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Literature summary for 3.5.1.108 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
Search for more literature for 3.5.1.108

Application

Application Comment Organism
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
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

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

Inhibitors

Inhibitors Comment Organism Structure
(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
(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
(R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide
-
 Aquifex aeolicus
(R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide
-
 Escherichia coli
(S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine
-
 Aquifex aeolicus
(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
Ciprofloxacin
-
 Aquifex aeolicus
Ciprofloxacin
-
 Escherichia coli
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
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
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
tobramycin
-
 Aquifex aeolicus
tobramycin
-
 Escherichia coli

Metals/Ions

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

Organism

Organism UniProt Comment Textmining
Aquifex aeolicus
-
-
-
Escherichia coli
-
 R477
-
Escherichia coli R477
-
 R477
-

Purification (Commentary)

Purification (Comment) Organism
-
 Escherichia coli
-
 Aquifex aeolicus

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
LpxC
-
 Escherichia coli
LpxC
-
 Aquifex aeolicus

Temperature Optimum [°C]

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

pH Optimum

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

Ki Value [mM]

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