Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • McClerren, A.L.; Endsley, S.; Bowman, J.L.; Andersen, N.H.; Guan, Z.; Rudolph, J.; Raetz, C.R.
    A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin (2005), Biochemistry, 44, 16574-16583.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.5.1.108 drug development lipid A is an essential component of the outer membranes of most Gram-negative bacteria, making LpxC an attractive target for antibiotic design Escherichia coli
3.5.1.108 drug development lipid A is an essential component of the outer membranes of most Gram-negative bacteria, making LpxC an attractive target for antibiotic design Aquifex aeolicus

Protein Variants

EC Number Protein Variants Comment Organism
3.5.1.108 G17S partially-inactivated LpxC mutant G17S Escherichia coli

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.5.1.108 (3R,5R)-3-hydroxy-5-(2-(hydroxyamino)-2-oxoethyl)-2-(hydroxymethyl)tetrahydro-2H-pyran-4-yl tetradecanoate substrate-analog LpxC inhibitor, possesses little or no antibacterial activity, because it probably cannot penetrate the Gram-negative cell envelope Aquifex aeolicus
3.5.1.108 (3R,5R)-3-hydroxy-5-(2-(hydroxyamino)-2-oxoethyl)-2-(hydroxymethyl)tetrahydro-2H-pyran-4-yl tetradecanoate substrate-analog LpxC inhibitor, possesses little or no antibacterial activity, because it probably cannot penetrate the Gram-negative cell envelope Escherichia coli
3.5.1.108 (R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide
-
 Aquifex aeolicus
3.5.1.108 (R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide
-
 Escherichia coli
3.5.1.108 (S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine
-
 Aquifex aeolicus
3.5.1.108 (S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine phenyloxazoline hydroxamic acid, competitive inhibitor in Escherichia coli, not active as an antibiotic against Aquifex aeolicus, Pseudomonas aeruginosa and other clinically important pathogens Escherichia coli
3.5.1.108 Ciprofloxacin
-
 Aquifex aeolicus
3.5.1.108 Ciprofloxacin
-
 Escherichia coli
3.5.1.108 additional information (S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine, phenyloxazoline hydroxamic acid, competitive inhibitor in Escherichia coli, not active as an antibiotic against Aquifex aeolicus, Pseudomonas aeruginosa and other clinically important pathogens Aquifex aeolicus
3.5.1.108 N-((2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl)-4-((4-(morpholinomethyl)phenyl)ethynyl)benzamide N-aroyl-L-threonine hydroxamic acid, antibiotic activity comparable to ciprofloxacin, slow, tight-binding LpxC inhibitor Aquifex aeolicus
3.5.1.108 N-((2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl)-4-((4-(morpholinomethyl)phenyl)ethynyl)benzamide N-aroyl-L-threonine hydroxamic acid, antibiotic activity comparable to ciprofloxacin, slow, tight-binding LpxC inhibitor Escherichia coli
3.5.1.108 tobramycin
-
 Aquifex aeolicus
3.5.1.108 tobramycin
-
 Escherichia coli

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.5.1.108 Zn2+ dependent Escherichia coli
3.5.1.108 Zn2+ dependent Aquifex aeolicus

Organism

EC Number Organism UniProt Comment Textmining
3.5.1.108 Aquifex aeolicus
-
-
-
3.5.1.108 Escherichia coli
-
 R477
-
3.5.1.108 Escherichia coli R477
-
 R477
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.5.1.108
-
 Escherichia coli
3.5.1.108
-
 Aquifex aeolicus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.5.1.108 UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine + H2O
-
 Escherichia coli UDP-3-O-((R)-3-hydroxymyristoyl)-D-glucosamine + acetate
-
 ?
3.5.1.108 UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine + H2O
-
 Aquifex aeolicus UDP-3-O-((R)-3-hydroxymyristoyl)-D-glucosamine + acetate
-
 ?
3.5.1.108 UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine + H2O
-
 Escherichia coli R477 UDP-3-O-((R)-3-hydroxymyristoyl)-D-glucosamine + acetate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.5.1.108 LpxC
-
 Escherichia coli
3.5.1.108 LpxC
-
 Aquifex aeolicus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.5.1.108 30
-
 assay at Escherichia coli
3.5.1.108 30
-
 assay at Aquifex aeolicus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.5.1.108 7.4
-
 assay at Escherichia coli
3.5.1.108 7.4
-
 assay at Aquifex aeolicus

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
3.5.1.108 additional information
-
 (S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine Ki value is higher than 500 microM Aquifex aeolicus
3.5.1.108 0.000002
-
 N-((2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl)-4-((4-(morpholinomethyl)phenyl)ethynyl)benzamide
-
 Escherichia coli
3.5.1.108 0.000002
-
 N-((2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl)-4-((4-(morpholinomethyl)phenyl)ethynyl)benzamide
-
 Aquifex aeolicus
3.5.1.108 0.00002
-
 (R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide
-
 Escherichia coli
3.5.1.108 0.00005
-
 (S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine Escherichia coli Escherichia coli
3.5.1.108 0.00065
-
 (3R,5R)-3-hydroxy-5-(2-(hydroxyamino)-2-oxoethyl)-2-(hydroxymethyl)tetrahydro-2H-pyran-4-yl tetradecanoate pH 5.5 Aquifex aeolicus
3.5.1.108 0.00065
-
 (3R,5R)-3-hydroxy-5-(2-(hydroxyamino)-2-oxoethyl)-2-(hydroxymethyl)tetrahydro-2H-pyran-4-yl tetradecanoate Escherichia coli and Aquifex aeolicus, pH 5.5 Escherichia coli