BRENDA - Enzyme Database show

Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin

Heinemann, I.U.; Schulz, C.; Schubert, W.D.; Heinz, D.W.; Wang, Y.G.; Kobayashi, Y.; Awa, Y.; Wachi, M.; Jahn, D.; Jahn, M.; Antimicrob. Agents Chemother. 54, 267-272 (2010)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
4.2.1.24
expressed in Escherichia coli as a His-tagged fusion protein
Pseudomonas aeruginosa
Crystallization (Commentary)
EC Number
Crystallization
Organism
4.2.1.24
porphobilinogen synthase is cocrystallized with the alaremycin
Pseudomonas aeruginosa
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
4.2.1.24
alaremycin
porphobilinogen synthase is cocrystallized with the alaremycin. At 1.75 A resolution, the crystal structure reveals that the antibiotic efficiently blocks the active site of porphobilinogen synthase. The antibiotic binds as a reduced derivative of 5-acetamido-4-oxo-5-hexenoic acid. The corresponding methyl group is not coordinated by any amino acid residues of the active site, excluding its functional relevance for alaremycin inhibition. Alaremycin is covalently bound by the catalytically important active-site lysine residue 260 and is tightly coordinated by several active-site amino acids
Pseudomonas aeruginosa
KM Value [mM]
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
4.2.1.24
0.00032
-
5-aminolevulinic acid
-
Pseudomonas aeruginosa
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
4.2.1.24
Pseudomonas aeruginosa
Q59643
-
-
Purification (Commentary)
EC Number
Commentary
Organism
4.2.1.24
using affinity chromatography and anion-exchange chromatography
Pseudomonas aeruginosa
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.2.1.24
5-aminolevulinic acid + 5-aminolevulinic acid
-
701747
Pseudomonas aeruginosa
porphobilinogen + 2 H2O
-
-
-
?
Turnover Number [1/s]
EC Number
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
4.2.1.24
16.1
-
5-aminolevulinic acid
-
Pseudomonas aeruginosa
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
4.2.1.24
1.33
-
alaremycin
-
Pseudomonas aeruginosa
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
4.2.1.24
1.33
-
-
Pseudomonas aeruginosa
alaremycin
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
4.2.1.24
expressed in Escherichia coli as a His-tagged fusion protein
Pseudomonas aeruginosa
Crystallization (Commentary) (protein specific)
EC Number
Crystallization
Organism
4.2.1.24
porphobilinogen synthase is cocrystallized with the alaremycin
Pseudomonas aeruginosa
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
4.2.1.24
1.33
-
-
Pseudomonas aeruginosa
alaremycin
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
4.2.1.24
alaremycin
porphobilinogen synthase is cocrystallized with the alaremycin. At 1.75 A resolution, the crystal structure reveals that the antibiotic efficiently blocks the active site of porphobilinogen synthase. The antibiotic binds as a reduced derivative of 5-acetamido-4-oxo-5-hexenoic acid. The corresponding methyl group is not coordinated by any amino acid residues of the active site, excluding its functional relevance for alaremycin inhibition. Alaremycin is covalently bound by the catalytically important active-site lysine residue 260 and is tightly coordinated by several active-site amino acids
Pseudomonas aeruginosa
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
4.2.1.24
1.33
-
alaremycin
-
Pseudomonas aeruginosa
KM Value [mM] (protein specific)
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
4.2.1.24
0.00032
-
5-aminolevulinic acid
-
Pseudomonas aeruginosa
Purification (Commentary) (protein specific)
EC Number
Commentary
Organism
4.2.1.24
using affinity chromatography and anion-exchange chromatography
Pseudomonas aeruginosa
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.2.1.24
5-aminolevulinic acid + 5-aminolevulinic acid
-
701747
Pseudomonas aeruginosa
porphobilinogen + 2 H2O
-
-
-
?
Turnover Number [1/s] (protein specific)
EC Number
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
4.2.1.24
16.1
-
5-aminolevulinic acid
-
Pseudomonas aeruginosa
KCat/KM [mM/s]
EC Number
kcat/KM Value [1/mMs-1]
kcat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
4.2.1.24
50300
-
5-aminolevulinic acid
-
Pseudomonas aeruginosa
KCat/KM [mM/s] (protein specific)
EC Number
KCat/KM Value [1/mMs-1]
KCat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
4.2.1.24
50300
-
5-aminolevulinic acid
-
Pseudomonas aeruginosa