LPXH_PSEAE
ID LPXH_PSEAE Reviewed; 240 AA.
AC Q9I2V0;
DT 02-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=UDP-2,3-diacylglucosamine hydrolase {ECO:0000255|HAMAP-Rule:MF_00575, ECO:0000303|PubMed:12000771};
DE EC=3.6.1.54 {ECO:0000255|HAMAP-Rule:MF_00575, ECO:0000269|PubMed:12000771};
DE AltName: Full=UDP-2,3-diacylglucosamine diphosphatase {ECO:0000255|HAMAP-Rule:MF_00575};
GN Name=lpxH {ECO:0000255|HAMAP-Rule:MF_00575, ECO:0000303|PubMed:12000771};
GN OrderedLocusNames=PA1792;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
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 [3]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF WILD-TYPE AND MUTANT ASN-10 IN
RP COMPLEXES WITH MANGANESE AND ITS PRODUCT LIPID X, COFACTOR, DOMAIN,
RP MUTAGENESIS OF HIS-10, AND REACTION MECHANISM.
RX PubMed=27609419; DOI=10.1038/srep32822;
RA Okada C., Wakabayashi H., Kobayashi M., Shinoda A., Tanaka I., Yao M.;
RT "Crystal structures of the UDP-diacylglucosamine pyrophosphohydrase LpxH
RT from Pseudomonas aeruginosa.";
RL Sci. Rep. 6:32822-32822(2016).
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. Involved
CC in the biosynthesis of lipid A, a phosphorylated glycolipid that
CC anchors the lipopolysaccharide to the outer membrane of the cell. Can
CC functionally complement lpxH deficiency in E.coli. {ECO:0000255|HAMAP-
CC Rule:MF_00575, 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:12000771};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00575,
CC ECO:0000305|PubMed:27609419};
CC Note=Binds 2 Mn(2+) ions per subunit in a binuclear metal center.
CC {ECO:0000255|HAMAP-Rule:MF_00575, ECO:0000269|PubMed:27609419};
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:12000771}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_00575}; Peripheral membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_00575}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_00575}.
CC -!- DOMAIN: Consists of two domains: a catalytic domain homologous to
CC metallophosphoesterases (MPEs) and a helical insertion domain (HI
CC domain) inserted in the middle of the catalytic domain.
CC {ECO:0000269|PubMed:27609419}.
CC -!- SIMILARITY: Belongs to the LpxH family. {ECO:0000255|HAMAP-
CC Rule:MF_00575}.
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DR EMBL; AE004091; AAG05181.1; -; Genomic_DNA.
DR PIR; D83421; D83421.
DR RefSeq; NP_250483.1; NC_002516.2.
DR RefSeq; WP_003113585.1; NZ_QZGE01000003.1.
DR PDB; 5B49; X-ray; 1.65 A; A/B=1-240.
DR PDB; 5B4A; X-ray; 1.72 A; A/B=1-240.
DR PDB; 5B4B; X-ray; 1.60 A; A/B=1-240.
DR PDB; 5B4C; X-ray; 1.96 A; A/B=1-240.
DR PDB; 5B4D; X-ray; 1.75 A; A/B=1-240.
DR PDBsum; 5B49; -.
DR PDBsum; 5B4A; -.
DR PDBsum; 5B4B; -.
DR PDBsum; 5B4C; -.
DR PDBsum; 5B4D; -.
DR AlphaFoldDB; Q9I2V0; -.
DR SMR; Q9I2V0; -.
DR STRING; 287.DR97_94; -.
DR PaxDb; Q9I2V0; -.
DR PRIDE; Q9I2V0; -.
DR DNASU; 878790; -.
DR EnsemblBacteria; AAG05181; AAG05181; PA1792.
DR GeneID; 878790; -.
DR KEGG; pae:PA1792; -.
DR PATRIC; fig|208964.12.peg.1859; -.
DR PseudoCAP; PA1792; -.
DR HOGENOM; CLU_074586_0_0_6; -.
DR InParanoid; Q9I2V0; -.
DR OMA; FDFWFEY; -.
DR PhylomeDB; Q9I2V0; -.
DR BioCyc; PAER208964:G1FZ6-1824-MON; -.
DR BRENDA; 3.6.1.54; 5087.
DR UniPathway; UPA00359; UER00480.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IBA:GO_Central.
DR GO; GO:0051861; F:glycolipid binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0008758; F:UDP-2,3-diacylglucosamine hydrolase activity; IDA:UniProtKB.
DR GO; GO:0009245; P:lipid A biosynthetic process; IGI:UniProtKB.
DR Gene3D; 3.60.21.10; -; 1.
DR HAMAP; MF_00575; LpxH; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
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; PF00149; Metallophos; 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; 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_0000214117"
FT BINDING 8
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27609419,
FT ECO:0007744|PDB:5B49"
FT BINDING 10
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27609419,
FT ECO:0007744|PDB:5B49"
FT BINDING 41
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27609419,
FT ECO:0007744|PDB:5B49"
FT BINDING 41
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27609419,
FT ECO:0007744|PDB:5B4C"
FT BINDING 79..80
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:27609419,
FT ECO:0007744|PDB:5B4B"
FT BINDING 79
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27609419,
FT ECO:0007744|PDB:5B4C"
FT BINDING 114
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27609419,
FT ECO:0007744|PDB:5B4C"
FT BINDING 122
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:27609419,
FT ECO:0007744|PDB:5B4B"
FT BINDING 157..167
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:27609419,
FT ECO:0007744|PDB:5B4B"
FT BINDING 195
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27609419,
FT ECO:0007744|PDB:5B4C"
FT BINDING 195
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:27609419,
FT ECO:0007744|PDB:5B4B"
FT BINDING 197
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27609419,
FT ECO:0007744|PDB:5B49"
FT MUTAGEN 10
FT /note="H->N: Does not bind to Mn 1."
FT /evidence="ECO:0000269|PubMed:27609419"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 16..28
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 54..68
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:5B4B"
FT TURN 79..83
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 86..92
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 123..132
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 135..142
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 146..164
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:5B4B"
FT HELIX 178..186
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 200..206
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 219..229
FT /evidence="ECO:0007829|PDB:5B4B"
FT STRAND 232..238
FT /evidence="ECO:0007829|PDB:5B4B"
SQ SEQUENCE 240 AA; 27555 MW; 0A1C8FD45E53B15E CRC64;
MSVLFISDLH LEAERPDITR AFLSFLDERA RRAEALYILG DFFEAWIGDD GMDAFQRSIA
QSLRQVADGG TRIYLMHGNR DFLIGKAFCR EAGCTLLPDP SVIDLYGEPV LLMHGDSLCT
RDEAYMRLRR WLRNPLTLWV LRHLPLATRH KLARKLRKES RAQTRMKAVD IIDVTPEEVP
RVMRGHGVRT LIHGHTHRPA EHPLDIDGQP ARRIVLGDWD RQGWALEIDA NGHRQAPFPL
