copy of the dapA2 gene and a gene conferring kanamycin resistance, transformed into Escherichia coli BL21(DE3) for protein overexpression
Q81WN7
recombinant enzyme expression in Escherichia coli strain XL-1 Blue using plasmid pJG001
recombinant His-tagged protein is expressed in Escherichia coli BL-21(DE3)
-
the dapA and dapA-H225* genes introduced into the vector pUCX, to transform the auxotrophic Escherichia coli XL1-Blue KanRDELTAdapA cells, under the control of a lac promoter/repressor system. Mutations in dapA introduced into the pET-151/D-TOPO plasmid. C-terminal truncated DHDPS (H225*) expressed in Escherichia coli BL21 Star (DE3)
the dapA open reading frame is cloned in the expression vector pET28a for expression as N-terminal 6 x His-tagged protein
wild-type and mutant cloned into plasmid pET-151/D-TOPO and expressed in Escherichia coli BL21 Star (DE3) competent cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
high level expression is present in fast-growing tissue and reproductive tissue. The 5'-regulatory sequence of DHDPS contains a GT-1 box and a (CA)n element, which may play a role in regulating the expression of DHDPS
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
-
expression of dapA gene of E coli, insensitive to feedback-inhibition by L-lysine
biotechnology
drug development
food industry
industry
considering the industrial application of this protein, such as its use for lysine biosynthesis, stable conformation via tight tetramerization interfaces may make this valuable protein to be more useful
medicine
pharmacology
synthesis
the enzyme can be commercially exploited for high-yield production of (S)-lysine
additional information
biotechnology
-
enzyme is a target for herbicide and anti-microbial action
-
drug development
the allosteric binding site of DHDPS may be a good starting point for development of an inhibitor specific to Neisseria meningitidis
drug development
the intracellular enzyme dihydrodipicolinate synthase a potential drug target because it is essential for the growth of bacteria while it is absent in humans
drug development
the enzyme is a bona fide drug target for treatment of the Crown Gall disease on crops caused by Agrobacterium tumefaciens, rational design of pesticide agents
drug development
the enzyme is an attractive target for rational antibiotic and herbicide design
drug development
the enzyme is an attractive target for the design and synthesis of herbicides and antibiotics
drug development
Agrobacterium tumefaciens C58 / ATCC 33970
-
the enzyme is a bona fide drug target for treatment of the Crown Gall disease on crops caused by Agrobacterium tumefaciens, rational design of pesticide agents
-
drug development
-
the allosteric binding site of DHDPS may be a good starting point for development of an inhibitor specific to Neisseria meningitidis
-
food industry
L-lysine, one of the essential amino acids required for nutrition in animals and humans, is widely used in the food industry, medical industry, etc. L-lysine has been mainly produced by microbial fermentation employing mutant strains of bacteria. An L-lysine high-yielding strain is developed by modification of aspartokinase III and dihydrodipicolinate synthetase
food industry
Escherichia coli LATR11
-
L-lysine, one of the essential amino acids required for nutrition in animals and humans, is widely used in the food industry, medical industry, etc. L-lysine has been mainly produced by microbial fermentation employing mutant strains of bacteria. An L-lysine high-yielding strain is developed by modification of aspartokinase III and dihydrodipicolinate synthetase
-
medicine
-
development of species-specific inhibitors of DHDPS as potential antibacterials
medicine
-
development of species-specific inhibitors of DHDPS as potential antibacterials
medicine
-
development of species-specific inhibitors of DHDPS as potential antibacterials
medicine
L-lysine, one of the essential amino acids required for nutritionin animals and humans, is widely used in the food industry, medical industry, etc. L-lysine has been mainly produced by microbial fermentation employing mutant strains of bacteria. An L-lysine high-yielding strain is developed by modification of aspartokinase III and dihydrodipicolinate synthetase
medicine
Escherichia coli LATR11
-
L-lysine, one of the essential amino acids required for nutritionin animals and humans, is widely used in the food industry, medical industry, etc. L-lysine has been mainly produced by microbial fermentation employing mutant strains of bacteria. An L-lysine high-yielding strain is developed by modification of aspartokinase III and dihydrodipicolinate synthetase
-
pharmacology
enzyme structure analysis for design of novel therapeutics against bacterial pathogen
pharmacology
structure of the enzyme guides the design of novel therapeutics against the methicillin-resistant pathogen
pharmacology
-
structure of the enzyme guides the design of novel therapeutics against the methicillin-resistant pathogen
-
pharmacology
-
enzyme structure analysis for design of novel therapeutics against bacterial pathogen
-
additional information
the enzyme is not an optimal target for drug development against Pseudomonas aeruginosa
additional information
-
the enzyme is not an optimal target for drug development against Pseudomonas aeruginosa
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bakhiet, N.; Forney, F.W.; Stahly, D.P.; Daniels, L.
Lysine biosynthesis in Methanobacterium thermoautotrophicum is by the diaminopimelic acid pathway
Curr. Microbiol.
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195-198
1984
Methanothermobacter thermautotrophicus
-
brenda
Kumpaisal, R.; Hashimoto, T.; Yamada, Y.
Purification and characterization of dihydrodipicolinate synthase from wheat suspension cultures
Plant Physiol.
85
145-151
1987
Triticum aestivum
brenda
Wallsgrove, R.M.; Mazelis, M.
Spinach leaf dihydrodipicolinate synthase: partial purification and characterization
Phytochemistry
20
2651-2655
1981
Pisum sativum, Spinacia oleracea
-
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Mazelis, M.; Watley, F.R.; Whatley, J.
The enzymology of lysine biosynthesis in higher plants. The occurrence, characterization and some regulatory properties of dihydrodipicolinate synthase
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84
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Brassica sp., Cucurbita sp., Phaseolus sp., Solanum tuberosum, Spinacia oleracea, Triticum aestivum, Zea mays
brenda
Halling, S.M.; Stahly, D.P.
Dihydrodipicolinic acid synthase of Bacillus licheniformis. Quaternary structure, kinetics, and stability in the presence of sodium chloride and substrates
Biochim. Biophys. Acta
452
580-596
1976
Bacillus licheniformis
brenda
Yamakura, F.; Ikeda, Y.; Kimura, K.; Sasakawa, T.
Partial purification and some properties of pyruvate-aspartic semialdehyde condensing enzyme from sporulating Bacillus subtilis
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611-621
1974
Bacillus subtilis
brenda
Shedlarski, J.G.
Pyruvate-aspartic semialdehyde condensing enzyme (Escherichia coli)
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17B
129-134
1971
Escherichia coli
-
brenda
Webster, F.H.; Lechowich, R.V.
Partial purification and characterization of dihydrodipicolinic acid synthetase from sporulating Bacillus megaterium
J. Bacteriol.
101
118-126
1970
Priestia megaterium
brenda
Shedlarski, J.G.; Gilvarg, C.
The pyruvate-aspartic semialdehyde condensing enzyme of Escherichia coli
J. Biol. Chem.
245
1362-1373
1970
Escherichia coli
brenda
Stahly, D.P.
Dihydrodipicolinic acid synthase of Bacillus licheniformis
Biochim. Biophys. Acta
191
439-451
1969
Bacillus licheniformis
brenda
Frisch, D.A.; Gengenbach, B.G.; Tommy, A.M.; Sellner, J.M.; Somers, D.A.; Myers, D.E.
Isolation and characterization of dihydrodipicolinate synthase from maize
Plant Physiol.
96
444-452
1991
Zea mays
brenda
Laber, B.; Gomis-Rueth, F.X.; Romao, M.J.; Huber, R.
Escherichia coli dihydrodipicolinate synthase. Identification of the active site and crystallization
Biochem. J.
268
691-695
1992
Escherichia coli
-
brenda
Mirwaldt, C.; Korndoerfer, I.; Huber, R.
The crystal structure of dihydrodipicolinate synthase from Escherichia coli at 2.5 A resolution
J. Mol. Biol.
246
227-239
1995
Escherichia coli
brenda
Selli, A.; Crociani, F.; DiGioia, D.; Fava, F.; Crisetig, G.; Matteuzzi, D.
Regulation of dihydrodipicolinate synthase and diaminopimelate decarboxylase activity in Bacillus stearothermophilus
Ital. J. Biochem.
43
29-35
1994
Geobacillus stearothermophilus
brenda
Dereppe, C.; Bold, G.; Ghisalba, O.; Ebert, E.; Schaer, H.P.
Purification and characterization of dihydrodipicolinate synthase from pea
Plant Physiol.
98
813-821
1991
Pisum sativum
brenda
Perl, A.; Shaul, O.; Galili, G.
Regulation of lysine synthesis in transgenic potato plants expressing a bacterial dihydrodipicolinate synthase in their chloroplasts
Plant Mol. Biol.
19
815-823
1992
Escherichia coli, Solanum tuberosum
brenda
Shaul, O.; Galili, G.
Concerted regulation of lysine and threonine synthesis in tobacco plants expressing bacterial feedback-insensitive aspartate kinase and dihydrodipicolinate synthase
Plant Mol. Biol.
23
759-768
1993
Escherichia coli, Nicotiana tabacum
brenda
Couper, L.; McKendrick, J.E.; Robins, D.J.
Pyridine and piperidine derivatives as inhibitors of dihydrdipicolinic acid synthase, a key enzyme in the diaminopimelate pathway to L-lysine
Bioorg. Med. Chem. Lett.
4
2267-2272
1994
Escherichia coli
-
brenda
Brinch-Pedersen, H.; Galili, G.; Knudsen, S.; Holm, P.B.
Engineering of the aspartate family biosynthetic pathway in barley (Hordeum vulgare L.) by transformation with heterologous genes encoding feed-back-insensitive aspartate kinase and dihydrodipicolinate synthase
Plant Mol. Biol.
32
611-620
1996
Hordeum vulgare
brenda
Karsten, W.E.
Dihydrodipicolinate synthase from Escherichia coli: pH dependent changes in the kinetic mechanism and kinetic mechanism of allosteric inhibition by L-lysine
Biochemistry
36
1730-1739
1997
Escherichia coli
brenda
Blickling, S.; Beisel, H.G.; Bozic, D.; Knaeblein, J.; Laber, B.; Huber, R.
Structure of dihydrodipicolinate synthase of Nicotiana sylvestris reveals novel quaternary structure
J. Mol. Biol.
274
608-621
1997
Nicotiana sylvestris
brenda
Blickling, S.; Knaeblein, J.
Feedback inhibition of dihydrodipicolinate synthase enzymes by L-lysine
Biol. Chem.
378
207-210
1997
Escherichia coli
brenda
Vauterin, M.; Frankhard, V.; Jacobs, M.
The Arabidopsis thaliana dhdps gene encoding dihydrodipicolinate synthase, key enzyme of lysine biosynthesis, is expressed in a cell-specific manner
Plant Mol. Biol.
39
695-708
1990
Arabidopsis thaliana
brenda
Bonnassie, S.; Oreglia, J.; Sicard, A.M.
Nucleotide sequence of the dapA gene from Corynebacterium glutamicum
Nucleic Acids Res.
18
6421
1990
Corynebacterium glutamicum
brenda
Dobson, R.C.; Gerrard, J.A.; Pearce, F.G.
Dihydrodipicolinate synthase is not inhibited by its substrate, (S)-aspartate beta-semialdehyde
Biochem. J.
377
757-762
2004
Escherichia coli, Escherichia coli XL1-Blue
brenda
Dobson, R.C.; Valegard, K.; Gerrard, J.A.
The crystal structure of three site-directed mutants of Escherichia coli dihydrodipicolinate synthase: further evidence for a catalytic triad
J. Mol. Biol.
338
329-339
2004
Escherichia coli (P0A6L2), Escherichia coli
brenda
Dobson, R.C.; Griffin, M.D.; Jameson, G.B.; Gerrard, J.A.
The crystal structures of native and (S)-lysine-bound dihydrodipicolinate synthase from Escherichia coli with improved resolution show new features of biological significance
Acta Crystallogr. Sect. D
61
1116-1124
2005
Escherichia coli (P0A6L2), Escherichia coli
brenda
Dobson, R.C.; Devenish, S.R.; Turner, L.A.; Clifford, V.R.; Pearce, F.G.; Jameson, G.B.; Gerrard, J.A.
Role of arginine 138 in the catalysis and regulation of Escherichia coli dihydrodipicolinate synthase
Biochemistry
44
13007-13013
2005
Escherichia coli (P0A6L2), Escherichia coli
brenda
Dobson, R.C.; Griffin, M.D.; Roberts, S.J.; Gerrard, J.A.
Dihydrodipicolinate synthase (DHDPS) from Escherichia coli displays partial mixed inhibition with respect to its first substrate, pyruvate
Biochimie
86
311-315
2004
Escherichia coli
brenda
Turner, J.J.; Gerrard, J.A.; Hutton, C.A.
Heterocyclic inhibitors of dihydrodipicolinate synthase are not competitive
Bioorg. Med. Chem.
13
2133-2140
2005
Escherichia coli
brenda
Blagova, E.; Levdikov, V.; Milioti, N.; Fogg, M.J.; Kalliomaa, A.K.; Brannigan, J.A.; Wilson, K.S.; Wilkinson, A.J.
Crystal structure of dihydrodipicolinate synthase (BA3935) from Bacillus anthracis at 1.94 A resolution
Proteins
62
297-301
2005
Bacillus anthracis (Q81WN7), Bacillus anthracis
brenda
Kefala, G.; Weiss, M.S.
Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DapA (Rv2753c) from Mycobacterium tuberculosis
Acta Crystallogr. Sect. F
62
1116-1119
2006
Mycobacterium tuberculosis
brenda
Leduc, Y.A.; Phenix, C.P.; Puttick, J.; Nienaber, K.; Palmer, D.R.; Delbaere, L.T.
Crystallization, preliminary X-ray diffraction and structure solution of MosA, a dihydrodipicolinate synthase from Sinorhizobium meliloti L5-30
Acta Crystallogr. Sect. F
62
49-51
2006
Sinorhizobium meliloti, Sinorhizobium meliloti L5-30
brenda
Pearce, F.G.; Perugini, M.A.; McKerchar, H.J.; Gerrard, J.A.
Dihydrodipicolinate synthase from Thermotoga maritima
Biochem. J.
400
359-366
2006
Thermotoga maritima (Q9X1K9), Thermotoga maritima
brenda
Kefala, G.; Evans, G.; Griffin, M.D.; Devenish, S.R.; Perugini, M.A.; Gerrard, J.A.; Weiss, M.S.; Dobson, R.C.
Crystal structure and kinetic study of dihydrodipicolinate synthase from Mycobacterium tuberculosis
Biochem. J.
411
351-360
2008
Mycobacterium tuberculosis (P9WP25), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WP25)
brenda
Mitsakos, V.; Dobson, R.C.; Pearce, F.G.; Devenish, S.R.; Evans, G.L.; Burgess, B.R.; Perugini, M.A.; Gerrard, J.A.; Hutton, C.A.
Inhibiting dihydrodipicolinate synthase across species: Towards specificity for pathogens?
Bioorg. Med. Chem. Lett.
18
842-844
2007
Escherichia coli, Staphylococcus aureus, Mycobacterium tuberculosis
brenda
Varisi, V.A.; Medici, L.O.; van der Meer, I.; Lea, P.J.; Azevedo, R.A.
Dihydrodipicolinate synthase in opaque and floury maize mutants
Plant Sci.
173
458-467
2007
Zea mays
brenda
Devenish, S.R.; Gerrard, J.A.; Jameson, G.B.; Dobson, R.C.
The high-resolution structure of dihydrodipicolinate synthase from Escherichia coli bound to its first substrate, pyruvate
Acta Crystallogr. Sect. F
64
1092-1095
2008
Escherichia coli (P0A6L2), Escherichia coli
brenda
Dobson, R.C.; Atkinson, S.C.; Gorman, M.A.; Newman, J.M.; Parker, M.W.; Perugini, M.A.
The purification, crystallization and preliminary X-ray diffraction analysis of dihydrodipicolinate synthase from Clostridium botulinum
Acta Crystallogr. Sect. F
64
206-208
2008
Clostridium botulinum
brenda
Burgess, B.R.; Dobson, R.C.; Dogovski, C.; Jameson, G.B.; Parker, M.W.; Perugini, M.A.
Purification, crystallization and preliminary X-ray diffraction studies to near-atomic resolution of dihydrodipicolinate synthase from methicillin-resistant Staphylococcus aureus
Acta Crystallogr. Sect. F
64
659-661
2008
Staphylococcus aureus (Q6GH13), Staphylococcus aureus, Staphylococcus aureus MRSA252 (Q6GH13)
brenda
Rice, E.A.; Bannon, G.A.; Glenn, K.C.; Jeong, S.S.; Sturman, E.J.; Rydel, T.J.
Characterization and crystal structure of lysine insensitive Corynebacterium glutamicum dihydrodipicolinate synthase (cDHDPS) protein
Arch. Biochem. Biophys.
480
111-121
2008
Corynebacterium glutamicum (P19808), Corynebacterium glutamicum
brenda
Pearce, F.G.; Dobson, R.C.; Weber, A.; Lane, L.A.; McCammon, M.G.; Squire, M.A.; Perugini, M.A.; Jameson, G.B.; Robinson, C.V.; Gerrard, J.A.
Mutating the tight-dimer interface of dihydrodipicolinate synthase disrupts the enzyme quaternary structure: toward a monomeric enzyme
Biochemistry
47
12108-12117
2008
Escherichia coli (P0A6L2)
brenda
Phenix, C.P.; Palmer, D.R.
Isothermal titration microcalorimetry reveals the cooperative and noncompetitive nature of inhibition of Sinorhizobium meliloti L5-30 dihydrodipicolinate synthase by (S)-lysine
Biochemistry
47
7779-7781
2008
Sinorhizobium meliloti (Q07607), Sinorhizobium meliloti L5-30 (Q07607), Sinorhizobium meliloti L5-30
brenda
Boughton, B.A.; Griffin, M.D.; ODonnell, P.A.; Dobson, R.C.; Perugini, M.A.; Gerrard, J.A.; Hutton, C.A.
Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues
Bioorg. Med. Chem.
16
9975-9983
2008
Escherichia coli (P0A6L2)
brenda
Boughton, B.A.; Dobson, R.C.; Gerrard, J.A.; Hutton, C.A.
Conformationally constrained diketopimelic acid analogues as inhibitors of dihydrodipicolinate synthase
Bioorg. Med. Chem. Lett.
18
460-463
2008
Escherichia coli (P0A6L2)
brenda
Phenix, C.P.; Nienaber, K.; Tam, P.H.; Delbaere, L.T.; Palmer, D.R.
Structural, functional and calorimetric investigation of MosA, a dihydrodipicolinate synthase from Sinorhizobium meliloti l5-30, does not support involvement in rhizopine biosynthesis
ChemBioChem
9
1591-1602
2008
Sinorhizobium meliloti (Q07607), Sinorhizobium meliloti L5-30 (Q07607), Sinorhizobium meliloti L5-30
brenda
Wolterink-van Loo, S.; Levisson, M.; Cabrieres, M.C.; Franssen, M.C.; van der Oost, J.
Characterization of a thermostable dihydrodipicolinate synthase from Thermoanaerobacter tengcongensis
Extremophiles
12
461-469
2008
Caldanaerobacter subterraneus subsp. tengcongensis (Q8RBI5), Caldanaerobacter subterraneus subsp. tengcongensis
brenda
Girish, T.S.; Sharma, E.; Gopal, B.
Structural and functional characterization of Staphylococcus aureus dihydrodipicolinate synthase
FEBS Lett.
582
2923-2930
2008
Staphylococcus aureus (Q5HG25), Staphylococcus aureus, Staphylococcus aureus COL (Q5HG25)
brenda
Burgess, B.R.; Dobson, R.C.; Bailey, M.F.; Atkinson, S.C.; Griffin, M.D.; Jameson, G.B.; Parker, M.W.; Gerrard, J.A.; Perugini, M.A.
Structure and evolution of a novel dimeric enzyme from a clinically important bacterial pathogen
J. Biol. Chem.
283
27598-27603
2008
Staphylococcus aureus (Q6GH13), Staphylococcus aureus, Staphylococcus aureus MRSA252 (Q6GH13)
brenda
Dobson, R.C.; Griffin, M.D.; Devenish, S.R.; Pearce, F.G.; Hutton, C.A.; Gerrard, J.A.; Jameson, G.B.; Perugini, M.A.
Conserved main-chain peptide distortions: a proposed role for Ile203 in catalysis by dihydrodipicolinate synthase
Protein Sci.
17
2080-2090
2008
Escherichia coli (P0A6L2), Escherichia coli
brenda
Padmanabhan, B.; Strange, R.W.; Antonyuk, S.V.; Ellis, M.J.; Hasnain, S.S.; Iino, H.; Agari, Y.; Bessho, Y.; Yokoyama, S.
Structure of dihydrodipicolinate synthase from Methanocaldococcus jannaschii
Acta Crystallogr. Sect. F
65
1222-1226
2009
Methanocaldococcus jannaschii (Q57695), Methanocaldococcus jannaschii
brenda
Voss, J.E.; Scally, S.W.; Taylor, N.L.; Dogovski, C.; Alderton, M.R.; Hutton, C.A.; Gerrard, J.A.; Parker, M.W.; Dobson, R.C.; Perugini, M.A.
Expression, purification, crystallization and preliminary X-ray diffraction analysis of dihydrodipicolinate synthase from Bacillus anthracis in the presence of pyruvate
Acta Crystallogr. Sect. F
65
188-191
2009
Bacillus anthracis (Q81WN7), Bacillus anthracis, Bacillus anthracis Sterne (Q81WN7)
brenda
Atkinson, S.C.; Dobson, R.C.; Newman, J.M.; Gorman, M.A.; Dogovski, C.; Parker, M.W.; Perugini, M.A.
Crystallization and preliminary X-ray analysis of dihydrodipicolinate synthase from Clostridium botulinum in the presence of its substrate pyruvate
Acta Crystallogr. Sect. F
65
253-255
2009
Clostridium botulinum
brenda
Sibarani, N.E.; Gorman, M.A.; Dogovski, C.; Parker, M.W.; Perugini, M.A.
Crystallization of dihydrodipicolinate synthase from a clinical isolate of Streptococcus pneumoniae
Acta Crystallogr. Sect. F
66
32-36
2010
Streptococcus pneumoniae, Streptococcus pneumoniae OXC141
brenda
Griffin, M.D.; Dobson, R.C.; Gerrard, J.A.; Perugini, M.A.
Exploring the dihydrodipicolinate synthase tetramer: how resilient is the dimer-dimer interface?
Arch. Biochem. Biophys.
494
58-63
2010
Escherichia coli (P0A6L2)
brenda
Guo, B.B.; Devenish, S.R.; Dobson, R.C.; Muscroft-Taylor, A.C.; Gerrard, J.A.
The C-terminal domain of Escherichia coli dihydrodipicolinate synthase (DHDPS) is essential for maintenance of quaternary structure and efficient catalysis
Biochem. Biophys. Res. Commun.
380
802-806
2009
Escherichia coli (P0A6L2), Escherichia coli
brenda
Devenish, S.R.; Huisman, F.H.; Parker, E.J.; Hadfield, A.T.; Gerrard, J.A.
Cloning and characterisation of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis
Biochim. Biophys. Acta
1794
1168-1174
2009
Escherichia coli, Neisseria meningitidis (Q9JZR4), Neisseria meningitidis, Neisseria meningitidis MC58 (Q9JZR4)
brenda
Domigan, L.J.; Scally, S.W.; Fogg, M.J.; Hutton, C.A.; Perugini, M.A.; Dobson, R.C.; Muscroft-Taylor, A.C.; Gerrard, J.A.; Devenish, S.R.
Characterisation of dihydrodipicolinate synthase (DHDPS) from Bacillus anthracis
Biochim. Biophys. Acta
1794
1510-1516
2009
Escherichia coli, Bacillus anthracis (Q81WN7), Bacillus anthracis
brenda
Dobson, R.C.; Perugini, M.A.; Jameson, G.B.; Gerrard, J.A.
Specificity versus catalytic potency: The role of threonine 44 in Escherichia coli dihydrodipicolinate synthase mediated catalysis
Biochimie
91
1036-1044
2009
Escherichia coli (P0A6L2), Escherichia coli
brenda
Muscroft-Taylor, A.C.; Soares da Costa, T.P.; Gerrard, J.A.
New insights into the mechanism of dihydrodipicolinate synthase using isothermal titration calorimetry
Biochimie
92
254-262
2010
Thermotoga maritima, Escherichia coli (P0A6L2), Escherichia coli
brenda
Soares da Costa, T.P.; Muscroft-Taylor, A.C.; Dobson, R.C.; Devenish, S.R.; Jameson, G.B.; Gerrard, J.A.
How essential is the essential active-site lysine in dihydrodipicolinate synthase?
Biochimie
92
837-845
2010
Escherichia coli (P0A6L2), Escherichia coli
brenda
Kang, B.S.; Kim, Y.G.; Ahn, J.W.; Kim, K.J.
Crystal structure of dihydrodipicolinate synthase from Hahella chejuensis at 1.5 A resolution
Int. J. Biol. Macromol.
46
512-516
2010
Hahella chejuensis (Q2S9K4), Hahella chejuensis
brenda
Voss, J.E.; Scally, S.W.; Taylor, N.L.; Atkinson, S.C.; Griffin, M.D.; Hutton, C.A.; Parker, M.W.; Alderton, M.R.; Gerrard, J.A.; Dobson, R.C.; Dogovski, C.; Perugini, M.A.
Substrate-mediated stabilization of a tetrameric drug target reveals Achilles heel in anthrax
J. Biol. Chem.
285
5188-5195
2010
Bacillus anthracis (Q81WN7), Bacillus anthracis, Bacillus anthracis Sterne (Q81WN7)
brenda
Orsburn, B.C.; Melville, S.B.; Popham, D.L.
EtfA catalyses the formation of dipicolinic acid in Clostridium perfringens
Mol. Microbiol.
75
178-186
2010
Clostridium botulinum
brenda
Kong, F.; Jiang, S.; Meng, X.; Song, C.; Shi, J.; Jin, D.; Jiang, S.; Wang, B.
Cloning and characterization of the DHDPS gene encoding the lysine biosynthetic enzyme dihydrodipocolinate synthase from Zizania latifolia (Griseb)
Plant Mol. Biol. Rep.
27
199-208
2009
Zizania latifolia (Q1PDD5)
-
brenda
Devenish, S.R.; Blunt, J.W.; Gerrard, J.A.
NMR studies uncover alternate substrates for dihydrodipicolinate synthase and suggest that dihydrodipicolinate reductase is also a dehydratase
J. Med. Chem.
53
4808-4812
2010
Escherichia coli
brenda
Wubben, J.M.; Dogovski, C.; Dobson, R.C.; Codd, R.; Gerrard, J.A.; Parker, M.W.; Perugini, M.A.
Cloning, expression, purification and crystallization of dihydrodipicolinate synthase from the psychrophile Shewanella benthica
Acta Crystallogr. Sect. F
66
1511-1516
2010
Shewanella benthica, Shewanella benthica ATCC 3392
brenda
Muscroft-Taylor, A.C.; Catchpole, R.J.; Dobson, R.C.; Pearce, F.G.; Perugini, M.A.; Gerrard, J.A.
Disruption of quaternary structure in Escherichia coli dihydrodipicolinate synthase (DHDPS) generates a functional monomer that is no longer inhibited by lysine
Arch. Biochem. Biophys.
503
202-206
2010
Escherichia coli
brenda
Evans, G.; Schuldt, L.; Griffin, M.D.; Devenish, S.R.; Grant Pearce, F.; Perugini, M.A.; Dobson, R.C.; Jameson, G.B.; Weiss, M.S.; Gerrard, J.A.
A tetrameric structure is not essential for activity in dihydrodipicolinate synthase (DHDPS) from Mycobacterium tuberculosis
Arch. Biochem. Biophys.
512
154-159
2011
Mycobacterium tuberculosis
brenda
Pearce, F.G.; Dobson, R.C.; Jameson, G.B.; Perugini, M.A.; Gerrard, J.A.
Characterization of monomeric dihydrodipicolinate synthase variant reveals the importance of substrate binding in optimizing oligomerization
Biochim. Biophys. Acta
1814
1900-1909
2011
Thermotoga maritima
brenda
Kaur, N.; Gautam, A.; Kumar, S.; Singh, A.; Singh, N.; Sharma, S.; Sharma, R.; Tewari, R.; Singh, T.P.
Biochemical studies and crystal structure determination of dihydrodipicolinate synthase from Pseudomonas aeruginosa
Int. J. Biol. Macromol.
48
779-787
2011
no activity in Homo sapiens, Pseudomonas aeruginosa (Q9I4W3), Pseudomonas aeruginosa
brenda
Blickling, S.; Renner, C.; Laber, B.; Pohlenz, H.; Holak, T.; Huber, R.
Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated by X-ray crystallography and NMR spectroscopy
Biochemistry
36
24-33
1997
Escherichia coli (P0A6L2), Escherichia coli
brenda
Schnell, R.; Oehlmann, W.; Sandalova, T.; Braun, Y.; Huck, C.; Maringer, M.; Singh, M.; Schneider, G.
Tetrahydrodipicolinate N-succinyltransferase and dihydrodipicolinate synthase from Pseudomonas aeruginosa: structure analysis and gene deletion
PLoS ONE
7
e31133
2012
Pseudomonas aeruginosa (Q9I4W3), Pseudomonas aeruginosa
brenda
Griffin, M.D.; Billakanti, J.M.; Gerrard, J.A.; Dobson, R.C.; Pearce, F.G.
Crystallization and preliminary X-ray diffraction analysis of dihydrodipicolinate synthase 2 from Arabidopsis thaliana
Acta Crystallogr. Sect. F
67
1386-1390
2011
Arabidopsis thaliana (Q9FVC8), Arabidopsis thaliana
brenda
Atkinson, S.C.; Dogovski, C.; Newman, J.; Dobson, R.C.; Perugini, M.A.
Cloning, expression, purification and crystallization of dihydrodipicolinate synthase from the grapevine Vitis vinifera
Acta Crystallogr. Sect. F
67
1537-1541
2011
Vitis vinifera
brenda
Atkinson, S.C.; Dogovski, C.; Dobson, R.C.; Perugini, M.A.
Cloning, expression, purification and crystallization of dihydrodipicolinate synthase from Agrobacterium tumefaciens
Acta Crystallogr. Sect. F
68
1040-1047
2012
Agrobacterium tumefaciens (Q8UGL3), Agrobacterium tumefaciens, Agrobacterium tumefaciens C58 / ATCC 33970 (Q8UGL3)
brenda
Siddiqui, T.; Paxman, J.J.; Dogovski, C.; Panjikar, S.; Perugini, M.A.
Cloning to crystallization of dihydrodipicolinate synthase from the intracellular pathogen Legionella pneumophila
Acta Crystallogr. Sect. F
69
1177-1181
2013
Legionella pneumophila
brenda
Geng, F.; Chen, Z.; Zheng, P.; Sun, J.; Zeng, A.
Exploring the allosteric mechanism of dihydrodipicolinate synthase by reverse engineering of the allosteric inhibitor binding sites and its application for lysine production
Appl. Microbiol. Biotechnol.
97
1963-1971
2012
Corynebacterium glutamicum, Escherichia coli, Corynebacterium glutamicum ATCC 13032, Escherichia coli MG1655
brenda
Skovpen, Y.V.; Palmer, D.R.
Dihydrodipicolinate synthase from Campylobacter jejuni: kinetic mechanism of cooperative allosteric inhibition and inhibitor-induced substrate cooperativity
Biochemistry
52
5454-5462
2013
Campylobacter jejuni
brenda
Boughton, B.A.; Hor, L.; Gerrard, J.A.; Hutton, C.A.
1,3-Phenylene bis(ketoacid) derivatives as inhibitors of Escherichia coli dihydrodipicolinate synthase
Bioorg. Med. Chem.
20
2419-2426
2012
Escherichia coli
brenda
Sridharan, U.; Ebihara, A.; Kuramitsu, S.; Yokoyama, S.; Kumarevel, T.; Ponnuraj, K.
Crystal structure and in silico studies of dihydrodipicolinate synthase (DHDPS) from Aquifex aeolicus
Extremophiles
18
973-985
2014
Aquifex aeolicus (O67216), Aquifex aeolicus
brenda
Erzeel, E.; Van Bochaute, P.; Thu, T.T.; Angenon, G.
Medicago truncatula dihydrodipicolinate synthase (DHDPS) enzymes display novel regulatory properties
Plant Mol. Biol.
81
401-415
2013
Medicago truncatula, Medicago truncatula Jemalong 2HA
brenda
Atkinson, S.C.; Dogovski, C.; Downton, M.T.; Czabotar, P.E.; Dobson, R.C.; Gerrard, J.A.; Wagner, J.; Perugini, M.A.
Structural, kinetic and computational investigation of Vitis vinifera DHDPS reveals new insight into the mechanism of lysine-mediated allosteric inhibition
Plant Mol. Biol.
81
431-446
2013
Vitis vinifera (D7U7T8), Vitis vinifera
brenda
Reboul, C.F.; Porebski, B.T.; Griffin, M.D.; Dobson, R.C.; Perugini, M.A.; Gerrard, J.A.; Buckle, A.M.
Structural and dynamic requirements for optimal activity of the essential bacterial enzyme dihydrodipicolinate synthase
PLoS Comput. Biol.
8
e1002537
2012
Escherichia coli, Staphylococcus aureus
brenda
Boughton, B.; Dobson, R.; Hutton, C.
The crystal structure of dihydrodipicolinate synthase from Escherichia coli with bound pyruvate and succinic acid semialdehyde: unambiguous resolution of the stereochemistry of the condensation product
Proteins
80
2117-2122
2012
Escherichia coli (P0A6L2), Escherichia coli
brenda
Atkinson, S.; Hor, L.; Dogovski, C.; Dobson, R.; Perugini, M.
Identification of the bona fide DHDPS from a common plant pathogen
Proteins
82
1869-1883
2014
Agrobacterium tumefaciens (A9CFV4), Agrobacterium tumefaciens (A9CGZ4), Agrobacterium tumefaciens (A9CHR2), Agrobacterium tumefaciens (A9CL94), Agrobacterium tumefaciens (A9CL97), Agrobacterium tumefaciens (Q7CU96), Agrobacterium tumefaciens (Q7D0E8), Agrobacterium tumefaciens (Q7D313), Agrobacterium tumefaciens (Q7D3Z9), Agrobacterium tumefaciens (Q8UGL3), Agrobacterium tumefaciens, Agrobacterium tumefaciens C58 / ATCC 33970 (A9CFV4), Agrobacterium tumefaciens C58 / ATCC 33970 (A9CGZ4), Agrobacterium tumefaciens C58 / ATCC 33970 (A9CHR2), Agrobacterium tumefaciens C58 / ATCC 33970 (A9CL94), Agrobacterium tumefaciens C58 / ATCC 33970 (A9CL97), Agrobacterium tumefaciens C58 / ATCC 33970 (Q7CU96), Agrobacterium tumefaciens C58 / ATCC 33970 (Q7D0E8), Agrobacterium tumefaciens C58 / ATCC 33970 (Q7D313), Agrobacterium tumefaciens C58 / ATCC 33970 (Q7D3Z9), Agrobacterium tumefaciens C58 / ATCC 33970 (Q8UGL3)
brenda
Shrivastava, P.; Navratna, V.; Silla, Y.; Dewangan, R.P.; Pramanik, A.; Chaudhary, S.; Rayasam, G.; Kumar, A.; Gopal, B.; Ramachandran, S.
Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues
Sci. Rep.
6
30827
2016
Mycobacterium tuberculosis (P9WP25), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WP25)
brenda
Christensen, J.B.; Soares da Costa, T.P.; Faou, P.; Pearce, F.G.; Panjikar, S.; Perugini, M.A.
Structure and function of cyanobacterial DHDPS and DHDPR
Sci. Rep.
6
37111
2016
Trichormus variabilis (Q3MFY8), Trichormus variabilis
brenda
Mank, N.; Arnette, A.; Klapper, V.; Offermann, L.; Chruszcz, M.
Structure of dihydrodipicolinate synthase from the commensal bacterium Bacteroides thetaiotaomicron at 2.1 A resolution
Acta Crystallogr. Sect. F
71
449-454
2015
Bacteroides thetaiotaomicron (Q8A3Z0), Bacteroides thetaiotaomicron, Bacteroides thetaiotaomicron ATCC 29148 (Q8A3Z0)
brenda
Naqvi, K.F.; Staker, B.L.; Dobson, R.C.; Serbzhinskiy, D.; Sankaran, B.; Myler, P.J.; Hudson, A.O.
Cloning, expression, purification, crystallization and X-ray diffraction analysis of dihydrodipicolinate synthase from the human pathogenic bacterium Bartonella henselae strain Houston-1 at 2.1 A resolution
Acta Crystallogr. Sect. F
72
2-9
2016
Bartonella henselae (Q6G468), Bartonella henselae, Bartonella henselae ATCC 49882 (Q6G468), Bartonella henselae Houston 1 (Q6G468)
brenda
Karsten, W.E.; Nimmo, S.A.; Liu, J.; Chooback, L.
Identification of 2, 3-dihydrodipicolinate as the product of the dihydrodipicolinate synthase reaction from Escherichia coli
Arch. Biochem. Biophys.
653
50-62
2018
Escherichia coli, Escherichia coli JM109
brenda
Xu, J.; Han, M.; Ren, X.; Zhang, W.
Modification of aspartokinase III and dihydrodipicolinate synthetase increases the production of L-lysine in Escherichia coli
Biochem. Eng. J.
114
79-86
2016
Escherichia coli (P0A6L2), Escherichia coli LATR11 (P0A6L2)
-
brenda
Sowole, M.A.; Simpson, S.; Skovpen, Y.V.; Palmer, D.R.; Konermann, L.
Evidence of allosteric enzyme regulation via changes in conformational dynamics A hydrogen/deuterium exchange investigation of dihydrodipicolinate synthase
Biochemistry
55
5413-5422
2016
Campylobacter jejuni
brenda
Ren, W.; Tao, J.; Shi, D.; Chen, W.; Chen, C.
Involvement of a dihydrodipicolinate synthase gene (FaDHDPS1) in fungal development, pathogenesis and stress responses in Fusarium asiaticum
BMC Microbiol.
18
128
2018
Fusarium asiaticum
brenda
Skovpen, Y.V.; Conly, C.J.; Sanders, D.A.; Palmer, D.R.
Biomimetic design results in a potent allosteric inhibitor of dihydrodipicolinate synthase from Campylobacter jejuni
J. Am. Chem. Soc.
138
2014-2020
2016
Campylobacter jejuni
brenda
Gupta, R.; Hogan, C.J.; Perugini, M.A.; Soares da Costa, T.P.
Characterization of recombinant dihydrodipicolinate synthase from the bread wheat Triticum aestivum
Planta
248
381-391
2018
Triticum aestivum (P24846), Triticum aestivum
brenda
Gupta, R.; Soares da Costa, T.P.; Faou, P.; Dogovski, C.; Perugini, M.A.
Comparison of untagged and his-tagged dihydrodipicolinate synthase from the enteric pathogen Vibrio cholerae
Protein Expr. Purif.
145
85-93
2018
Vibrio cholerae (A5F699), Vibrio cholerae, Vibrio cholerae O395 (A5F699)
brenda
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