AQDC_MYCA9
ID AQDC_MYCA9 Reviewed; 269 AA.
AC B1MFK2;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=2-heptyl-3-hydroxy-4(1H)-quinolone dioxygenase {ECO:0000305|PubMed:28303132, ECO:0000305|PubMed:31228546};
DE Short=PQS dioxygenase {ECO:0000305|PubMed:28303132, ECO:0000305|PubMed:31228546};
DE EC=1.13.11.- {ECO:0000269|PubMed:28303132, ECO:0000269|PubMed:31228546};
GN Name=aqdC {ECO:0000303|PubMed:28303132, ECO:0000303|PubMed:31228546};
GN OrderedLocusNames=MAB_0303 {ECO:0000312|EMBL:CAM60402.1};
OS Mycobacteroides abscessus (strain ATCC 19977 / DSM 44196 / CIP 104536 / JCM
OS 13569 / NCTC 13031 / TMC 1543) (Mycobacterium abscessus).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacteroides; Mycobacteroides abscessus.
OX NCBI_TaxID=561007;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC
RC 1543;
RX PubMed=19543527; DOI=10.1371/journal.pone.0005660;
RA Ripoll F., Pasek S., Schenowitz C., Dossat C., Barbe V., Rottman M.,
RA Macheras E., Heym B., Herrmann J.L., Daffe M., Brosch R., Risler J.L.,
RA Gaillard J.L.;
RT "Non mycobacterial virulence genes in the genome of the emerging pathogen
RT Mycobacterium abscessus.";
RL PLoS ONE 4:E5660-E5660(2009).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND INDUCTION.
RC STRAIN=ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC
RC 1543;
RX PubMed=28303132; DOI=10.3389/fmicb.2017.00339;
RA Birmes F.S., Wolf T., Kohl T.A., Rueger K., Bange F., Kalinowski J.,
RA Fetzner S.;
RT "Mycobacterium abscessus subsp. abscessus Is Capable of Degrading
RT Pseudomonas aeruginosa Quinolone Signals.";
RL Front. Microbiol. 8:339-339(2017).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF WILD-TYPE APOENZYME AND IN COMPLEX
RP WITH N-OCTANOYLANTHRANILIC ACID AND MUTANT SER-96/ALA-246 IN COMPLEX WITH
RP PQS, FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, REACTION
RP MECHANISM, ACTIVE SITE, MUTAGENESIS OF ALA-96 AND HIS-246, AND SUBUNIT.
RC STRAIN=ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC
RC 1543;
RX PubMed=31228546; DOI=10.1016/j.jsb.2019.06.006;
RA Wullich S.C., Kobus S., Wienhold M., Hennecke U., Smits S.H.J., Fetzner S.;
RT "Structural basis for recognition and ring-cleavage of the Pseudomonas
RT quinolone signal (PQS) by AqdC, a mycobacterial dioxygenase of the
RT alpha/beta-hydrolase fold family.";
RL J. Struct. Biol. 207:287-294(2019).
CC -!- FUNCTION: Ring-cleaving dioxygenase involved in the degradation pathway
CC of the Pseudomonas aeruginosa quorum sensing signal molecules HHQ (2-
CC heptyl-4-quinolone) and PQS (2-heptyl-3-hydroxy-4(1H)-quinolone) to
CC anthranilate. Catalyzes the cleavage of PQS to form N-
CC octanoylanthranilate and carbon monoxide. Thus, leads to the
CC inactivation of PQS that plays a central role in the regulation of
CC virulence factor production by P.aeruginosa, thereby quenching the
CC production of antimicrobials, which may contribute to the
CC competitiveness of M.abscessus in presence of P.aeruginosa
CC (PubMed:31228546, PubMed:28303132). In vitro, can also use other 2-
CC alkyl-3-hydroxy-4(1H)-quinolone (AHQ) substrates with shorter alkyl
CC substituents at C2, but with lower efficiency (PubMed:31228546).
CC {ECO:0000269|PubMed:28303132, ECO:0000269|PubMed:31228546}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-heptyl-3-hydroxy-4(1H)-quinolone + O2 = CO + H(+) + N-
CC octanoylanthranilate; Xref=Rhea:RHEA:60352, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17245, ChEBI:CHEBI:29472,
CC ChEBI:CHEBI:143722; Evidence={ECO:0000269|PubMed:28303132,
CC ECO:0000269|PubMed:31228546};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60353;
CC Evidence={ECO:0000269|PubMed:28303132, ECO:0000305|PubMed:31228546};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=37.2 uM for 2-heptyl-3-hydroxy-4(1H)-quinolone
CC {ECO:0000269|PubMed:28303132};
CC KM=5.8 uM for 2-heptyl-3-hydroxy-4(1H)-quinolone
CC {ECO:0000269|PubMed:31228546};
CC KM=21.0 uM for 2-butyl-3-hydroxy-4(1H)-quinolone
CC {ECO:0000269|PubMed:31228546};
CC KM=963.8 uM for 2-methyl-3-hydroxy-4(1H)-quinolone
CC {ECO:0000269|PubMed:31228546};
CC Note=kcat is 97.8 sec(-1) with 2-heptyl-3-hydroxy-4(1H)-quinolone as
CC substrate (PubMed:28303132). kcat is 41.9 sec(-1) with 2-heptyl-3-
CC hydroxy-4(1H)-quinolone as substrate. kcat is 18.3 sec(-1) with 2-
CC butyl-3-hydroxy-4(1H)-quinolone as substrate. kcat is 1.63 sec(-1)
CC with 2-methyl-3-hydroxy-4(1H)-quinolone as substrate
CC (PubMed:31228546). {ECO:0000269|PubMed:28303132,
CC ECO:0000269|PubMed:31228546};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:31228546}.
CC -!- INDUCTION: Up-regulated by PQS. {ECO:0000269|PubMed:28303132}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. {ECO:0000305}.
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DR EMBL; CU458896; CAM60402.1; -; Genomic_DNA.
DR RefSeq; WP_005112966.1; NZ_MLCG01000005.1.
DR PDB; 6RA2; X-ray; 2.30 A; A/E/F=1-269.
DR PDB; 6RA3; X-ray; 2.00 A; A/E/F=1-269.
DR PDB; 6RB3; X-ray; 2.30 A; A/B/E=1-269.
DR PDBsum; 6RA2; -.
DR PDBsum; 6RA3; -.
DR PDBsum; 6RB3; -.
DR AlphaFoldDB; B1MFK2; -.
DR SMR; B1MFK2; -.
DR ESTHER; mycab-x8en65; HOD-cofactorfree-dioxygenase.
DR EnsemblBacteria; CAM60402; CAM60402; MAB_0303.
DR GeneID; 66970686; -.
DR KEGG; mab:MAB_0303; -.
DR OMA; AHASWIA; -.
DR Proteomes; UP000007137; Chromosome.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Oxidoreductase.
FT CHAIN 1..269
FT /note="2-heptyl-3-hydroxy-4(1H)-quinolone dioxygenase"
FT /id="PRO_0000448002"
FT ACT_SITE 246
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:31228546"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:31228546"
FT SITE 121
FT /note="Increases basicity of active site His"
FT /evidence="ECO:0000305|PubMed:31228546"
FT MUTAGEN 96
FT /note="A->S: Increases substrate affinity."
FT /evidence="ECO:0000269|PubMed:31228546"
FT MUTAGEN 246
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:31228546"
FT STRAND 3..7
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 10..17
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:6RA2"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 42..48
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 71..84
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 98..109
FT /evidence="ECO:0007829|PDB:6RA2"
FT TURN 111..113
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 129..137
FT /evidence="ECO:0007829|PDB:6RA2"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 144..156
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 162..170
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 177..194
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 197..202
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 223..232
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:6RA2"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:6RA2"
FT HELIX 253..266
FT /evidence="ECO:0007829|PDB:6RA2"
SQ SEQUENCE 269 AA; 29760 MW; 5013D9670F94423D CRC64;
MITTKTVNGV QIAFDDQGHE PGPVFVTLSG WAHDLRAYDG MLPYLRAAQR TVRVCWRGHG
PDRNLVGDFG IDEMAADTIG LLDALEVDSF VPIAHAHGGW AALEIADRLG AQRVPAVMIL
DLIMTPAPRE FVAALHGIQD PERWKEGRDG LVQSWLAGTT NQAVLDHVRY DSGGHGFDMW
ARAGRVIDEA YRTWGSPMRR MEALAEPCAI RHVFSHPKIG EYDALHDDFA ARHPWFSYRR
LGGETHFPGI ELPQQVAAEA IDLLAGARI
