ETHA_MYCBO
ID ETHA_MYCBO Reviewed; 489 AA.
AC Q7TVI2; A0A1R3Y5P0; X2BQ38;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=FAD-containing monooxygenase EthA;
DE EC=1.14.13.- {ECO:0000250|UniProtKB:P9WNF9};
DE AltName: Full=Baeyer-Villiger monooxygenase;
DE Short=BVMO;
DE AltName: Full=Prodrug activator EtaA;
GN Name=ethA; OrderedLocusNames=BQ2027_MB3884C;
OS Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=233413;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=12788972; DOI=10.1073/pnas.1130426100;
RA Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M.,
RA Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B.,
RA Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J.,
RA Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.;
RT "The complete genome sequence of Mycobacterium bovis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=28385856; DOI=10.1128/genomea.00157-17;
RA Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R.,
RA Robbe-Austerman S., Gordon S.V.;
RT "Updated reference genome sequence and annotation of Mycobacterium bovis
RT AF2122/97.";
RL Genome Announc. 5:E00157-E00157(2017).
RN [3]
RP FUNCTION AS AN ACTIVATOR OF THIOCARBAMIDE-CONTAINING DRUGS, COFACTOR,
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17220416; DOI=10.1128/aac.01063-06;
RA Dover L.G., Alahari A., Gratraud P., Gomes J.M., Bhowruth V.,
RA Reynolds R.C., Besra G.S., Kremer L.;
RT "EthA, a common activator of thiocarbamide-containing drugs acting on
RT different mycobacterial targets.";
RL Antimicrob. Agents Chemother. 51:1055-1063(2007).
CC -!- FUNCTION: Monooxygenase able to convert a wide range of ketones to the
CC corresponding esters or lactones via a Baeyer-Villiger oxidation
CC reaction. Can act on long-chain aliphatic ketones (2-hexanone to 2-
CC dodecanone) and on aromatic ketones (phenylacetone and benzylacetone).
CC Is also able to catalyze enantioselective sulfoxidation of methyl-p-
CC tolylsulfide. In vivo, likely functions as a BVMO, but the exact nature
CC of the physiological substrate(s) remains to be established.
CC {ECO:0000250|UniProtKB:P9WNF9}.
CC -!- FUNCTION: Is responsible for the activation of several thiocarbamide-
CC containing pro-drugs, such as ethionamide (ETH), isoxyl (ISO) and
CC thiacetazone (TAC), into reactive species.
CC {ECO:0000269|PubMed:17220416}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ethionamide + H(+) + NADPH + O2 = ethionamide S-oxide + H2O +
CC NADP(+); Xref=Rhea:RHEA:47616, ChEBI:CHEBI:4885, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87805;
CC Evidence={ECO:0000250|UniProtKB:P9WNF9};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:17220416};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P9WNF9};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P9WNF9}.
CC Note=Is most likely membrane-associated.
CC {ECO:0000250|UniProtKB:P9WNF9}.
CC -!- INDUCTION: Repressed by EthR. {ECO:0000269|PubMed:17220416}.
CC -!- DISRUPTION PHENOTYPE: Deletion of this gene leads to a strong
CC resistance to ETH, ISO and TAC. {ECO:0000269|PubMed:17220416}.
CC -!- SIMILARITY: Belongs to the FAD-binding monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; LT708304; SIU02516.1; -; Genomic_DNA.
DR RefSeq; NP_857521.1; NC_002945.3.
DR RefSeq; WP_003899731.1; NC_002945.4.
DR AlphaFoldDB; Q7TVI2; -.
DR SMR; Q7TVI2; -.
DR EnsemblBacteria; SIU02516; SIU02516; BQ2027_MB3884C.
DR PATRIC; fig|233413.5.peg.4255; -.
DR OMA; ASWTLKC; -.
DR Proteomes; UP000001419; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IMP:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 3.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR020946; Flavin_mOase-like.
DR Pfam; PF00743; FMO-like; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Cell membrane; FAD; Flavoprotein; Membrane; Monooxygenase; NADP;
KW Oxidoreductase.
FT CHAIN 1..489
FT /note="FAD-containing monooxygenase EthA"
FT /id="PRO_0000398582"
FT BINDING 15
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 44..47
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 54..56
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 56
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 104
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 183..189
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 207..208
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT SITE 292
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
SQ SEQUENCE 489 AA; 55326 MW; 844611B7E831180D CRC64;
MTEHLDVVIV GAGISGVSAA WHLQDRCPTK SYAILEKRES MGGTWDLFRY PGIRSDSDMY
TLGFRFRPWT GRQAIADGKP ILEYVKSTAA MYGIDRHIRF HHKVISADWS TAENRWTVHI
QSHGTLSALT CEFLFLCSGY YNYDEGYSPR FAGSEDFVGP IIHPQHWPED LDYDAKNIVV
IGSGATAVTL VPALADSGAK HVTMLQRSPT YIVSQPDRDG IAEKLNRWLP ETMAYTAVRW
KNVLRQAAVY SACQKWPRRM RKMFLSLIQR QLPEGYDVRK HFGPHYNPWD QRLCLVPNGD
LFRAIRHGKV EVVTDTIERF TATGIRLNSG RELPADIIIT ATGLNLQLFG GATATIDGQQ
VDITTTMAYK GMMLSGIPNM AYTVGYTNAS WTLKADLVSE FVCRLLNYMD DNGFDTVVVE
RPGSDVEERP FMEFTPGYVL RSLDELPKQG SRTPWRLNQN YLRDIRLIRR GKIDDEGLRF
AKRPAPVGV
