BRENDA - Enzyme Database show

Structural and functional characterization of Staphylococcus aureus dihydrodipicolinate synthase

Girish, T.S.; Sharma, E.; Gopal, B.; FEBS Lett. 582, 2923-2930 (2008)

Data extracted from this reference:

Application
EC Number
Application
Commentary
Organism
4.3.3.7
pharmacology
enzyme structure analysis for design of novel therapeutics against bacterial pathogen
Staphylococcus aureus
Cloned(Commentary)
EC Number
Commentary
Organism
4.3.3.7
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
Staphylococcus aureus
Crystallization (Commentary)
EC Number
Crystallization
Organism
4.3.3.7
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
Staphylococcus aureus
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
L-lysine
poor feedback inhibition by
Staphylococcus aureus
KM Value [mM]
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
4.3.3.7
0.12
-
pyruvate
-
Staphylococcus aureus
4.3.3.7
0.33
-
(S)-aspartate 4-semialdehyde
-
Staphylococcus aureus
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
Staphylococcus aureus
-
dihydrodipicolinate + H2O
-
-
?
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
Staphylococcus aureus COL
-
dihydrodipicolinate + H2O
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
4.3.3.7
Staphylococcus aureus
Q5HG25
-
-
4.3.3.7
Staphylococcus aureus COL
Q5HG25
-
-
Purification (Commentary)
EC Number
Commentary
Organism
4.3.3.7
gel filtration
Staphylococcus aureus
Specific Activity [micromol/min/mg]
EC Number
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
4.3.3.7
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
Staphylococcus aureus
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
-
692356
Staphylococcus aureus
dihydrodipicolinate + H2O
-
-
-
?
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
biosynthesis of (S)-lysine and meso-diaminopimelate, compounds of bacterial cell walls
692356
Staphylococcus aureus
dihydrodipicolinate + H2O
-
-
-
?
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
-
692356
Staphylococcus aureus COL
dihydrodipicolinate + H2O
-
-
-
?
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
biosynthesis of (S)-lysine and meso-diaminopimelate, compounds of bacterial cell walls
692356
Staphylococcus aureus COL
dihydrodipicolinate + H2O
-
-
-
?
Subunits
EC Number
Subunits
Commentary
Organism
4.3.3.7
homodimer
in solution and in the crystal, gel filtration, crystallization and dynamic light scattering experiments
Staphylococcus aureus
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
4.3.3.7
8
-
assay at
Staphylococcus aureus
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
4.3.3.7
225
-
in presence of excess of substrates
Staphylococcus aureus
L-lysine
Application (protein specific)
EC Number
Application
Commentary
Organism
4.3.3.7
pharmacology
enzyme structure analysis for design of novel therapeutics against bacterial pathogen
Staphylococcus aureus
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
4.3.3.7
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
Staphylococcus aureus
Crystallization (Commentary) (protein specific)
EC Number
Crystallization
Organism
4.3.3.7
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
Staphylococcus aureus
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
4.3.3.7
225
-
in presence of excess of substrates
Staphylococcus aureus
L-lysine
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
L-lysine
poor feedback inhibition by
Staphylococcus aureus
KM Value [mM] (protein specific)
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
4.3.3.7
0.12
-
pyruvate
-
Staphylococcus aureus
4.3.3.7
0.33
-
(S)-aspartate 4-semialdehyde
-
Staphylococcus aureus
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
Staphylococcus aureus
-
dihydrodipicolinate + H2O
-
-
?
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
Staphylococcus aureus COL
-
dihydrodipicolinate + H2O
-
-
?
Purification (Commentary) (protein specific)
EC Number
Commentary
Organism
4.3.3.7
gel filtration
Staphylococcus aureus
Specific Activity [micromol/min/mg] (protein specific)
EC Number
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
4.3.3.7
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
Staphylococcus aureus
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
-
692356
Staphylococcus aureus
dihydrodipicolinate + H2O
-
-
-
?
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
biosynthesis of (S)-lysine and meso-diaminopimelate, compounds of bacterial cell walls
692356
Staphylococcus aureus
dihydrodipicolinate + H2O
-
-
-
?
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
-
692356
Staphylococcus aureus COL
dihydrodipicolinate + H2O
-
-
-
?
4.3.3.7
(S)-aspartate 4-semialdehyde + pyruvate
biosynthesis of (S)-lysine and meso-diaminopimelate, compounds of bacterial cell walls
692356
Staphylococcus aureus COL
dihydrodipicolinate + H2O
-
-
-
?
Subunits (protein specific)
EC Number
Subunits
Commentary
Organism
4.3.3.7
homodimer
in solution and in the crystal, gel filtration, crystallization and dynamic light scattering experiments
Staphylococcus aureus
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
4.3.3.7
8
-
assay at
Staphylococcus aureus