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Protein

UDP-3-O-acyl-N-acetylglucosamine deacetylase

Gene

lpxC

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Catalytic activityi

UDP-3-O-((3R)-3-hydroxytetradecanoyl)-N-acetyl-alpha-D-glucosamine + H2O = UDP-3-O-((3R)-3-hydroxytetradecanoyl)-alpha-D-glucosamine + acetate.UniRule 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

Enzyme 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

Manual assertion based on experiment ini

  1. KM=2.1 µM for UDP-3-O-myristoyl-N-acetylglucosamine (at 30 degrees Celsius)1 Publication
  2. KM=0.6 µM for UDP-3-O-myristoyl-N-acetylglucosamine (at 1 degree Celsius)1 Publication

    Pathwayi: lipid IV(A) biosynthesis

    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 Publication
    Proteins known to be involved in the 6 steps of the subpathway in this organism are:
    1. Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase (lpxA)
    2. UDP-3-O-acyl-N-acetylglucosamine deacetylase (lpxC)
    3. UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase (lpxD)
    4. UDP-2,3-diacylglucosamine hydrolase (lpxH)
    5. Lipid-A-disaccharide synthase (lpxB)
    6. Tetraacyldisaccharide 4'-kinase (lpxK)
    This subpathway is part of the pathway lipid IV(A) biosynthesis, which is itself part of Glycolipid biosynthesis.
    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 keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi79Zinc; via tele nitrogenUniRule annotation2 Publications1
    Metal bindingi238Zinc; via tele nitrogenUniRule annotation2 Publications1
    Metal bindingi242ZincUniRule annotation2 Publications1
    Active sitei265Proton donorUniRule annotation2 Publications1

    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
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Lipid A biosynthesis, Lipid biosynthesis, Lipid metabolism

    Keywords - Ligandi

    Iron, Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciEcoCyc:UDPACYLGLCNACDEACETYL-MONOMER.
    ECOL316407:JW0094-MONOMER.
    MetaCyc:UDPACYLGLCNACDEACETYL-MONOMER.
    UniPathwayiUPA00359; UER00478.

    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
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10265. lpxC.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: EcoCyc
    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi19H → A: 1400-fold decrease in activity. 1 Publication1
    Mutagenesisi19H → Q: 90-fold decrease in activity. 1 Publication1
    Mutagenesisi19H → Y: 200-fold decrease in activity. 1 Publication1
    Mutagenesisi63C → A: Reduces level of inhibition by metal ions. 1 Publication1
    Mutagenesisi78E → A: 700-fold decrease in activity. 1 Publication1
    Mutagenesisi78E → Q: 3000-fold decrease in activity. 1 Publication1
    Mutagenesisi79H → A: 2300-fold decrease in activity. 1 Publication1
    Mutagenesisi79H → Q: 1200-fold decrease in activity. 1 Publication1
    Mutagenesisi238H → A: 1100-fold decrease in activity. 1 Publication1
    Mutagenesisi242D → A: 10-fold decrease in activity. 1 Publication1
    Mutagenesisi242D → Q: 2300-fold decrease in activity. 1 Publication1
    Mutagenesisi246D → A: 1800-fold decrease in activity. 1 Publication1
    Mutagenesisi265H → A: 3800-fold decrease in activity. 1 Publication1
    Mutagenesisi265H → Q: 5600-fold decrease in activity. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL5244.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001919291 – 305UDP-3-O-acyl-N-acetylglucosamine deacetylaseAdd BLAST305

    Post-translational modificationi

    Degraded by FtsH.4 Publications

    Proteomic databases

    PaxDbiP0A725.
    PRIDEiP0A725.

    Interactioni

    Protein-protein interaction databases

    BioGridi4261858. 357 interactors.
    DIPiDIP-48045N.
    IntActiP0A725. 5 interactors.
    MINTiMINT-1309717.
    STRINGi511145.b0096.

    Chemistry databases

    BindingDBiP0A725.

    Structurei

    Secondary structure

    1305
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi3 – 9Combined sources7
    Beta strandi11 – 16Combined sources6
    Turni18 – 20Combined sources3
    Beta strandi22 – 29Combined sources8
    Beta strandi37 – 41Combined sources5
    Beta strandi43 – 46Combined sources4
    Beta strandi48 – 51Combined sources4
    Helixi54 – 56Combined sources3
    Beta strandi61 – 63Combined sources3
    Beta strandi65 – 67Combined sources3
    Beta strandi73 – 75Combined sources3
    Helixi78 – 87Combined sources10
    Beta strandi91 – 100Combined sources10
    Beta strandi106 – 108Combined sources3
    Helixi109 – 118Combined sources10
    Beta strandi120 – 126Combined sources7
    Beta strandi129 – 132Combined sources4
    Beta strandi136 – 140Combined sources5
    Beta strandi143 – 148Combined sources6
    Beta strandi151 – 158Combined sources8
    Helixi168 – 170Combined sources3
    Beta strandi171 – 176Combined sources6
    Helixi179 – 185Combined sources7
    Turni186 – 188Combined sources3
    Beta strandi192 – 194Combined sources3
    Helixi195 – 202Combined sources8
    Turni203 – 205Combined sources3
    Beta strandi214 – 218Combined sources5
    Beta strandi220 – 223Combined sources4
    Helixi234 – 247Combined sources14
    Helixi248 – 250Combined sources3
    Beta strandi254 – 262Combined sources9
    Helixi265 – 277Combined sources13
    Helixi279 – 281Combined sources3
    Beta strandi282 – 285Combined sources4
    Helixi290 – 292Combined sources3
    Helixi295 – 297Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4IS9X-ray2.13A/B1-300[»]
    4ISAX-ray1.80A1-300[»]
    4MDTX-ray2.59A/B/C/D1-305[»]
    4MQYX-ray2.00A1-305[»]
    ProteinModelPortaliP0A725.
    SMRiP0A725.
    ModBaseiSearch...
    MobiDBiSearch...

    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

    eggNOGiENOG4105C7C. Bacteria.
    COG0774. LUCA.
    HOGENOMiHOG000256663.
    InParanoidiP0A725.
    KOiK02535.
    OMAiNSMLVKA.
    PhylomeDBiP0A725.

    Family and domain databases

    Gene3Di3.30.1700.10. 1 hit.
    3.30.230.20. 1 hit.
    HAMAPiMF_00388. LpxC. 1 hit.
    InterProiIPR020568. Ribosomal_S5_D2-typ_fold.
    IPR004463. UDP-acyl_GlcNac_deAcase.
    IPR011334. UDP-acyl_GlcNac_deAcase_C.
    IPR015870. UDP-acyl_N-AcGlcN_deAcase_N.
    [Graphical view]
    PfamiPF03331. LpxC. 1 hit.
    [Graphical view]
    SUPFAMiSSF54211. SSF54211. 2 hits.
    TIGRFAMsiTIGR00325. lpxC. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P0A725-1 [UniParc]FASTAAdd to basket

    « Hide

            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
    Length:305
    Mass (Da):33,956
    Last modified:June 7, 2005 - v1
    Checksum:iCA439A00813463AB
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural varianti50F → S in ASMB2/3; reduced activity. 1 Publication1
    Natural varianti210G → S in ASMB1; reduced activity. 1 Publication1

    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.
    PIRiA28381. BVECEA.
    RefSeqiNP_414638.1. NC_000913.3.
    WP_000595482.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC73207; AAC73207; b0096.
    BAB96664; BAB96664; BAB96664.
    GeneIDi944816.
    KEGGiecj:JW0094.
    eco:b0096.
    PATRICi32115297. VBIEscCol129921_0100.

    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.
    PIRiA28381. BVECEA.
    RefSeqiNP_414638.1. NC_000913.3.
    WP_000595482.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4IS9X-ray2.13A/B1-300[»]
    4ISAX-ray1.80A1-300[»]
    4MDTX-ray2.59A/B/C/D1-305[»]
    4MQYX-ray2.00A1-305[»]
    ProteinModelPortaliP0A725.
    SMRiP0A725.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4261858. 357 interactors.
    DIPiDIP-48045N.
    IntActiP0A725. 5 interactors.
    MINTiMINT-1309717.
    STRINGi511145.b0096.

    Chemistry databases

    BindingDBiP0A725.
    ChEMBLiCHEMBL5244.

    Proteomic databases

    PaxDbiP0A725.
    PRIDEiP0A725.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC73207; AAC73207; b0096.
    BAB96664; BAB96664; BAB96664.
    GeneIDi944816.
    KEGGiecj:JW0094.
    eco:b0096.
    PATRICi32115297. VBIEscCol129921_0100.

    Organism-specific databases

    EchoBASEiEB0261.
    EcoGeneiEG10265. lpxC.

    Phylogenomic databases

    eggNOGiENOG4105C7C. Bacteria.
    COG0774. LUCA.
    HOGENOMiHOG000256663.
    InParanoidiP0A725.
    KOiK02535.
    OMAiNSMLVKA.
    PhylomeDBiP0A725.

    Enzyme and pathway databases

    UniPathwayiUPA00359; UER00478.
    BioCyciEcoCyc:UDPACYLGLCNACDEACETYL-MONOMER.
    ECOL316407:JW0094-MONOMER.
    MetaCyc:UDPACYLGLCNACDEACETYL-MONOMER.

    Miscellaneous databases

    PROiP0A725.

    Family and domain databases

    Gene3Di3.30.1700.10. 1 hit.
    3.30.230.20. 1 hit.
    HAMAPiMF_00388. LpxC. 1 hit.
    InterProiIPR020568. Ribosomal_S5_D2-typ_fold.
    IPR004463. UDP-acyl_GlcNac_deAcase.
    IPR011334. UDP-acyl_GlcNac_deAcase_C.
    IPR015870. UDP-acyl_N-AcGlcN_deAcase_N.
    [Graphical view]
    PfamiPF03331. LpxC. 1 hit.
    [Graphical view]
    SUPFAMiSSF54211. SSF54211. 2 hits.
    TIGRFAMsiTIGR00325. lpxC. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiLPXC_ECOLI
    AccessioniPrimary (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: November 2, 2016
    This is version 94 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    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

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.