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(3R)-3-hydroxyarachidonoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2-N-((3R)-3-hydroxyarachidonoyl)-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
the external layer of the Gram-negative bacterial outer membrane is primarily composed of a protective, selectively permeable lipopolysaccharide. The biosynthesis of lipopolysaccharide relies on UDP-3-O-acyl-glucosamine N-acyltransferase (LpxD), which transfers 3-hydroxy-arachidonic acid from acyl carrier protein to the 2' amine of UDP-3-O-myristoyl glucosamine. CtLpxD is expected to utilize R-3-hydroxyarachidonoyl-[acyl-carrier protein] and UDP-3-O-(myristoyl)-R-D-glucosamine, based on the predominant molecular species of Chlamydia trachomatis lipid A. This proposal is not validated by in vitro assays
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis(3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
(R,S)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
wild-type LpxD prefers (R,S)-3-hydroxymyristoyl-[acyl-carrier protein] over (R,S)-3-hydroxypalmitoyl-[acyl-carrier protein] by a factor of 3, whereas the M290A mutant has the opposite selectivity
-
-
?
(R,S)-3-hydroxypalmitoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
wild-type LpxD prefers (R,S)-3-hydroxymyristoyl-[acyl-carrier protein] over (R,S)-3-hydroxypalmitoyl-[acyl-carrier protein] by a factor of 3, whereas the M290A mutant has the opposite selectivity
-
-
?
additional information
?
-
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
-
since only (R)-3-hydroxymyristate is found at the 2,3,2, and 3 positions of Escherichia coli lipid A, it is reassuring that both Escherichia coli acyltransferases display extraordinary specificity for (R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
-
myristoyl-[acyl-carrier protein] does not serve as an acyl donor for the overproduced UDP-3-O-((R)-3-hydroxymyristoyl)-GlcN N-acyltransferase
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
a comparison of the lipid A structures shows that in Escherichia coli and Neisseria meningitidis, LpxD can be expected to have the same specificity, both adding 3-hydroxymyristoyl chains
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis(3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
-
third step of lipid A biosynthesis
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis(3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
-
compulsory ordered mechanism in which (3R)-3-hydroxymyristoyl-[acyl-carrier protein] binds prior to UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine. The product, UDP-2,3-diacylglucosamine, dissociates prior to acyl-carrier protein
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
the LpxD1 enzyme adds a 3-OH C18 acyl group at 37 °C (host), whereas the LpxD2 enzyme adds a 3-OH C16 acyl group at 18 °C (environment)
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
the LpxD1 enzyme adds a 3-OH C18 acyl group at 37 °C (host), whereas the LpxD2 enzyme adds a 3-OH C16 acyl group at 18 °C (environment)
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-
ir
additional information
?
-
His247 and His284 contribute to a mechanism involving nucleophilic attack by the amine of one substrate on the carbonyl carbon of an acyl carrier protein thioester conjugate
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-
?
additional information
?
-
-
His247 and His284 contribute to a mechanism involving nucleophilic attack by the amine of one substrate on the carbonyl carbon of an acyl carrier protein thioester conjugate
-
-
?
additional information
?
-
-
both LpxA and LpxD, from Escherichia coli are also able to incorporate odd-chain fatty acids into lipid A when grown in the presence of 1% propionic acid. When grown on 1% propionic acid lipid A also contains the odd-chain fatty acids tridecanoic acid (C13), pentadecanoic acid (C15), hydroxy tridecanoic acid (C13OH), and hydroxy pentadecanoic acid (C15OH). Escherichia coli lipid A acyltransferases do not have an absolute specificity for 14-carbon hydroxy fatty acids but can transfer fatty acids differing by one carbon unit if the fatty acid substrates are available
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-
?
additional information
?
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-
R-3-hydroxylauroyl-methylphosphopantetheine is a very poor substrate. The specific activity, measured at either 0.01 mM or 1 mM (3R)-3-hydroxylauroylmethylphosphopantetheine as the acyl donor, is more than 100fold lower than with 0.01 mM (3R)-3-hydroxymyristoyl-[acyl-carrier protein]
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-
?
additional information
?
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-
fluorescent enzyme assay, method optimization, overview
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-
?
additional information
?
-
ordered-sequential reaction mechanism. Acyl-ACP binds first to free LpxD forming a binary complex. ACP associates with the ACP-recognition domain and the acyl-4'-phosphopantetheine group packs into the hydrophobic N-channel. UDP-acyl-GlcN binds next, which initiates acyl transfer. In the ternary product complex, the 4'-phosphopantetheine arm of hydrolysed-acyl-ACP completely encloses the reaction chamber, blocking UDP-diacyl-GlcN from leaving. By moving the 4'-phosphopantetheine group towards Met 290, the catalytic chamber opens up. This motion drives the eventual release of UDP-diacyl-GlcN and triggers conformational changes downstream of helix-II leading to holo-ACP dissociation
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-
?
additional information
?
-
-
lipid A from strains expressing either of the Porphyromonas gingivalis transferases contains 16-carbon hydroxy fatty acids in addition to the normal Escherichia coli 14-carbon hydroxy fatty acids, demonstrating that these acyltransferases display a relaxed acyl chain length specificity. Both LpxA and LpxD, from either Escherichia coli or Porphyromonas gingivalis are also able to incorporate odd-chain fatty acids into lipid A when grown in the presence of 1% propionic acid. The relaxed specificity of the Porphyromonas gingivalis lipid A acyltransferases and the substrate availability account for the lipid A structural clusters that differ by 14 mass units observed in Porphyromonas gingivalis lipopolysaccharide preparations
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-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(3R)-3-hydroxyarachidonoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2-N-((3R)-3-hydroxyarachidonoyl)-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
the external layer of the Gram-negative bacterial outer membrane is primarily composed of a protective, selectively permeable lipopolysaccharide. The biosynthesis of lipopolysaccharide relies on UDP-3-O-acyl-glucosamine N-acyltransferase (LpxD), which transfers 3-hydroxy-arachidonic acid from acyl carrier protein to the 2' amine of UDP-3-O-myristoyl glucosamine. CtLpxD is expected to utilize R-3-hydroxyarachidonoyl-[acyl-carrier protein] and UDP-3-O-(myristoyl)-R-D-glucosamine, based on the predominant molecular species of Chlamydia trachomatis lipid A. This proposal is not validated by in vitro assays
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis(3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
-
third step of lipid A biosynthesis
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
-
since only (R)-3-hydroxymyristate is found at the 2,3,2, and 3 positions of Escherichia coli lipid A, it is reassuring that both Escherichia coli acyltransferases display extraordinary specificity for (R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
UDP-2,3-bis((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine + holo-[acyl-carrier protein]
a comparison of the lipid A structures shows that in Escherichia coli and Neisseria meningitidis, LpxD can be expected to have the same specificity, both adding 3-hydroxymyristoyl chains
-
-
?
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
-
ir
(3R)-3-hydroxymyristoyl-[acyl-carrier protein] + UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
UDP-2,3-bis[O-(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine + a holo-[acyl-carrier protein]
-
-
-
-
ir
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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0.0017 - 0.074
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
0.00084 - 0.073
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
0.004 - 0.012
UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
-
pH 8.0, 25°C, recombinant His6-tagged LpxD
additional information
additional information
-
steady-state kinetic analysis
-
0.0017
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme H276A
0.0019
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 8.0, 30°C
0.0032
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, wild-type enzyme
0.0034
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme H239A
0.0035
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme F41A
0.0038
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme K194A
0.005
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme Y47A
0.012
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme K46A
0.013
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme N233A
0.013
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme Q236A
0.047
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme D232A
0.074
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme R293A
0.00084
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme H239A
0.0013
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 8.0, 30°C
0.0036
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme R293A
0.0042
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme Q236A
0.0056
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme K194A
0.0063
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme H276A
0.0071
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme K46A
0.0078
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme Y47A
0.028
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme N233A
0.067
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme D232A
0.073
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme F41A
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.032 - 23
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
0.032 - 23
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
3
UDP-3-O-[(3R)-3-hydroxymyristoyl]-alpha-D-glucosamine
-
pH 8.0, 25°C, recombinant His6-tagged LpxD
additional information
additional information
-
steady-state kinetic analysis
-
0.032
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme H239A
0.73
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme H276A
1.4
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme N233A
1.9
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme D232A
4.1
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme F41A
5.7
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme K194A
8.9
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme R293A
12
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme Q236A
17
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme K46A
18
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme Y47A
23
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, wild-type enzyme
0.032
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme H239A
0.73
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme H276A
1.4
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme N233A
1.9
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme D232A
4.1
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme F41A
5.7
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme K194A
8.9
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme R293A
12
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme Q236A
17
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme K46A
18
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, mutant enzyme Y47A
23
UDP-3-O-((3R)-3-hydroxymyristoyl)-alpha-D-glucosamine
-
pH 7.5, 30°C, wild-type enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
9.4 - 7188
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
9.4
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme H239A
10.7
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme N233A
40.4
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme D232A
120.3
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme R293A
429
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme H276A
923
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme Q236A
1171
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme F41A
1417
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme K46A
1500
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme K194A
3600
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, mutant enzyme Y47A
7188
(3R)-3-hydroxymyristoyl-[acyl-carrier protein]
-
pH 7.5, 30°C, wild-type enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
malfunction
-
enzyme activity of the temperature-sensitive firA mutant RL-25 is reduced to less than 10% of wild-type enzyme
malfunction
-
lpxD mutant is susceptible to vancomycin and teicoplanin
malfunction
-
the lpxD1-null mutant is attenuated in C57BL/6 mice and subsequently exhibits protection against a lethal wild-type challenge. The lpxD1-null and lpxD2-null mutant strains show altered antibiotic susceptibility patterns, membrane permeability, but no innate immune responses. The DELTAlpxD1 mutant is more susceptible to antibiotics with diverse mechanisms of action such as chloramphenicol, carbenicillin, ciprofloxacin, erythromycin, rifampin, and vancomycin, whereas the DELTAlpxD2 mutant is only susceptible to carbenicillin and erythromycin
malfunction
-
lpxD1-null mutant with shorter acyl chains in lipid A is more sensitive to various environmental stresses than Francisella novicida and lpxD2-null mutant
malfunction
-
the lpxD1-null mutant is attenuated in C57BL/6 mice and subsequently exhibits protection against a lethal wild-type challenge. The lpxD1-null and lpxD2-null mutant strains show altered antibiotic susceptibility patterns, membrane permeability, but no innate immune responses. The DELTAlpxD1 mutant is more susceptible to antibiotics with diverse mechanisms of action such as chloramphenicol, carbenicillin, ciprofloxacin, erythromycin, rifampin, and vancomycin, whereas the DELTAlpxD2 mutant is only susceptible to carbenicillin and erythromycin
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metabolism
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Francisella modifies its lipid A structure in response to temperature adaptation by altering the length of the amidelinked acyl chains: 3-OH-C16 at environmental temperature and 3-OH-C18 at mammalian temperature
metabolism
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LpxD catalyzes the third step of lipid A biosynthesis, an acyl-acyl carrier protein (ACP)-dependent transfer of a fatty acyl moiety to a UDP-glucosamine core ring, overview
metabolism
the enzyme is involved in the lipid A biosynthesis in the plant
metabolism
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quantitative model of the nine enzyme-catalyzed steps of Escherichia coli lipid A biosynthesis. Biosynthesis regulation occurs through regulated degradation of the LpxC and WaaA enzymes. LpxC, EC 3.5.1.108, is the rate-limiting enzyme if pathway regulation is ignored, but LpxK, EC 2.7.1.130, is the rate-limiting enzyme if pathway regulation is present, as it is in real cells
metabolism
-
the enzyme is involved in lipid A biosynthesis
metabolism
the enzyme is involved in lipid A biosynthesis in Gram-negative bacteria
metabolism
-
Francisella modifies its lipid A structure in response to temperature adaptation by altering the length of the amidelinked acyl chains: 3-OH-C16 at environmental temperature and 3-OH-C18 at mammalian temperature
-
metabolism
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the enzyme is involved in the lipid A biosynthesis in the plant
-
physiological function
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functional LpxD is essential for bacterial viability, transcriptional control of the lpxD genes, encoding the lipid A-modifying N-acyltransferase enzymes LpxD1/2,and posttranslational control of the LpxD1 and LpxD2 enzymatic activities are involved in the mechanism for temperature-regulated membrane remodeling by LPS/lipid A-level modifications resulting in alterations of membrane fluidity, as well as integrity, that may represent a general paradigm for bacterial membrane adaptation and virulence-state adaptation
physiological function
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LpxD is essential for survival in Gram-negative bacteria
physiological function
LpxD is part of the biosynthesis pathway of lipid A and is responsible for transferring 3-hydroxymyristic acid from the R-3-hydroxymyristoyl-acyl carrier protein to the 2-OH group of UDP-3-O-(3-hydroxymyristoyl) glucosamine. The first three enzymes responsible for Gram-negative bacterial cell-wall synthesis, LpxA, LpxC and LpxD, are all present as single copies and are essential for bacterial viability
physiological function
a loss-of-expression mutant of lpxD is defective for biofilm formation on biotic and abiotic surfaces. The mutant strain exhibits significantly decreased bacterial attachment to cultured airway epithelial cells, as well as increased bacterial cytotoxicity toward airway cells. Airway cells incubated with the lpxD mutant or with mutant lipid A extracts exhibit decreased IL-8 production and necrosis, respectively
physiological function
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inactivation of isoform la0512/LpxD1, imparts sensitivity to the host physiological temperature (37°C) and renders the bacteria avirulent in an animal infection model. The LpxD1 mutant displays compromised outer membrane integrity at host physiological temperature, but only minor changes in the lipid A moiety compared to that found in the wild-type strain. An in trans complementation restores the phenotypes to a level comparable to that of the wild-type strain
physiological function
overexpression of UDP-3-O-[3-hydroxylauroyl] glucosamine N-acyltransferase reduces the quorum sensing regulator LasR activity, swarming motility, protease production and virulence without any influence on growth. These effects by PA3646 overexpression are caused by decreased production of quorum sensing signal
physiological function
-
functional LpxD is essential for bacterial viability, transcriptional control of the lpxD genes, encoding the lipid A-modifying N-acyltransferase enzymes LpxD1/2,and posttranslational control of the LpxD1 and LpxD2 enzymatic activities are involved in the mechanism for temperature-regulated membrane remodeling by LPS/lipid A-level modifications resulting in alterations of membrane fluidity, as well as integrity, that may represent a general paradigm for bacterial membrane adaptation and virulence-state adaptation
-
physiological function
-
inactivation of isoform la0512/LpxD1, imparts sensitivity to the host physiological temperature (37°C) and renders the bacteria avirulent in an animal infection model. The LpxD1 mutant displays compromised outer membrane integrity at host physiological temperature, but only minor changes in the lipid A moiety compared to that found in the wild-type strain. An in trans complementation restores the phenotypes to a level comparable to that of the wild-type strain
-
physiological function
-
a loss-of-expression mutant of lpxD is defective for biofilm formation on biotic and abiotic surfaces. The mutant strain exhibits significantly decreased bacterial attachment to cultured airway epithelial cells, as well as increased bacterial cytotoxicity toward airway cells. Airway cells incubated with the lpxD mutant or with mutant lipid A extracts exhibit decreased IL-8 production and necrosis, respectively
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D232A
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mutation causes a 10fold reduction in kcat and a striking increase in the KM for both substrates
F41A
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mutation increases the KM for UDP-3-O-((3R)-3-hydroxymyristoyl)-a-D-glucosamine 30fold and kcat 5fold
K194A
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mutation has little effect on activity
K46A
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mutation causes 3fold increase in KM((3R)-3-hydroxymyristoyl-[acyl-carrier protein]) and has no effect on kcat
M290A
wild-type EcLpxD prefers (R,S)-3-hydroxymyristoyl-ACP over (R,S)-3-hydroxypalmitoyl-ACP by a factor of 3, whereas the M290A mutant has the opposite selectivity. Both wild-type and M290A EcLpxD rescue the conditional lethality of Escherichia coli RL25, a temperature-sensitive strain harboring point mutations in lpxD. Complementation with wild-type EcLpxD restores normal lipid A containing only N-linked hydroxymyristate to RL25 at 42°C, as judged by mass spectrometry, whereas the M290A mutant generates multiple lipid A species containing one or two longer hydroxy fatty acids in place of the usual (3R)-3-hydroxymyristate at positions 2 and 20
M292A
wild-type EcLpxD prefers (R,S)-3-hydroxymyristoyl-ACP over (R,S)-3-hydroxypalmitoyl-ACP by a factor of 3, mutant enzyme M292A prefers (R,S)-3-hydroxymyristoyl-ACP over (R,S)-3-hydroxypalmitoyl-ACP by a factor of 2.5
N233A
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mutation causes a 10fold reduction in kcat and a striking increase in the KM for both substrates
N240A
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causes less than a 2fold reduction in specific activity, when assayed at substrate concentrations at 2fold above KM with the purified proteins
N44A
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causes less than a 2fold reduction in specific activity, when assayed at substrate concentrations at 2fold above KM with the purified proteins
Q236A
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mutation has little effect on activity
Q32A
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causes less than a 2fold reduction in specific activity, when assayed at substrate concentrations at 2fold above KM with the purified proteins
R293A
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KM((3R)-3-hydroxymyristoyl-[acyl-carrier protein]) increases 23fold compared to wild-type with little effect on kcat
additional information
construction of lpx insertional knockout mutations or RNAi knock-down mutants
additional information
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construction of lpx insertional knockout mutations or RNAi knock-down mutants
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additional information
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construction of lpxD1-null and lpxD2-null mutant strains, that show altered antibiotic susceptibility patterns, membrane permeability, but no innate immune responses
additional information
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construction of lpxD1-null and lpxD2-null mutant strains, that show altered antibiotic susceptibility patterns, membrane permeability, but no innate immune responses
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48
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190
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1997
Neisseria meningitidis (P95377)
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2008
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67
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2011
Pseudomonas aeruginosa (Q9HXY6)
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425
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2012
Escherichia coli
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Pathway for lipid A biosynthesis in Arabidopsis thaliana resembling that of Escherichia coli
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108
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2011
Arabidopsis thaliana (F4JGP6), Arabidopsis thaliana Col-0 (F4JGP6)
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109
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2012
Francisella tularensis subsp. novicida, Francisella tularensis subsp. novicida U112
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Structure determination of LpxD from the lipopolysaccharide-synthesis pathway of Acinetobacter baumannii
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69
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2013
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2015
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18
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2013
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83
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2015
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505
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2014
Escherichia coli (P21645)
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2014
Escherichia coli
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6
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2019
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109
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