Literature summary for 3.5.1.108 extracted from

Gao, N.; McLeod, S.; Hajec, L.; Olivier, N.; Lahiri, S.; Prince, D.; Thresher, J.; Ross, P.; Whiteaker, J.; Doig, P.; Li, A.; Hill, P.; Cornebise, M.; Reck, F.; Hale, M.
Overexpression of Pseudomonas aeruginosa LpxC with its inhibitors in an acrB-deficient Escherichia coli strain (2014), Protein Expr. Purif., 104, 57-64.

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Application

Application	Comment	Organism
drug development	the enzyme is a target for antibiotic therapy and structure-based drug design	Pseudomonas aeruginosa
pharmacology	the enzyme is a target for antibiotic therapy and structure-based drug design	Pseudomonas aeruginosa

Cloned(Commentary)

Cloned (Comment)	Organism
gene envA or lpxC, functional overexpression of the first 299 amino acids out of 303 of enzyme mutant C40S in an Escherichia coli strain BL21(DE3) pLysS, and with its inhibitors in the acrB-deficient variant strain BL21(DE3) DELTAacrB pLysS or ARC5329	Pseudomonas aeruginosa

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant truncated enzyme mutant C40S in complex with inhibitor B, sitting drop vapor diffusion method, 2 days to 4 months, X-ray diffraction structure determination and analysis at 2.06 A resolution, molecular replacement, LpxC binding to the inhibitor increases protein solubility, shortens crystallization time and leads to a high-resolution crystal structure, to reduce the amount of compound needed, an overexpression strain of Escherichia coli is created lacking acrB, a critical component of the major efflux pump	Pseudomonas aeruginosa

Crystallization (Comment)

Organism

purified recombinant truncated enzyme mutant C40S in complex with inhibitor B, sitting drop vapor diffusion method, 2 days to 4 months, X-ray diffraction structure determination and analysis at 2.06 A resolution, molecular replacement, LpxC binding to the inhibitor increases protein solubility, shortens crystallization time and leads to a high-resolution crystal structure, to reduce the amount of compound needed, an overexpression strain of Escherichia coli is created lacking acrB, a critical component of the major efflux pump

Pseudomonas aeruginosa

Protein Variants

Protein Variants	Comment	Organism
C40S	site-directed mutagenesis, crystal structure analysis	Pseudomonas aeruginosa
additional information	LpxC binding to the inhibitor increases protein solubility, shortens crystallization time and leads to a high-resolution crystal structure, to reduce the amount of compound needed, an overexpression strain of Escherichia coli is created lacking acrB, a critical component of the major efflux pump	Pseudomonas aeruginosa

Inhibitors

Inhibitors	Comment	Organism
(2R)-N-hydroxy-2-(methanesulfonyl)-2-methyl-4-(4-oxo-7-phenylquinazolin-3(4H)-yl)butanamide	-	Pseudomonas aeruginosa
6-(1H-benzimidazol-1-yl)-N-hydroxy-5-[4-([6-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl]ethynyl)phenyl]pyridine-3-carboxamide	crystal structure of inhibitor B bound to the enzyme	Pseudomonas aeruginosa
additional information	structure-based drug design, inhibitor binding structures, overview	Pseudomonas aeruginosa
N-hydroxy-6-(1H-imidazol-1-yl)-5-[4-([6-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl]ethynyl)phenyl]pyridine-3-carboxamide	-	Pseudomonas aeruginosa
N-[(2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl]-4-([6-[(morpholin-4-yl)methyl]pyridin-3-yl]ethynyl)benzamide	-	Pseudomonas aeruginosa

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Zn2+	zinc-dependent metalloamidase, binding structure analysis from crystal structure	Pseudomonas aeruginosa

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
29000	-	recombinant enzyme, gel filtration	Pseudomonas aeruginosa
33107	-	1 * 33107, recombinant enzyme, mass spectrometry	Pseudomonas aeruginosa

Organism

Organism	UniProt	Comment	Textmining
Pseudomonas aeruginosa	P47205	gene envA or lpxC	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant truncated enzyme mutant C40S from Escherichia coli by anion exchange and hydrophobic interaction chromatography, ultrafiltration, and gel filtration. The inhibitors remain bound to LpxC throughout purification	Pseudomonas aeruginosa

Subunits

Subunits	Comment	Organism
monomer	1 * 33107, recombinant enzyme, mass spectrometry	Pseudomonas aeruginosa

Synonyms

Synonyms	Comment	Organism
LpxC	-	Pseudomonas aeruginosa
UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase	-	Pseudomonas aeruginosa

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.00000023	-	pH and temperature not specified in the publication	Pseudomonas aeruginosa	(2R)-N-hydroxy-2-(methanesulfonyl)-2-methyl-4-(4-oxo-7-phenylquinazolin-3(4H)-yl)butanamide
0.00000048	-	pH and temperature not specified in the publication	Pseudomonas aeruginosa	6-(1H-benzimidazol-1-yl)-N-hydroxy-5-[4-([6-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl]ethynyl)phenyl]pyridine-3-carboxamide
0.00000063	-	pH and temperature not specified in the publication	Pseudomonas aeruginosa	N-[(2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl]-4-([6-[(morpholin-4-yl)methyl]pyridin-3-yl]ethynyl)benzamide
0.00000064	-	pH and temperature not specified in the publication	Pseudomonas aeruginosa	N-hydroxy-6-(1H-imidazol-1-yl)-5-[4-([6-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl]ethynyl)phenyl]pyridine-3-carboxamide

General Information

General Information	Comment	Organism
metabolism	the enzyme catalyzes the first committed step of biosynthesis of lipid A	Pseudomonas aeruginosa