UniProtKB - P0A725 (LPXC_ECOLI)
Protein
UDP-3-O-acyl-N-acetylglucosamine deacetylase
Gene
lpxC
Organism
Escherichia coli (strain K12)
Status
Functioni
Catalyzes the hydrolysis of UDP-3-O-myristoyl-N-acetylglucosamine to form UDP-3-O-myristoylglucosamine and acetate, the committed step in lipid A biosynthesis.UniRule annotation4 Publications
Miscellaneous
Due to its important role in lipid A synthesis, LpxC is an attractive target for the development of new antibacterial agents to treat Gram-negative infections. Many potent LpxC inhibitors with a variety of chemical scaffolds and distinct antibiotic profiles have been discovered.3 Publications
Catalytic activityi
- H2O + UDP-3-O-[(3R)-3-hydroxytetradecanoyl]-N-acetyl-α-D-glucosamine = acetate + UDP-3-O-[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamineUniRule annotation5 PublicationsEC:3.5.1.108UniRule annotation5 Publications
Cofactori
Zn2+UniRule annotation2 Publications, Fe2+2 PublicationsNote: Can use either Fe2+ or Zn2+. The metal cofactor can switch between Fe2+ and Zn2+ in response to metal availability. Metal switching may be important for regulating the LpxC activity upon changes in environmental conditions. Has a significantly higher affinity for Zn2+, but exhibits higher activity with Fe2+ (PubMed:20136146, PubMed:20709752). Can also use Co2+, Ni2+ and, to a lesser extent, Mn2+ (PubMed:10026271).3 Publications
Activity regulationi
Regulation occurs at the protein level, via degradation of LpxC by the FtsH protease (PubMed:10048027, PubMed:16420369, PubMed:21193611, PubMed:23417489). Degradation is growth rate-dependent. LpxC is degraded rapidly during slow growth, probably to avoid toxic overproduction of lipopolysaccharides, but is highly stable under optimal growth conditions (PubMed:23417489). Increased amounts of LpxC are made under conditions that reduce the lipid A content of cells (PubMed:8824222). Inhibited by metal chelators such as EDTA and dipicolinic acid (DPA) and by high concentrations of Zn2+ (PubMed:10026271).6 Publications
Kineticsi
kcat is 3.3 sec(-1) at 30 degrees Celsius. kcat is 0.09 sec(-1) at 1 degree Celsius.1 Publication
- KM=2.1 µM for UDP-3-O-myristoyl-N-acetylglucosamine (at 30 degrees Celsius)1 Publication
- KM=0.6 µM for UDP-3-O-myristoyl-N-acetylglucosamine (at 1 degree Celsius)1 Publication
: lipid IV(A) biosynthesis Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes lipid IV(A) from (3R)-3-hydroxytetradecanoyl-[acyl-carrier-protein] and UDP-N-acetyl-alpha-D-glucosamine.UniRule annotation1 PublicationProteins known to be involved in the 6 steps of the subpathway in this organism are:
- Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase (lpxA), Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase (lpxA)
- UDP-3-O-acyl-N-acetylglucosamine deacetylase (lpxC), UDP-3-O-acyl-N-acetylglucosamine deacetylase (lpxC)
- UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase (lpxD), UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase (lpxD)
- UDP-2,3-diacylglucosamine hydrolase (lpxH), UDP-2,3-diacylglucosamine hydrolase (lpxH)
- Lipid-A-disaccharide synthase (lpxB), Lipid-A-disaccharide synthase (lpxB)
- Tetraacyldisaccharide 4'-kinase (lpxK), Tetraacyldisaccharide 4'-kinase (lpxK)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes lipid IV(A) from (3R)-3-hydroxytetradecanoyl-[acyl-carrier-protein] and UDP-N-acetyl-alpha-D-glucosamine, the pathway lipid IV(A) biosynthesis and in Glycolipid biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 79 | Zinc; via tele nitrogenUniRule annotation2 Publications | 1 | |
Metal bindingi | 238 | Zinc; via tele nitrogenUniRule annotation2 Publications | 1 | |
Metal bindingi | 242 | ZincUniRule annotation2 Publications | 1 | |
Active sitei | 265 | Proton donorUniRule annotation2 Publications | 1 |
GO - Molecular functioni
- deacetylase activity Source: EcoliWiki
- iron ion binding Source: EcoCyc
- UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase activity Source: EcoCyc
- UDP-3-O-acyl-N-acetylglucosamine deacetylase activity Source: UniProtKB-EC
- zinc ion binding Source: EcoCyc
GO - Biological processi
- lipid A biosynthetic process Source: EcoliWiki
Keywordsi
Molecular function | Hydrolase |
Biological process | Lipid A biosynthesis, Lipid biosynthesis, Lipid metabolism |
Ligand | Iron, Metal-binding, Zinc |
Enzyme and pathway databases
BioCyci | EcoCyc:UDPACYLGLCNACDEACETYL-MONOMER MetaCyc:UDPACYLGLCNACDEACETYL-MONOMER |
UniPathwayi | UPA00359;UER00478 |
Chemistry databases
SwissLipidsi | SLP:000001888 |
Names & Taxonomyi
Protein namesi | Recommended name: UDP-3-O-acyl-N-acetylglucosamine deacetylase1 PublicationUniRule annotation (EC:3.5.1.108UniRule annotation5 Publications)Short name: UDP-3-O-acyl-GlcNAc deacetylase2 PublicationsUniRule annotation Alternative name(s): Protein EnvACurated UDP-3-O-[R-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase1 PublicationUniRule annotation |
Gene namesi | Name:lpxC1 PublicationUniRule annotation Synonyms:asmB1 Publication, envA1 Publication Ordered Locus Names:b0096, JW0094 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 19 | H → A: 1400-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 19 | H → Q: 90-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 19 | H → Y: 200-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 63 | C → A: Reduces level of inhibition by metal ions. 1 Publication | 1 | |
Mutagenesisi | 78 | E → A: 700-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 78 | E → Q: 3000-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 79 | H → A: 2300-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 79 | H → Q: 1200-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 238 | H → A: 1100-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 242 | D → A: 10-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 242 | D → Q: 2300-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 246 | D → A: 1800-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 265 | H → A: 3800-fold decrease in activity. 1 Publication | 1 | |
Mutagenesisi | 265 | H → Q: 5600-fold decrease in activity. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL5244 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000191929 | 1 – 305 | UDP-3-O-acyl-N-acetylglucosamine deacetylaseAdd BLAST | 305 |
Post-translational modificationi
Degraded by FtsH.4 Publications
Proteomic databases
jPOSTi | P0A725 |
PaxDbi | P0A725 |
PRIDEi | P0A725 |
Interactioni
Protein-protein interaction databases
BioGRIDi | 4261858, 381 interactors 849217, 2 interactors |
DIPi | DIP-48045N |
IntActi | P0A725, 5 interactors |
STRINGi | 511145.b0096 |
Chemistry databases
BindingDBi | P0A725 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P0A725 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
The N-terminus is required for deacetylase activity. The C-terminus contains a signal sequence necessary for FtsH-dependent degradation.1 Publication
Sequence similaritiesi
Belongs to the LpxC family.UniRule annotation
Phylogenomic databases
eggNOGi | COG0774, Bacteria |
HOGENOMi | CLU_046528_1_0_6 |
InParanoidi | P0A725 |
PhylomeDBi | P0A725 |
Family and domain databases
Gene3Di | 3.30.1700.10, 1 hit 3.30.230.20, 1 hit |
HAMAPi | MF_00388, LpxC, 1 hit |
InterProi | View protein in InterPro IPR020568, Ribosomal_S5_D2-typ_fold IPR004463, UDP-acyl_GlcNac_deAcase IPR011334, UDP-acyl_GlcNac_deAcase_C IPR015870, UDP-acyl_N-AcGlcN_deAcase_N |
PANTHERi | PTHR33694, PTHR33694, 1 hit |
Pfami | View protein in Pfam PF03331, LpxC, 1 hit |
SUPFAMi | SSF54211, SSF54211, 2 hits |
TIGRFAMsi | TIGR00325, lpxC, 1 hit |
i Sequence
Sequence statusi: Complete.
P0A725-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MIKQRTLKRI VQATGVGLHT GKKVTLTLRP APANTGVIYR RTDLNPPVDF
60 70 80 90 100
PADAKSVRDT MLCTCLVNEH DVRISTVEHL NAALAGLGID NIVIEVNAPE
110 120 130 140 150
IPIMDGSAAP FVYLLLDAGI DELNCAKKFV RIKETVRVED GDKWAEFKPY
160 170 180 190 200
NGFSLDFTID FNHPAIDSSN QRYAMNFSAD AFMRQISRAR TFGFMRDIEY
210 220 230 240 250
LQSRGLCLGG SFDCAIVVDD YRVLNEDGLR FEDEFVRHKM LDAIGDLFMC
260 270 280 290 300
GHNIIGAFTA YKSGHALNNK LLQAVLAKQE AWEYVTFQDD AELPLAFKAP
SAVLA
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 50 | F → S in ASMB2/3; reduced activity. 1 Publication | 1 | |
Natural varianti | 210 | G → S in ASMB1; reduced activity. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M19211 Genomic DNA Translation: AAA83849.1 X55034 Genomic DNA Translation: CAA38873.1 U00096 Genomic DNA Translation: AAC73207.1 AP009048 Genomic DNA Translation: BAB96664.1 |
PIRi | A28381, BVECEA |
RefSeqi | NP_414638.1, NC_000913.3 WP_000595482.1, NZ_STEB01000010.1 |
Genome annotation databases
EnsemblBacteriai | AAC73207; AAC73207; b0096 BAB96664; BAB96664; BAB96664 |
GeneIDi | 58460764 944816 |
KEGGi | ecj:JW0094 eco:b0096 |
PATRICi | fig|1411691.4.peg.2184 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M19211 Genomic DNA Translation: AAA83849.1 X55034 Genomic DNA Translation: CAA38873.1 U00096 Genomic DNA Translation: AAC73207.1 AP009048 Genomic DNA Translation: BAB96664.1 |
PIRi | A28381, BVECEA |
RefSeqi | NP_414638.1, NC_000913.3 WP_000595482.1, NZ_STEB01000010.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4IS9 | X-ray | 2.13 | A/B | 1-300 | [»] | |
4ISA | X-ray | 1.80 | A | 1-300 | [»] | |
4MDT | X-ray | 2.59 | A/B/C/D | 1-305 | [»] | |
4MQY | X-ray | 2.00 | A | 1-305 | [»] | |
SMRi | P0A725 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4261858, 381 interactors 849217, 2 interactors |
DIPi | DIP-48045N |
IntActi | P0A725, 5 interactors |
STRINGi | 511145.b0096 |
Chemistry databases
BindingDBi | P0A725 |
ChEMBLi | CHEMBL5244 |
SwissLipidsi | SLP:000001888 |
Proteomic databases
jPOSTi | P0A725 |
PaxDbi | P0A725 |
PRIDEi | P0A725 |
Genome annotation databases
EnsemblBacteriai | AAC73207; AAC73207; b0096 BAB96664; BAB96664; BAB96664 |
GeneIDi | 58460764 944816 |
KEGGi | ecj:JW0094 eco:b0096 |
PATRICi | fig|1411691.4.peg.2184 |
Organism-specific databases
EchoBASEi | EB0261 |
Phylogenomic databases
eggNOGi | COG0774, Bacteria |
HOGENOMi | CLU_046528_1_0_6 |
InParanoidi | P0A725 |
PhylomeDBi | P0A725 |
Enzyme and pathway databases
UniPathwayi | UPA00359;UER00478 |
BioCyci | EcoCyc:UDPACYLGLCNACDEACETYL-MONOMER MetaCyc:UDPACYLGLCNACDEACETYL-MONOMER |
Miscellaneous databases
PROi | PR:P0A725 |
Family and domain databases
Gene3Di | 3.30.1700.10, 1 hit 3.30.230.20, 1 hit |
HAMAPi | MF_00388, LpxC, 1 hit |
InterProi | View protein in InterPro IPR020568, Ribosomal_S5_D2-typ_fold IPR004463, UDP-acyl_GlcNac_deAcase IPR011334, UDP-acyl_GlcNac_deAcase_C IPR015870, UDP-acyl_N-AcGlcN_deAcase_N |
PANTHERi | PTHR33694, PTHR33694, 1 hit |
Pfami | View protein in Pfam PF03331, LpxC, 1 hit |
SUPFAMi | SSF54211, SSF54211, 2 hits |
TIGRFAMsi | TIGR00325, lpxC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | LPXC_ECOLI | |
Accessioni | P0A725Primary (citable) accession number: P0A725 Secondary accession number(s): P07652 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1988 |
Last sequence update: | June 7, 2005 | |
Last modified: | April 7, 2021 | |
This is version 119 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families