PAGL_PSEAE
ID PAGL_PSEAE Reviewed; 173 AA.
AC Q9HVD1;
DT 26-JUN-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Lipid A deacylase PagL {ECO:0000303|PubMed:15611102, ECO:0000312|EMBL:AAG08048.1};
DE EC=3.1.1.77 {ECO:0000269|PubMed:15611102, ECO:0000269|PubMed:16352835, ECO:0000269|PubMed:16632613};
DE AltName: Full=LPS 3-O-deacylase PagL {ECO:0000303|PubMed:16632613};
DE AltName: Full=Outer membrane enzyme PagL {ECO:0000303|PubMed:16632613};
DE AltName: Full=PhoP/PhoQ-activated gene product L {ECO:0000303|PubMed:16632613};
DE Flags: Precursor;
GN Name=pagL {ECO:0000312|EMBL:AAG08048.1}; OrderedLocusNames=PA4661;
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] {ECO:0000312|EMBL:AAG08048.1}
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] {ECO:0000305}
RP PROTEIN SEQUENCE OF 24-28, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, DISRUPTION PHENOTYPE, ACTIVE SITE, AND MUTAGENESIS OF HIS-81;
RP SER-84; HIS-149 AND SER-151.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1 {ECO:0000269|PubMed:15611102};
RX PubMed=15611102; DOI=10.1074/jbc.m414235200;
RA Geurtsen J., Steeghs L., Hove J.T., van der Ley P., Tommassen J.;
RT "Dissemination of lipid A deacylases (pagL) among gram-negative bacteria:
RT identification of active-site histidine and serine residues.";
RL J. Biol. Chem. 280:8248-8259(2005).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1 {ECO:0000269|PubMed:16352835};
RX PubMed=16352835; DOI=10.1128/jb.188.1.191-201.2006;
RA Ernst R.K., Adams K.N., Moskowitz S.M., Kraig G.M., Kawasaki K.,
RA Stead C.M., Trent M.S., Miller S.I.;
RT "The Pseudomonas aeruginosa lipid A deacylase: selection for expression and
RT loss within the cystic fibrosis airway.";
RL J. Bacteriol. 188:191-201(2006).
RN [4] {ECO:0000305, ECO:0000312|PDB:2ERV}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 24-173, FUNCTION, CATALYTIC
RP ACTIVITY, REACTION MECHANISM, SUBUNIT, SUBCELLULAR LOCATION,
RP PHARMACEUTICAL, TOPOLOGY, ACTIVE SITE, SITE, AND MUTAGENESIS OF ASN-152;
RP ASN-159 AND GLU-163.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1 {ECO:0000269|PubMed:16632613};
RX PubMed=16632613; DOI=10.1073/pnas.0509392103;
RA Rutten L., Geurtsen J., Lambert W., Smolenaers J.J., Bonvin A.M.,
RA de Haan A., van der Ley P., Egmond M.R., Gros P., Tommassen J.;
RT "Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL
RT from Pseudomonas aeruginosa.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7071-7076(2006).
CC -!- FUNCTION: Has lipid A 3-O-deacylase activity. Hydrolyzes the ester bond
CC at the 3 position of lipid A, a bioactive component of
CC lipopolysaccharide (LPS), thereby releasing the primary fatty acyl
CC moiety. Lacks fatty acyl chain-length specificity as removes both 3-OH
CC C10 and 3-OH C14 fatty acids from lipid A.
CC {ECO:0000269|PubMed:15611102, ECO:0000269|PubMed:16352835,
CC ECO:0000269|PubMed:16632613}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-(acyloxy)acyl derivative of bacterial toxin + H2O = 3-
CC hydroxyacyl derivative of bacterial toxin + a fatty acid + H(+);
CC Xref=Rhea:RHEA:12032, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:136853, ChEBI:CHEBI:140675;
CC EC=3.1.1.77; Evidence={ECO:0000269|PubMed:15611102,
CC ECO:0000269|PubMed:16352835, ECO:0000269|PubMed:16632613};
CC -!- ACTIVITY REGULATION: Decreased activity at low temperatures (15 or 21
CC degrees Celsius). {ECO:0000269|PubMed:16352835}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16632613}.
CC -!- SUBCELLULAR LOCATION: Cell outer membrane {ECO:0000269|PubMed:15611102,
CC ECO:0000269|PubMed:16352835, ECO:0000269|PubMed:16632613}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:15611102,
CC ECO:0000269|PubMed:16352835, ECO:0000269|PubMed:16632613}.
CC -!- DISRUPTION PHENOTYPE: Has similar growth characteristics to wild-type
CC in LB medium at different temperatures (25, 30 or 37 degrees Celsius)
CC or in LB medium supplemented with 0-4 M sodium chloride, 0-1,500 ug/ml
CC chloramphenicol, 0-5% ethanol or 0-1% chloroform. Only when
CC chloramphenicol is present in the medium is a difference in the ability
CC to grow observed. The difference is most pronounced at a concentration
CC of 650 ug/ml chloramphenicol, where the absorbance of the wild-type
CC culture after overnight growth is 1.7-fold higher than that of the pagL
CC disruption mutant. {ECO:0000269|PubMed:15611102}.
CC -!- PHARMACEUTICAL: Might be useful for the development of new vaccines or
CC adjuvants because of its LPS-modifying properties. May be used for the
CC design of inhibitors with possible therapeutic value.
CC {ECO:0000303|PubMed:16632613}.
CC -!- SIMILARITY: Belongs to the PagL family. {ECO:0000305}.
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DR EMBL; AE004091; AAG08048.1; -; Genomic_DNA.
DR PIR; F83062; F83062.
DR RefSeq; NP_253350.1; NC_002516.2.
DR RefSeq; WP_003099307.1; NZ_QZGE01000029.1.
DR PDB; 2ERV; X-ray; 2.00 A; A/B=24-173.
DR PDBsum; 2ERV; -.
DR AlphaFoldDB; Q9HVD1; -.
DR SMR; Q9HVD1; -.
DR STRING; 287.DR97_1970; -.
DR PaxDb; Q9HVD1; -.
DR PRIDE; Q9HVD1; -.
DR EnsemblBacteria; AAG08048; AAG08048; PA4661.
DR GeneID; 881344; -.
DR KEGG; pae:PA4661; -.
DR PATRIC; fig|208964.12.peg.4883; -.
DR PseudoCAP; PA4661; -.
DR HOGENOM; CLU_093405_1_0_6; -.
DR OMA; AYTYWDG; -.
DR PhylomeDB; Q9HVD1; -.
DR BioCyc; PAER208964:G1FZ6-4757-MON; -.
DR EvolutionaryTrace; Q9HVD1; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0009279; C:cell outer membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0050528; F:acyloxyacyl hydrolase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0046493; P:lipid A metabolic process; IDA:UniProtKB.
DR GO; GO:0008653; P:lipopolysaccharide metabolic process; IDA:UniProtKB.
DR InterPro; IPR018550; Lipid-A_deacylase-rel.
DR InterPro; IPR011250; OMP/PagP_b-brl.
DR Pfam; PF09411; PagL; 1.
DR PIRSF; PIRSF029681; PagL; 1.
DR SUPFAM; SSF56925; SSF56925; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell outer membrane; Direct protein sequencing; Hydrolase;
KW Membrane; Pharmaceutical; Reference proteome; Signal; Transmembrane;
KW Transmembrane beta strand.
FT SIGNAL 1..23
FT /evidence="ECO:0000255, ECO:0000269|PubMed:15611102"
FT CHAIN 24..173
FT /note="Lipid A deacylase PagL"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:15611102"
FT /id="PRO_0000422912"
FT TOPO_DOM 25..28
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 29..32
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 33
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 34..49
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 50..56
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 57..71
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 72..73
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 74..89
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 90
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 91..93
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 94..95
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 96..98
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 99..100
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 101..115
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 116..117
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 118..128
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 129..138
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TRANSMEM 139..148
FT /note="Beta stranded"
FT /evidence="ECO:0000269|PubMed:16632613"
FT TOPO_DOM 149..173
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:16632613"
FT ACT_SITE 149
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:15611102"
FT ACT_SITE 151
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:15611102"
FT ACT_SITE 163
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:16632613"
FT SITE 152
FT /note="Critical for activity"
FT /evidence="ECO:0000269|PubMed:16632613"
FT MUTAGEN 81
FT /note="H->A,N: Does not affect LPS deacylation activity."
FT /evidence="ECO:0000269|PubMed:15611102"
FT MUTAGEN 84
FT /note="S->A,C: Does not affect LPS deacylation activity."
FT /evidence="ECO:0000269|PubMed:15611102"
FT MUTAGEN 149
FT /note="H->A,N: No deacylation of LPS."
FT /evidence="ECO:0000269|PubMed:15611102"
FT MUTAGEN 151
FT /note="S->A,C: No deacylation of LPS."
FT /evidence="ECO:0000269|PubMed:15611102"
FT MUTAGEN 152
FT /note="N->A: Inactive."
FT /evidence="ECO:0000269|PubMed:16632613"
FT MUTAGEN 159
FT /note="N->A: 304-fold reduction in activity."
FT /evidence="ECO:0000269|PubMed:16632613"
FT MUTAGEN 163
FT /note="E->A: 142-fold reduction in activity."
FT /evidence="ECO:0000269|PubMed:16632613"
FT STRAND 25..32
FT /evidence="ECO:0007829|PDB:2ERV"
FT STRAND 38..47
FT /evidence="ECO:0007829|PDB:2ERV"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:2ERV"
FT STRAND 58..71
FT /evidence="ECO:0007829|PDB:2ERV"
FT STRAND 78..93
FT /evidence="ECO:0007829|PDB:2ERV"
FT STRAND 96..116
FT /evidence="ECO:0007829|PDB:2ERV"
FT STRAND 124..137
FT /evidence="ECO:0007829|PDB:2ERV"
FT STRAND 142..151
FT /evidence="ECO:0007829|PDB:2ERV"
FT STRAND 162..172
FT /evidence="ECO:0007829|PDB:2ERV"
SQ SEQUENCE 173 AA; 18394 MW; 3B557C5787CD7B06 CRC64;
MKKLLPLAVL AALSSVHVAS AQAADVSAAV GATGQSGMTY RLGLSWDWDK SWWQTSTGRL
TGYWDAGYTY WEGGDEGAGK HSLSFAPVFV YEFAGDSIKP FIEAGIGVAA FSGTRVGDQN
LGSSLNFEDR IGAGLKFANG QSVGVRAIHY SNAGLKQPND GIESYSLFYK IPI
