LPXH_ECOLI
ID LPXH_ECOLI Reviewed; 240 AA.
AC P43341; P77440; Q2MBQ5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=UDP-2,3-diacylglucosamine hydrolase {ECO:0000255|HAMAP-Rule:MF_00575, ECO:0000303|PubMed:12000770};
DE EC=3.6.1.54 {ECO:0000255|HAMAP-Rule:MF_00575, ECO:0000269|PubMed:12000770, ECO:0000269|PubMed:12000771};
DE AltName: Full=UDP-2,3-diacylglucosamine diphosphatase {ECO:0000255|HAMAP-Rule:MF_00575};
DE AltName: Full=UDP-2,3-diacylglucosamine pyrophosphatase {ECO:0000303|PubMed:12000771};
GN Name=lpxH {ECO:0000255|HAMAP-Rule:MF_00575, ECO:0000303|PubMed:12000770};
GN Synonyms=ybbF; OrderedLocusNames=b0524, JW0513;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION,
RP PATHWAY, AND SUBCELLULAR LOCATION.
RX PubMed=12000770; DOI=10.1074/jbc.m204067200;
RA Babinski K.J., Ribeiro A.A., Raetz C.R.H.;
RT "The Escherichia coli gene encoding the UDP-2,3-diacylglucosamine
RT pyrophosphatase of lipid A biosynthesis.";
RL J. Biol. Chem. 277:25937-25946(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 151-240.
RX PubMed=2644189; DOI=10.1128/jb.171.1.198-204.1989;
RA Watanabe W., Sampei G., Aiba A., Mizobuchi K.;
RT "Identification and sequence analysis of Escherichia coli purE and purK
RT genes encoding 5'-phosphoribosyl-5-amino-4-imidazole carboxylase for de
RT novo purine biosynthesis.";
RL J. Bacteriol. 171:198-204(1989).
RN [6]
RP IDENTIFICATION.
RX PubMed=7567469; DOI=10.1093/nar/23.17.3554;
RA Borodovsky M., McIninch J., Koonin E.V., Rudd K.E., Medigue C., Danchin A.;
RT "Detection of new genes in a bacterial genome using Markov models for three
RT gene classes.";
RL Nucleic Acids Res. 23:3554-3562(1995).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=12000771; DOI=10.1074/jbc.m204068200;
RA Babinski K.J., Kanjilal S.J., Raetz C.R.H.;
RT "Accumulation of the lipid A precursor UDP-2,3-diacylglucosamine in an
RT Escherichia coli mutant lacking the lpxH gene.";
RL J. Biol. Chem. 277:25947-25956(2002).
RN [8]
RP ACTIVITY REGULATION.
RX PubMed=25733621; DOI=10.1128/jb.02552-14;
RA Nayar A.S., Dougherty T.J., Ferguson K.E., Granger B.A., McWilliams L.,
RA Stacey C., Leach L.J., Narita S., Tokuda H., Miller A.A., Brown D.G.,
RA McLeod S.M.;
RT "Novel antibacterial targets and compounds revealed by a high-throughput
RT cell wall reporter assay.";
RL J. Bacteriol. 197:1726-1734(2015).
CC -!- FUNCTION: Hydrolyzes the pyrophosphate bond of UDP-2,3-
CC diacylglucosamine to yield 2,3-diacylglucosamine 1-phosphate (lipid X)
CC and UMP by catalyzing the attack of water at the alpha-P atom
CC (PubMed:12000770). Involved in the biosynthesis of lipid A, a
CC phosphorylated glycolipid that anchors the lipopolysaccharide to the
CC outer membrane of the cell (PubMed:12000770, PubMed:12000771). Is
CC essential for E.coli growth (PubMed:12000771). Does not cleave the
CC unacylated UDP-GlcNAc, the mono-acylated UDP-3-O-(R)-3-
CC hydroxymyristoyl-GlcNAc, and CDP-diacylglycerol (PubMed:12000770).
CC {ECO:0000269|PubMed:12000770, ECO:0000269|PubMed:12000771}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-alpha-D-
CC glucosamine = 2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-alpha-D-
CC glucosaminyl 1-phosphate + 2 H(+) + UMP; Xref=Rhea:RHEA:25213,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57865,
CC ChEBI:CHEBI:57957, ChEBI:CHEBI:78847; EC=3.6.1.54;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00575,
CC ECO:0000269|PubMed:12000770, ECO:0000269|PubMed:12000771};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00575,
CC ECO:0000305|PubMed:12000770};
CC Note=Binds 2 Mn(2+) ions per subunit in a binuclear metal center.
CC {ECO:0000255|HAMAP-Rule:MF_00575};
CC -!- ACTIVITY REGULATION: Inhibited by a sulfonyl piperazine compound that
CC shows antibacterial activity against E.coli; LpxH is the cellular
CC target of this compound (PubMed:25733621). Inhibited by 0.01% (or more)
CC Triton X-100 in vitro (PubMed:12000770). {ECO:0000269|PubMed:12000770,
CC ECO:0000269|PubMed:25733621}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=61.7 uM for UDP-2-N,3-O-bis((3R)-3-hydroxytetradecanoyl)-alpha-D-
CC glucosamine {ECO:0000269|PubMed:12000770};
CC Vmax=17.2 umol/min/mg enzyme {ECO:0000269|PubMed:12000770};
CC Note=Assays with partially purified enzyme.
CC {ECO:0000305|PubMed:12000770};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:12000770};
CC -!- PATHWAY: Glycolipid biosynthesis; lipid IV(A) biosynthesis; lipid IV(A)
CC from (3R)-3-hydroxytetradecanoyl-[acyl-carrier-protein] and UDP-N-
CC acetyl-alpha-D-glucosamine: step 4/6. {ECO:0000255|HAMAP-Rule:MF_00575,
CC ECO:0000305|PubMed:12000770, ECO:0000305|PubMed:12000771}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000305|PubMed:12000770}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12000770}; Cytoplasmic side
CC {ECO:0000305|PubMed:12000770}. Cytoplasm {ECO:0000269|PubMed:12000770}.
CC -!- DISRUPTION PHENOTYPE: An insertion mutation defective in lpxH is not
CC viable and accumulates UDP-2,3-diacylglucosamine.
CC {ECO:0000269|PubMed:12000771}.
CC -!- SIMILARITY: Belongs to the LpxH family. {ECO:0000255|HAMAP-
CC Rule:MF_00575}.
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DR EMBL; AF311865; AAG47820.1; -; Genomic_DNA.
DR EMBL; U82664; AAB40277.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73626.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76301.1; -; Genomic_DNA.
DR EMBL; M19657; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; C64784; C64784.
DR RefSeq; NP_415057.1; NC_000913.3.
DR RefSeq; WP_000212247.1; NZ_SSZK01000024.1.
DR PDB; 5WLY; X-ray; 2.00 A; A=1-240.
DR PDBsum; 5WLY; -.
DR AlphaFoldDB; P43341; -.
DR SMR; P43341; -.
DR BioGRID; 4262817; 215.
DR DIP; DIP-10125N; -.
DR IntAct; P43341; 20.
DR STRING; 511145.b0524; -.
DR PaxDb; P43341; -.
DR PRIDE; P43341; -.
DR EnsemblBacteria; AAC73626; AAC73626; b0524.
DR EnsemblBacteria; BAE76301; BAE76301; BAE76301.
DR GeneID; 949053; -.
DR KEGG; ecj:JW0513; -.
DR KEGG; eco:b0524; -.
DR PATRIC; fig|1411691.4.peg.1754; -.
DR EchoBASE; EB2532; -.
DR eggNOG; COG2908; Bacteria.
DR HOGENOM; CLU_074586_0_0_6; -.
DR InParanoid; P43341; -.
DR OMA; FDFWFEY; -.
DR PhylomeDB; P43341; -.
DR BioCyc; EcoCyc:EG12666-MON; -.
DR BioCyc; MetaCyc:EG12666-MON; -.
DR BRENDA; 3.6.1.54; 2026.
DR UniPathway; UPA00359; UER00480.
DR PRO; PR:P43341; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:EcoCyc.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IBA:GO_Central.
DR GO; GO:0030145; F:manganese ion binding; IDA:EcoCyc.
DR GO; GO:0008758; F:UDP-2,3-diacylglucosamine hydrolase activity; IDA:UniProtKB.
DR GO; GO:0009245; P:lipid A biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.60.21.10; -; 1.
DR HAMAP; MF_00575; LpxH; 1.
DR InterPro; IPR024654; Calcineurin-like_PHP_lpxH.
DR InterPro; IPR043461; LpxH-like.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR010138; UDP-diacylglucosamine_Hdrlase.
DR PANTHER; PTHR34990; PTHR34990; 1.
DR PANTHER; PTHR34990:SF1; PTHR34990:SF1; 1.
DR Pfam; PF12850; Metallophos_2; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR TIGRFAMs; TIGR01854; lipid_A_lpxH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane; Cytoplasm; Hydrolase;
KW Lipid A biosynthesis; Lipid biosynthesis; Lipid metabolism; Manganese;
KW Membrane; Metal-binding; Reference proteome.
FT CHAIN 1..240
FT /note="UDP-2,3-diacylglucosamine hydrolase"
FT /id="PRO_0000214108"
FT BINDING 8
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 10
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 41
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 41
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 79..80
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 79
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 114
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 122
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 160
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 164
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 167
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 195
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 195
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT BINDING 197
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00575"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:5WLY"
FT HELIX 16..27
FT /evidence="ECO:0007829|PDB:5WLY"
FT HELIX 29..32
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:5WLY"
FT HELIX 54..68
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:5WLY"
FT HELIX 86..92
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:5WLY"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:5WLY"
FT HELIX 135..141
FT /evidence="ECO:0007829|PDB:5WLY"
FT HELIX 146..160
FT /evidence="ECO:0007829|PDB:5WLY"
FT HELIX 176..185
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 200..206
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 219..228
FT /evidence="ECO:0007829|PDB:5WLY"
FT STRAND 233..238
FT /evidence="ECO:0007829|PDB:5WLY"
SQ SEQUENCE 240 AA; 26894 MW; 5004A2E471B7A7E9 CRC64;
MATLFIADLH LCVEEPAITA GFLRFLAGEA RKADALYILG DLFEAWIGDD DPNPLHRKMA
AAIKAVSDSG VPCYFIHGNR DFLLGKRFAR ESGMTLLPEE KVLELYGRRV LIMHGDTLCT
DDAGYQAFRA KVHKPWLQTL FLALPLFVRK RIAARMRANS KEANSSKSLA IMDVNQNAVV
SAMEKHQVQW LIHGHTHRPA VHELIANQQP AFRVVLGAWH TEGSMVKVTA DDVELIHFPF
