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Information on EC 2.7.8.43 - lipid A phosphoethanolamine transferase and Organism(s) Escherichia coli and UniProt Accession P75785
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2.7.8.43 lipid A phosphoethanolamine transferaseIUBMB Comments
The enzyme adds one or two ethanolamine phosphate groups to lipid A giving a diphosphate, sometimes in combination with EC 2.4.2.43 (lipid IVA 4-amino-4-deoxy-L-arabinosyltransferase) giving products with 4-amino-4-deoxy-beta-L-arabinose groups at the phosphates of lipid A instead of diphosphoethanolamine groups. It will also act on lipid IVA and Kdo2-lipid A.
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Word Map
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
phosphoethanolamine transferase, petn transferase, pea transferase, lipid a phosphoethanolamine transferase, cj0256, esa_rs09200, lpt-o, lipooligosaccharide phosphoethanolamine transferase a, hp0022, eptapa, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EptA
lipid A PEA transferase
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LptA
PmrA
LptA
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PmrA
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SYSTEMATIC NAME
IUBMB Comments
diacylphosphatidylethanolamine:lipid-A phosphoethanolaminetransferase
The enzyme adds one or two ethanolamine phosphate groups to lipid A giving a diphosphate, sometimes in combination with EC 2.4.2.43 (lipid IVA 4-amino-4-deoxy-L-arabinosyltransferase) giving products with 4-amino-4-deoxy-beta-L-arabinose groups at the phosphates of lipid A instead of diphosphoethanolamine groups. It will also act on lipid IVA and Kdo2-lipid A.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
diacylphosphatidylethanolamine + arbutin
diacylglycerol + ?
arbutin is a substrate for the phosphoethanolamine transferase
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?
diacylphosphatidylethanolamine + lipid A
diacylglycerol + lipid A 1-(2-aminoethyl diphosphate)
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?
diacylphosphatidylethanolamine + lipid A
diacylglycerol + lipid A 4'-(2-aminoethyl diphosphate)
diacylphosphatidylethanolamine + lipid A
diacylglycerol + lipid A 4'-(2-aminoethyl diphosphate)
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?
diacylphosphatidylethanolamine + lipid A
diacylglycerol + lipid A 4'-(2-aminoethyl diphosphate)
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?
additional information
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the phosphoethanolamine cycle, overview
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?
additional information
?
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enzyme EptA or PmrC catalyses the periplasmic addition of the positively charged substituent phosphoethanolamine to lipid A controlled by the PmrA transcriptional regulator and conferring resistance to cationic antimicrobial peptides, including polymyxin
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?
additional information
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quantitative analysis of binding of LPS by LptA, 1:1 ratio for the LPS:LptA complex, and structure analysis of the LPS binding pocket. The entire LptA protein is affected by LPS binding, the N-terminus unfolds in the presence of LPS
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?
additional information
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specific LPS interactions with LptA and LptC
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?
additional information
?
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transfer may occur both to the 4'- and 1-phospho groups of lipid A
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
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the phosphoethanolamine cycle, overview
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe3+
required, the peptA (eptA promoter) is induced sevenfold in the presence of Fe3+
Zn2+
a zinc ion is present at a conserved site in addition to three zincs more peripherally located in the active site
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
LpxT
role for LpxT in the reduction of enzyme EptA activity, the transcriptional regulation of lpxT gene is PmrA-independent. PmrA-dependent inhibition of LpxT is required for phosphoethanolamine decoration of lipid A
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
arbutin
arbutin is also a substrate for phosphoethanolamine transferase stimulating its activity, increasing phosphatidylethanolamine turnover leading to accumulation of diacylglycerol toxic for bacteria
PmrA
te enzyme EptA is activated in a PmrA-dependent manner, overview
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the enzyme is located on the periplasmic side of the inner membrane
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LptA is the only component of the Lpt system that lacks a transmembrane component, as it spans the periplasmic space between the inner membrane and outer membrane complexes. LptA is bound to other Lpt components rather than floating freely in the periplasm
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possibly one or more LptA proteins bridges the periplasm to form a large, connected protein complex
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
the enzyme is required for substitution of osmoregulated periplasmic glucans by phosphoethanolamine
evolution
LptA is a member of the lipopolysaccharide transport protein (Lpt) family
malfunction
metabolism
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the polymyxin-resistant phenotype is primarily under the control of the PmrA/PmrB two-component regulatory system that is activated during growth under conditions of low pH, high Fe3+, and in a PhoP/PhoQ-dependent manner during Mg2+ starvation
physiological function
malfunction
eptA mutants show a 20fold decrease in polymyxin B resistanc. Overexpression of LpxT in trans in Escherichia coli strain WD101 results in loss of phosphoethanolamine modification and compromised WD101 polymyxin resistance
malfunction
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WD101, a polymyxin-resistant Escherichia coli K-12 strain, contains a mutation in the pmrA (basR) gene resulting in a pmrAC phenotype promoting polymyxin resistance
malfunction
a mutant LptA protein unable to form oligomers has an altered affinity for LPS
physiological function
EptA-dependent lipid A modification is required for resistance to polymyxin B, EptA plays a dominant role in polymyxin resistance. Enzyme PmrA is not involved in transcription of LpxT, which catalyses the phosphorylation of lipid A at the 1-position forming 1-diphosphate lipid A increasing the negative charge of the bacterial surface. LpxT-dependent lipid A modification is regulated post-translationally. The regulation does not occur at the level of transcription, but rather following the assembly of LpxT into the inner membrane. PmrA-dependent inhibition of LpxT is required for phosphoethanolamine decoration of lipid A, which is critical for Escherichia coli to resist the bactericidal activity of polymyxin
physiological function
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the enzyme regulates the modification of phosphate moieties of lipid A, which may be substituted with L-4-aminoarabinose or phosphoethanolamine groups. The enzyme also regulates the catalysis of periplasmic addition of L-4-aminoarabinose to lipid A through glycosyltransferase L-4-aminoarabinose transferase (ArnT)
physiological function
LptA functions to transport lipopolysaccharide (LPS) through the periplasm to the outer leaflet of the outer membrane after ABC transporter MsbA flips LPS across the inner membrane. It is hypothesized that LPS binds to LptA to cross the periplasm and that the acyl chains of LPS bind to the central pocket of LptA
physiological function
the LPS (lipopolysaccharide) transport (Lpt) system, a coordinated seven-subunit protein complex that spans the cellular envelope. LPS transport is driven by an ATPase-dependent mechanism dubbed the PEZ model, whereby a continuous stream of LPS molecules is pushed from subunit to subunit, functional significance of LptA oligomerization and LptC. The membrane-bound LptB, F, G and C subunits are connected to the LptD/E heterodimer in the outer membrane by periplasmic LptA. The LptB2FG tetramer extracts LPS from the outer leaflet of the inner membrane and provides the energy to drive LPS transport through an ATPase-dependent mechanism. LptA provides a continuous LPS binding surface that conveys it to the outer membrane. Mechanism of the LPS (lipopolysaccharide) transport (Lpt) system, specific LPS interactions with LptA and LptC, LptC is the intermediate between the inner membrane complex and LptA, overview
physiological function
a 6-residue-requiring zinc-binding/catalytic motif is essential for MCR2-mediated colistin resistance. The transmembrane regions TM2 and TM1 play a critical role in MCR2-mediated colistin resistance, catalytic activity depends on the correct location of MCR2 in bacterial periplasm
physiological function
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minimum inhibitory concentrations of polymyxin B and colistin for the wild-type are twice as high as those for the mutant lacking the eptA gene
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oligomer
the enzyme LptA arranges in an end-to-end fibrous tetramer, which forms a continuous hydrophobic groove between the LptA monomers, crystal structure analysis. Mass spectral analysis confirmes that LptA forms 2-5-member oligomers in a concentration-dependent manner when purified in vitro and that the resultant complexes are stabilized by LPS. Analysis of subunit interactions
additional information
according to light scattering data, LptA oligomerizes in a concentration-dependent manner. LptA is an average of a trimer in solution, and a considerably higher order oligomerization state (25mers) is predicted at a protein concentration of 0.1 mM
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structure of the catalytic domain ofMCR1 at 1.32 A resolution. The putative nucleophile for catalysis, threonine 285, is phosphorylated in MCR1 and a zinc is present at a conserved site in addition to three zincs more peripherally located in the active site. Binding sites for the lipid A and phosphatidylethanolamine substrates are not apparent in the MCR1 structure
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D463A
mutant cannot confer robust growth to the recipient strain in presence of more than 2 mg/liter of colistin
E244A
mutant cannot confer robust growth to the recipient strain in presence of more than 2 mg/liter of colistin
H393A
mutant cannot confer robust growth to the recipient strain in presence of more than 2 mg/liter of colistin
H464A
mutant cannot confer robust growth to the recipient strain in presence of more than 2 mg/liter of colistin
H476A
mutant cannot confer robust growth to the recipient strain in presence of more than 2 mg/liter of colistin
I36R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
I36R1/Q148A/K149A
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
I86R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
I86R1/Q148A/K149A
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
L145R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
L45R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
M98R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
N185R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
N185R1/Q148A/K149A
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
Q148A/K149A
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
S110R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
T283A
mutant cannot confer robust growth to the recipient strain in presence of more than 2 mg/liter of colistin
T32R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
V132R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
V165R1
site-directed mutagenesis, altered lipopolysaccharide binding kinetics compared to wild-type
additional information
additional information
construction of the opgE::cml mutant, and of the opgE::Tn5 mutant by random transposon mutagenesis with Tn5
additional information
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construction of the opgE::cml mutant, and of the opgE::Tn5 mutant by random transposon mutagenesis with Tn5
additional information
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generation of polymyxin-sensitive mutants of an Escherichia coli pmrAC strain WD101 producing a lipid A that lacked both the 3'-acyloxyacyl-linked myristate (C14) and L-4-aminoarabinose, even though the necessary enzymatic machinery required to synthesize L-4-aminoarabinose-modified lipid A is present. Strain WD103 is generated by P1vir transduction of the polymyxin-resistant genotype (pmrAC) of strain WD101 into the Escherichia coli lpxM mutant MLK1067, phenotype, overview. The polymyxin-sensitive parent strains MLK1067 and W3110 produce unmodified penta- or hexa-acylated lipid A, respectively. Complementation of WD103 with the vector pWSLpxM resulted in restoration of polymyxin resistance to the levels displayed by WD101, effect of lipid myristoylation on the polymyxin resistance
additional information
domain swapping between isoforms Mcr1 and Mcr2 shows that the presence of the resultant two chimeric genes can confer resistance of the colistin-susceptible strain MG1655 to up to 16 mg/liter of colistin
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3)pLysS by cobalt affinity chromatography, dialysis, and ultrafiltration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
genetic screening identifies gene opgE, DNA and amino acid sequence determination and analysis, genetic organization of opg genes in Escherichia coli, overview. The gene is transformed into competent Escherichia coli cells to give pNF752
gene lptA, recombinant expression of C-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)pLysS
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the peptA (eptA promoter) is induced sevenfold in the presence of Fe3+, induction is lost in enzyme mutant strain CH020 (DELTApmrA)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Herrera, C.M.; Hankins, J.V.; Trent, M.S.
Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides
Mol. Microbiol.
76
1444-1460
2010
Escherichia coli (P30845), Salmonella enterica (P36555), Salmonella enterica LT2 (P36555)
Tran, A.X.; Lester, M.E.; Stead, C.M.; Raetz, C.R.; Maskell, D.J.; McGrath, S.C.; Cotter, R.J.; Trent, M.S.
Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A
J. Biol. Chem.
280
28186-28194
2005
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium, Salmonella enterica subsp. enterica serovar Typhimurium C5
Bontemps-Gallo, S.; Cogez, V.; Robbe-Masselot, C.; Quintard, K.; Dondeyne, J.; Madec, E.; Lacroix, J.M.
Biosynthesis of osmoregulated periplasmic glucans in Escherichia coli: the phosphoethanolamine transferase is encoded by opgE
BioMed Res. Int.
2013
371429
2013
Escherichia coli (P75785), Escherichia coli
Hicks, G.; Jia, Z.
Structural basis for the lipopolysaccharide export activity of the bacterial lipopolysaccharide transport system
Int. J. Mol. Sci.
19
E2680
2018
Escherichia coli (P0ADV1)
Schultz, K.M.; Lundquist, T.J.; Klug, C.S.
Lipopolysaccharide binding to the periplasmic protein LptA
Protein Sci.
26
1517-1523
2017
Escherichia coli (P0ADV1)
Stojanoski, V.; Sankaran, B.; Prasad, B.V.V.; Poirel, L.; Nordmann, P.; Palzkill, T.
Structure of the catalytic domain of the colistin resistance enzyme MCR-1
BMC Biol.
14
81
2016
Escherichia coli (A0A0R6L508)
Sun, J.; Xu, Y.; Gao, R.; Lin, J.; Wei, W.; Srinivas, S.; Li, D.; Yang, R.-S.; Li, X.-P.; Liao, X.-P.; Liu, Y.-H.; Feng, Y.
Deciphering MCR-2 colistin resistance
mBio
8
e00625
2017
Escherichia coli (A0A1C3NEV1)
Jo, S.; Park, H.; Song, W.; Kim, S.; Kim, E.; Yang, Y.; Kim, J.; Kim, B.; Kim, Y.
Structural characterization of phosphoethanolamine-modified lipid A from probiotic Escherichia coli strain Nissle 1917
RSC Adv.
9
19762-19771
2019
Escherichia coli, Escherichia coli Nissle 1917
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