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Protein

UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase

Gene

lpxD

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

Functioni

Catalyzes the N-acylation of UDP-3-O-(hydroxytetradecanoyl)glucosamine using 3-hydroxytetradecanoyl-ACP as the acyl donor. Is involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. Prefers (3R)-3-hydroxytetradecanoyl-ACP over (3R)-3-hydroxyhexadecanoyl-ACP as the acyl donor in vitro, which is consistent with the structure of E.coli lipid A that contains over 95% (R)-3-hydroxytetradecanoate at the 2 and 2' positions.2 Publications

Catalytic activityi

(3R)-3-hydroxytetradecanoyl-[acyl-carrier-protein] + UDP-3-O-((3R)-hydroxytetradecanoyl)-alpha-D-glucosamine = UDP-2-N,3-O-bis((3R)-3-hydroxytetradecanoyl)-alpha-D-glucosamine + a holo-[acyl-carrier-protein].3 Publications

Enzyme regulationi

Inhibited by divalent cations such as Ca2+ and Mg2+.1 Publication

Kineticsi

kcat is 23 sec(-1).

  1. KM=2.5 µM for UDP-3-O-((3R)-hydroxytetradecanoyl)-alpha-D-glucosamine1 Publication
  2. KM=3.2 µM for (3R)-3-hydroxytetradecanoyl-ACP1 Publication

    Pathwayi: lipid IV(A) biosynthesis

    This protein is involved in step 3 of the subpathway that synthesizes lipid IV(A) from (3R)-3-hydroxytetradecanoyl-[acyl-carrier-protein] and UDP-N-acetyl-alpha-D-glucosamine.
    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)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei239 – 2391Proton acceptor1 Publication
    Sitei290 – 2901Involved in determining the hydroxyacyl-ACP selectivity

    GO - Molecular functioni

    GO - Biological processi

    • lipid A biosynthetic process Source: EcoliWiki
    • response to antibiotic Source: UniProtKB-KW
    Complete GO annotation...

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Antibiotic resistance, Lipid A biosynthesis, Lipid biosynthesis, Lipid metabolism

    Enzyme and pathway databases

    BioCyciEcoCyc:UDPHYDROXYMYRGLUCOSAMNACETYLTRANS-MONO.
    ECOL316407:JW0174-MONOMER.
    MetaCyc:UDPHYDROXYMYRGLUCOSAMNACETYLTRANS-MONO.
    BRENDAi2.3.1.191. 2026.
    UniPathwayiUPA00359; UER00479.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase (EC:2.3.1.191)
    Short name:
    UDP-3-O-(3-OHC14)-GlcN N-acyltransferase
    Alternative name(s):
    Protein FirA
    Rifampicin resistance protein
    UDP-3-O-(3-hydroxytetradecanoyl)glucosamine N-acyltransferase
    Gene namesi
    Name:lpxD
    Synonyms:firA, omsA
    Ordered Locus Names:b0179, JW0174
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10316. lpxD.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: EcoCyc
    • cytosol Source: EcoCyc
    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi41 – 411F → A: 30-fold decrease in affinity for UDP-3-O-((3R)-hydroxytetradecanoyl)-GlcN and 5-fold decrease in catalytic activity. 1 Publication
    Mutagenesisi165 – 1651Q → R in firA200; confers temperature sensitivity and reverses the rifampicin resistance of rpoB mutants. 1 Publication
    Mutagenesisi172 – 1721I → F in firA201; confers temperature sensitivity.
    Mutagenesisi228 – 2281G → D in firA200 and firA201; confers temperature sensitivity. 1 Publication
    Mutagenesisi239 – 2391H → A: 1000-fold reduction in catalytic activity with very little effect on substrate affinity. 1 Publication
    Mutagenesisi252 – 2521G → S in firA200 and firA201; confers temperature sensitivity. 1 Publication
    Mutagenesisi271 – 2711S → N in omsA; confers temperature sensitivity. 1 Publication
    Mutagenesisi276 – 2761H → A: 30-fold reduction in catalytic activity. 1 Publication
    Mutagenesisi290 – 2901M → A: Change in the acyl donor selectivity, showing a preference for 3-hydroxypalmitoyl-ACP over 3-hydroxytetradecanoyl-ACP as substrate. Produces a lipid A with longer acyl chains. 1 Publication
    Mutagenesisi292 – 2921M → A: No change in the acyl donor selectivity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methionineiRemoved1 Publication
    Chaini2 – 341340UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferasePRO_0000059669Add
    BLAST

    Proteomic databases

    EPDiP21645.
    PaxDbiP21645.
    PRIDEiP21645.

    Interactioni

    Subunit structurei

    Homotrimer.2 Publications

    GO - Molecular functioni

    • identical protein binding Source: EcoCyc

    Protein-protein interaction databases

    BioGridi4259589. 431 interactions.
    DIPiDIP-10124N.
    IntActiP21645. 55 interactions.
    MINTiMINT-1218299.
    STRINGi511145.b0179.

    Structurei

    Secondary structure

    1
    341
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi6 – 127Combined sources
    Beta strandi16 – 194Combined sources
    Turni31 – 333Combined sources
    Beta strandi38 – 414Combined sources
    Helixi45 – 539Combined sources
    Beta strandi57 – 615Combined sources
    Turni63 – 653Combined sources
    Helixi66 – 683Combined sources
    Beta strandi71 – 755Combined sources
    Helixi79 – 8911Combined sources
    Beta strandi177 – 1804Combined sources
    Beta strandi185 – 1884Combined sources
    Beta strandi191 – 1944Combined sources
    Beta strandi201 – 2033Combined sources
    Beta strandi214 – 2163Combined sources
    Beta strandi219 – 2213Combined sources
    Beta strandi223 – 2253Combined sources
    Beta strandi259 – 2613Combined sources
    Beta strandi275 – 2795Combined sources
    Beta strandi281 – 2855Combined sources
    Beta strandi299 – 3024Combined sources
    Helixi310 – 32112Combined sources
    Helixi323 – 33715Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3EH0X-ray2.60A/B/C1-341[»]
    4IHFX-ray2.10A/B/C/D/E/F3-341[»]
    4IHGX-ray2.89A/B/C/D/E/F3-341[»]
    4IHHX-ray2.13A/B/C/D/E/F3-341[»]
    ProteinModelPortaliP21645.
    SMRiP21645. Positions 3-339.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP21645.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiENOG4105D7M. Bacteria.
    COG1044. LUCA.
    HOGENOMiHOG000294339.
    InParanoidiP21645.
    KOiK02536.
    OMAiWANVTLY.
    OrthoDBiEOG6JB11D.
    PhylomeDBiP21645.

    Family and domain databases

    HAMAPiMF_00523. LpxD.
    InterProiIPR001451. Hexapep.
    IPR018357. Hexapep_transf_CS.
    IPR007691. LpxD.
    IPR011004. Trimer_LpxA-like.
    IPR020573. UDP_GlcNAc_AcTrfase_non-rep.
    [Graphical view]
    PfamiPF00132. Hexapep. 3 hits.
    PF14602. Hexapep_2. 1 hit.
    PF04613. LpxD. 1 hit.
    [Graphical view]
    SUPFAMiSSF51161. SSF51161. 1 hit.
    TIGRFAMsiTIGR01853. lipid_A_lpxD. 1 hit.
    PROSITEiPS00101. HEXAPEP_TRANSFERASES. 4 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P21645-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPSIRLADLA QQLDAELHGD GDIVITGVAS MQSAQTGHIT FMVNPKYREH
    60 70 80 90 100
    LGLCQASAVV MTQDDLPFAK SAALVVKNPY LTYARMAQIL DTTPQPAQNI
    110 120 130 140 150
    APSAVIDATA KLGNNVSIGA NAVIESGVEL GDNVIIGAGC FVGKNSKIGA
    160 170 180 190 200
    GSRLWANVTI YHEIQIGQNC LIQSGTVVGA DGFGYANDRG NWVKIPQIGR
    210 220 230 240 250
    VIIGDRVEIG ACTTIDRGAL DDTIIGNGVI IDNQCQIAHN VVIGDNTAVA
    260 270 280 290 300
    GGVIMAGSLK IGRYCMIGGA SVINGHMEIC DKVTVTGMGM VMRPITEPGV
    310 320 330 340
    YSSGIPLQPN KVWRKTAALV MNIDDMSKRL KSLERKVNQQ D
    Length:341
    Mass (Da):36,038
    Last modified:January 23, 2007 - v2
    Checksum:iB0ADFED5B17C649D
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X54797 Genomic DNA. Translation: CAA38568.1.
    U70214 Genomic DNA. Translation: AAB08608.1.
    U00096 Genomic DNA. Translation: AAC73290.1.
    AP009048 Genomic DNA. Translation: BAA77854.1.
    PIRiS13729.
    RefSeqiNP_414721.1. NC_000913.3.
    WP_001139279.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC73290; AAC73290; b0179.
    BAA77854; BAA77854; BAA77854.
    GeneIDi944882.
    KEGGiecj:JW0174.
    eco:b0179.
    PATRICi32115469. VBIEscCol129921_0186.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X54797 Genomic DNA. Translation: CAA38568.1.
    U70214 Genomic DNA. Translation: AAB08608.1.
    U00096 Genomic DNA. Translation: AAC73290.1.
    AP009048 Genomic DNA. Translation: BAA77854.1.
    PIRiS13729.
    RefSeqiNP_414721.1. NC_000913.3.
    WP_001139279.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3EH0X-ray2.60A/B/C1-341[»]
    4IHFX-ray2.10A/B/C/D/E/F3-341[»]
    4IHGX-ray2.89A/B/C/D/E/F3-341[»]
    4IHHX-ray2.13A/B/C/D/E/F3-341[»]
    ProteinModelPortaliP21645.
    SMRiP21645. Positions 3-339.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4259589. 431 interactions.
    DIPiDIP-10124N.
    IntActiP21645. 55 interactions.
    MINTiMINT-1218299.
    STRINGi511145.b0179.

    Proteomic databases

    EPDiP21645.
    PaxDbiP21645.
    PRIDEiP21645.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC73290; AAC73290; b0179.
    BAA77854; BAA77854; BAA77854.
    GeneIDi944882.
    KEGGiecj:JW0174.
    eco:b0179.
    PATRICi32115469. VBIEscCol129921_0186.

    Organism-specific databases

    EchoBASEiEB0312.
    EcoGeneiEG10316. lpxD.

    Phylogenomic databases

    eggNOGiENOG4105D7M. Bacteria.
    COG1044. LUCA.
    HOGENOMiHOG000294339.
    InParanoidiP21645.
    KOiK02536.
    OMAiWANVTLY.
    OrthoDBiEOG6JB11D.
    PhylomeDBiP21645.

    Enzyme and pathway databases

    UniPathwayiUPA00359; UER00479.
    BioCyciEcoCyc:UDPHYDROXYMYRGLUCOSAMNACETYLTRANS-MONO.
    ECOL316407:JW0174-MONOMER.
    MetaCyc:UDPHYDROXYMYRGLUCOSAMNACETYLTRANS-MONO.
    BRENDAi2.3.1.191. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP21645.
    PROiP21645.

    Family and domain databases

    HAMAPiMF_00523. LpxD.
    InterProiIPR001451. Hexapep.
    IPR018357. Hexapep_transf_CS.
    IPR007691. LpxD.
    IPR011004. Trimer_LpxA-like.
    IPR020573. UDP_GlcNAc_AcTrfase_non-rep.
    [Graphical view]
    PfamiPF00132. Hexapep. 3 hits.
    PF14602. Hexapep_2. 1 hit.
    PF04613. LpxD. 1 hit.
    [Graphical view]
    SUPFAMiSSF51161. SSF51161. 1 hit.
    TIGRFAMsiTIGR01853. lipid_A_lpxD. 1 hit.
    PROSITEiPS00101. HEXAPEP_TRANSFERASES. 4 hits.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Cloning and nucleotide sequence of the firA gene and the firA200(Ts) allele from Escherichia coli."
      Dicker I.B., Seetharam S.R.
      J. Bacteriol. 173:334-344(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-15, MUTAGENESIS OF GLN-165; GLY-228 AND GLY-252.
      Strain: K12 / MG1655 / ATCC 47076.
    2. "Systematic sequencing of the Escherichia coli genome: analysis of the 4.0 - 6.0 min (189,987 - 281,416bp) region."
      Takemoto K., Mori H., Murayama N., Kataoka K., Yano M., Itoh T., Yamamoto Y., Inokuchi H., Miki T., Hatada E., Fukuda R., Ichihara S., Mizuno T., Makino K., Nakata A., Yura T., Sampei G., Mizobuchi K.
      Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    3. "Sequence of minutes 4-25 of Escherichia coli."
      Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.
      Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    5. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    6. "What is known about the structure and function of the Escherichia coli protein FirA?"
      Dicker I.B., Seetharam S.R.
      Mol. Microbiol. 6:817-823(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    7. "Mutants carrying conditionally lethal mutations in outer membrane genes omsA and firA (ssc) are phenotypically similar, and omsA is allelic to firA."
      Vuorio R., Vaara M.
      J. Bacteriol. 174:7090-7097(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF SER-271.
    8. "Defective biosynthesis of the lipid A component of temperature-sensitive firA (omsA) mutant of Escherichia coli."
      Helander I.M., Lindner B., Seydel U., Vaara M.
      Eur. J. Biochem. 212:363-369(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION.
    9. "The firA gene of Escherichia coli encodes UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase. The third step of endotoxin biosynthesis."
      Kelly T.M., Stachula S.A., Raetz C.R.H., Anderson M.S.
      J. Biol. Chem. 268:19866-19874(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION.
    10. "Steady-state kinetics and mechanism of LpxD, the N-acyltransferase of lipid A biosynthesis."
      Bartling C.M., Raetz C.R.
      Biochemistry 47:5290-5302(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, KINETIC PARAMETERS, SUBUNIT, REACTION MECHANISM, ACTIVE SITE, MUTAGENESIS OF PHE-41; HIS-239 AND HIS-276.
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    11. "Crystal structure and acyl chain selectivity of Escherichia coli LpxD, the N-acyltransferase of lipid A biosynthesis."
      Bartling C.M., Raetz C.R.
      Biochemistry 48:8672-8683(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, SUBUNIT, CATALYTIC MECHANISM, MUTAGENESIS OF MET-290 AND MET-292.
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.

    Entry informationi

    Entry nameiLPXD_ECOLI
    AccessioniPrimary (citable) accession number: P21645
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 1991
    Last sequence update: January 23, 2007
    Last modified: June 8, 2016
    This is version 140 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Caution

    Was originally thought to be involved in transcription.Curated

    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.