PQSD_PSEAE
ID PQSD_PSEAE Reviewed; 337 AA.
AC P20582;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 08-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Anthraniloyl-CoA anthraniloyltransferase {ECO:0000305};
DE EC=2.3.1.262 {ECO:0000269|PubMed:18728009, ECO:0000269|PubMed:19694421, ECO:0000269|PubMed:21425231, ECO:0000269|PubMed:22992202};
DE AltName: Full=2-heptyl-4(1H)-quinolone synthase PqsD {ECO:0000305};
DE Short=PqsD {ECO:0000305};
GN Name=pqsD; OrderedLocusNames=PA0999;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 109-337.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=2153661; DOI=10.1128/jb.172.2.884-900.1990;
RA Essar D.W., Eberly L., Hadero A., Crawford I.P.;
RT "Identification and characterization of genes for a second anthranilate
RT synthase in Pseudomonas aeruginosa: interchangeability of the two
RT anthranilate synthases and evolutionary implications.";
RL J. Bacteriol. 172:884-900(1990).
RN [3]
RP FUNCTION, ACTIVE SITE, IDENTIFICATION BY MASS SPECTROMETRY, DISRUPTION
RP PHENOTYPE, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1 {ECO:0000303|PubMed:18728009};
RX PubMed=18728009; DOI=10.1074/jbc.m804555200;
RA Zhang Y.M., Frank M.W., Zhu K., Mayasundari A., Rock C.O.;
RT "PqsD is responsible for the synthesis of 2,4-dihydroxyquinoline, an
RT extracellular metabolite produced by Pseudomonas aeruginosa.";
RL J. Biol. Chem. 283:28788-28794(2008).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21425231; DOI=10.1002/cbic.201100014;
RA Pistorius D., Ullrich A., Lucas S., Hartmann R.W., Kazmaier U., Mueller R.;
RT "Biosynthesis of 2-Alkyl-4(1H)-quinolones in Pseudomonas aeruginosa:
RT potential for therapeutic interference with pathogenicity.";
RL ChemBioChem 12:850-853(2011).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22992202; DOI=10.1021/ja3072397;
RA Storz M.P., Maurer C.K., Zimmer C., Wagner N., Brengel C., de Jong J.C.,
RA Lucas S., Muesken M., Haeussler S., Steinbach A., Hartmann R.W.;
RT "Validation of PqsD as an anti-biofilm target in Pseudomonas aeruginosa by
RT development of small-molecule inhibitors.";
RL J. Am. Chem. Soc. 134:16143-16146(2012).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24239007; DOI=10.1016/j.chembiol.2013.09.021;
RA Dulcey C.E., Dekimpe V., Fauvelle D.A., Milot S., Groleau M.C., Doucet N.,
RA Rahme L.G., Lepine F., Deziel E.;
RT "The end of an old hypothesis: the Pseudomonas signaling molecules 4-
RT hydroxy-2-alkylquinolines derive from fatty acids, not 3-ketofatty acids.";
RL Chem. Biol. 20:1481-1491(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 2-337 IN COMPLEX WITH
RP ANTHRANILOYL-COA, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, MUTAGENESIS OF
RP CYS-113, AND ACTIVE SITE.
RX PubMed=19694421; DOI=10.1021/bi9009055;
RA Bera A.K., Atanasova V., Robinson H., Eisenstein E., Coleman J.P.,
RA Pesci E.C., Parsons J.F.;
RT "Structure of PqsD, a Pseudomonas quinolone signal biosynthetic enzyme, in
RT complex with anthranilate.";
RL Biochemistry 48:8644-8655(2009).
CC -!- FUNCTION: Required for the biosynthesis of a number of signaling
CC molecules, such as the quinolone signal 2-heptyl-3-hydroxy-4(1H)-
CC quinolone (PQS), 2-heptyl-4-hydroxyquinoline (HHQ) and 2,4-
CC dihydroxyquinoline (DHQ). These molecules are required for normal
CC biofilm formation. Catalyzes the transfer of the anthraniloyl moiety
CC from anthraniloyl-CoA to malonyl-CoA to form 2-aminobenzoylacetyl-CoA
CC (PubMed:24239007). The first step of the reaction is the formation of a
CC covalent anthraniloyl-PqsD intermediate (PubMed:18728009,
CC PubMed:19694421). Next, the short-lived intermediate 3-(2-aminophenyl)-
CC 3-oxopropanoyl-CoA is formed. An intramolecular rearrangement of this
CC intermediate can give rise to 2,4-dihydroxyquinoline (DHQ).
CC {ECO:0000269|PubMed:18728009, ECO:0000269|PubMed:19694421,
CC ECO:0000269|PubMed:21425231, ECO:0000269|PubMed:22992202,
CC ECO:0000269|PubMed:24239007}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=anthraniloyl-CoA + H(+) + malonyl-CoA = (2-
CC aminobenzoyl)acetyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:50472,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57331, ChEBI:CHEBI:57384, ChEBI:CHEBI:131447;
CC EC=2.3.1.262; Evidence={ECO:0000269|PubMed:18728009,
CC ECO:0000269|PubMed:19694421, ECO:0000269|PubMed:21425231,
CC ECO:0000269|PubMed:22992202, ECO:0000269|PubMed:24239007};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=35 uM for anthraniloyl-CoA {ECO:0000269|PubMed:18728009};
CC KM=104 uM for malonyl-CoA {ECO:0000269|PubMed:18728009};
CC KM=48.7 uM for malonyl-CoA {ECO:0000269|PubMed:21425231};
CC KM=18 uM for malonyl-ACP {ECO:0000269|PubMed:18728009};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19694421}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the biosynthesis of the signaling
CC molecules 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), 2-heptyl-4-
CC hydroxyquinoline (HHQ) and 2,4-dihydroxyquinoline (DHQ).
CC {ECO:0000269|PubMed:18728009}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. FabH family.
CC {ECO:0000305}.
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DR EMBL; AE004091; AAG04388.1; -; Genomic_DNA.
DR EMBL; M33810; AAA88446.1; -; Genomic_DNA.
DR PIR; B83522; B83522.
DR PIR; D35116; D35116.
DR RefSeq; NP_249690.1; NC_002516.2.
DR RefSeq; WP_003112550.1; NZ_QZGE01000006.1.
DR PDB; 3H76; X-ray; 1.80 A; A/B=2-337.
DR PDB; 3H77; X-ray; 1.80 A; A/B=2-337.
DR PDB; 3H78; X-ray; 1.70 A; A/B=2-337.
DR PDBsum; 3H76; -.
DR PDBsum; 3H77; -.
DR PDBsum; 3H78; -.
DR AlphaFoldDB; P20582; -.
DR SMR; P20582; -.
DR STRING; 287.DR97_948; -.
DR PaxDb; P20582; -.
DR PRIDE; P20582; -.
DR DNASU; 880625; -.
DR EnsemblBacteria; AAG04388; AAG04388; PA0999.
DR GeneID; 880625; -.
DR KEGG; pae:PA0999; -.
DR PATRIC; fig|208964.12.peg.1031; -.
DR PseudoCAP; PA0999; -.
DR HOGENOM; CLU_039592_4_1_6; -.
DR InParanoid; P20582; -.
DR OMA; DIRQQCT; -.
DR PhylomeDB; P20582; -.
DR BioCyc; MetaCyc:MON-16011; -.
DR BioCyc; PAER208964:G1FZ6-1018-MON; -.
DR BRENDA; 2.3.1.230; 5087.
DR BRENDA; 2.3.1.262; 5087.
DR SABIO-RK; P20582; -.
DR EvolutionaryTrace; P20582; -.
DR PHI-base; PHI:3522; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016746; F:acyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR013751; ACP_syn_III.
DR InterPro; IPR013747; ACP_syn_III_C.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF08545; ACP_syn_III; 1.
DR Pfam; PF08541; ACP_syn_III_C; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cytoplasm; Reference proteome; Transferase.
FT CHAIN 1..337
FT /note="Anthraniloyl-CoA anthraniloyltransferase"
FT /id="PRO_0000110519"
FT ACT_SITE 113
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000269|PubMed:18728009,
FT ECO:0000269|PubMed:19694421"
FT BINDING 29
FT /ligand="anthraniloyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57331"
FT /evidence="ECO:0000269|PubMed:19694421"
FT BINDING 33
FT /ligand="anthraniloyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57331"
FT /evidence="ECO:0000269|PubMed:19694421"
FT BINDING 154..155
FT /ligand="anthraniloyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57331"
FT /evidence="ECO:0000269|PubMed:19694421"
FT BINDING 221..224
FT /ligand="anthraniloyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57331"
FT /evidence="ECO:0000269|PubMed:19694421"
FT BINDING 258
FT /ligand="anthraniloyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57331"
FT /evidence="ECO:0000269|PubMed:19694421"
FT MUTAGEN 113
FT /note="C->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:19694421"
FT STRAND 5..12
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 15..19
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 20..23
FT /evidence="ECO:0007829|PDB:3H78"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 31..38
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 53..66
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 91..99
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 115..128
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 133..142
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:3H78"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 154..157
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 162..170
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 175..186
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 188..193
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 209..213
FT /evidence="ECO:0007829|PDB:3H78"
FT TURN 214..217
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:3H76"
FT HELIX 223..244
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 262..272
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 283..286
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 293..301
FT /evidence="ECO:0007829|PDB:3H78"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 310..317
FT /evidence="ECO:0007829|PDB:3H78"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:3H78"
FT STRAND 321..328
FT /evidence="ECO:0007829|PDB:3H78"
SQ SEQUENCE 337 AA; 36379 MW; BB887BAED9C19B92 CRC64;
MGNPILAGLG FSLPKRQVSN HDLVGRINTS DEFIVERTGV RTRYHVEPEQ AVSALMVPAA
RQAIEAAGLL PEDIDLLLVN TLSPDHHDPS QACLIQPLLG LRHIPVLDIR AQCSGLLYGL
QMARGQILAG LARHVLVVCG EVLSKRMDCS DRGRNLSILL GDGAGAVVVS AGESLEDGLL
DLRLGADGNY FDLLMTAAPG SASPTFLDEN VLREGGGEFL MRGRPMFEHA SQTLVRIAGE
MLAAHELTLD DIDHVICHQP NLRILDAVQE QLGIPQHKFA VTVDRLGNMA SASTPVTLAM
FWPDIQPGQR VLVLTYGSGA TWGAALYRKP EEVNRPC
