ETHA_MYCS2
ID ETHA_MYCS2 Reviewed; 492 AA.
AC A0R665; I7FUV7;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 94.
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=MSMEG_6440, MSMEI_6272;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
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:0000250|UniProtKB:P9WNF9, ECO:0000250|UniProtKB:Q7TVI2}.
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:0000250|UniProtKB:P9WNF9};
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 the transcriptional regulator EthR.
CC {ECO:0000250|UniProtKB:P9WNF9}.
CC -!- SIMILARITY: Belongs to the FAD-binding monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; CP000480; ABK75948.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP42698.1; -; Genomic_DNA.
DR RefSeq; WP_003897853.1; NZ_SIJM01000013.1.
DR RefSeq; YP_890653.1; NC_008596.1.
DR AlphaFoldDB; A0R665; -.
DR SMR; A0R665; -.
DR STRING; 246196.MSMEI_6272; -.
DR PRIDE; A0R665; -.
DR EnsemblBacteria; ABK75948; ABK75948; MSMEG_6440.
DR EnsemblBacteria; AFP42698; AFP42698; MSMEI_6272.
DR GeneID; 66737716; -.
DR KEGG; msg:MSMEI_6272; -.
DR KEGG; msm:MSMEG_6440; -.
DR PATRIC; fig|246196.19.peg.6265; -.
DR eggNOG; COG2072; Bacteria.
DR OMA; ASWTLKC; -.
DR OrthoDB; 324612at2; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; 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; IEA:InterPro.
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 3: Inferred from homology;
KW Cell membrane; FAD; Flavoprotein; Membrane; Monooxygenase; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..492
FT /note="FAD-containing monooxygenase EthA"
FT /id="PRO_0000398583"
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 492 AA; 55099 MW; A89FF49F0770A644 CRC64;
MTEHFDVVIV GAGISGISTA WHLQDRCPTK SYVILERRAN IGGTWDLFKY PGIRSDSDMF
TLGFRFKPWT SAKSIADGPS IWNYINEAAQ ENGIDKHIRT NHRVLGADWS DAENRWTITV
EADGEQKQIT ASFLSVCSGY YNYDQGYSPE FPGADDFAGQ IIHPQHWPED LDYAGKKIVV
IGSGATAVTL IPSLVNGGAA HVTMLQRSPT YIGSLPLVDP VAEKTNKYLP KNLAHFVNRW
KAIAFSTAQY QLARKFPNYM RKTLMTMAQR RLPEGFDVQK HFGPRYNPWD ERLCLAPNGD
LFKTIRAGKA DVVTDTIAKF TETGIKLTSG EELTADIIIT ATGLNMQLFG GASLTRNGQE
VDLTETMTYK GLMLSGVPNM AITFGYTNAS WTLKADLVSE FICRVLNYMD DNGFDRVEPQ
HPGDAVDALP FMDFNPGYFR RAMDSLPKSG SRAPWRLKQN YFFDLRMIRY DKVDEESLHF
TKHRAAVSAS SS
