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ethA

Gene
ethA
Protein
FAD-containing monooxygenase EthA
Organism
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
Length
492 amino acids
Function
Is responsible for the activation of several thiocarbamide-containing pro-drugs, such as ethionamide (ETH), isoxyl (ISO) and thiacetazone (TAC), into reactive species.
Similarity
Belongs to the FAD-binding monooxygenase family.
Mass
55.099 kDa
Sequence
MTEHFDVVIVGAGISGISTAWHLQDRCPTKSYVILERRANIGGTWDLFKYPGIRSDSDMFTLGFRFKPWTSAKSIADGPSIWNYINEAAQENGIDKHIRTNHRVLGADWSDAENRWTITVEADGEQKQITASFLSVCSGYYNYDQGYSPEFPGADDFAGQIIHPQHWPEDLDYAGKKIVVIGSGATAVTLIPSLVNGGAAHVTMLQRSPTYIGSLPLVDPVAEKTNKYLPKNLAHFVNRWKAIAFSTAQYQLARKFPNYMRKTLMTMAQRRLPEGFDVQKHFGPRYNPWDERLCLAPNGDLFKTIRAGKADVVTDTIAKFTETGIKLTSGEELTADIIITATGLNMQLFGGASLTRNGQEVDLTETMTYKGLMLSGVPNMAITFGYTNASWTLKADLVSEFICRVLNYMDDNGFDRVEPQHPGDAVDALPFMDFNPGYFRRAMDSLPKSGSRAPWRLKQNYFFDLRMIRYDKVDEESLHFTKHRAAVSASSS

Gene
ethA
Protein
FAD-containing monooxygenase EthA
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Length
489 amino acids
Function
Is responsible for the activation of several thiocarbamide-containing pro-drugs into cytotoxic species. Thus, catalyzes the oxidation of the antitubercular pro-drug ethionamide (ETH) to the corresponding sulfoxide, which is further oxidized by EthA to 2-ethyl-4-amidopyridine, presumably via the unstable doubly oxidized sulfinic acid intermediate; the final metabolite 2-ethyl-4-amidopyridine has no antitubercular activity, so the cytotoxic species is a metabolite intermediate formed by EthA. Also oxidizes thiacetazone (TAC), thiobenzamide, and isothionicotinamide and therefore is probably responsible, as suggested by the observation of crossover resistance, for the oxidative activation of these other thioamide antitubercular drugs.
Similarity
Belongs to the FAD-binding monooxygenase family.
Mass
55.326 kDa
Sequence
MTEHLDVVIVGAGISGVSAAWHLQDRCPTKSYAILEKRESMGGTWDLFRYPGIRSDSDMYTLGFRFRPWTGRQAIADGKPILEYVKSTAAMYGIDRHIRFHHKVISADWSTAENRWTVHIQSHGTLSALTCEFLFLCSGYYNYDEGYSPRFAGSEDFVGPIIHPQHWPEDLDYDAKNIVVIGSGATAVTLVPALADSGAKHVTMLQRSPTYIVSQPDRDGIAEKLNRWLPETMAYTAVRWKNVLRQAAVYSACQKWPRRMRKMFLSLIQRQLPEGYDVRKHFGPHYNPWDQRLCLVPNGDLFRAIRHGKVEVVTDTIERFTATGIRLNSGRELPADIIITATGLNLQLFGGATATIDGQQVDITTTMAYKGMMLSGIPNMAYTVGYTNASWTLKADLVSEFVCRLLNYMDDNGFDTVVVERPGSDVEERPFMEFTPGYVLRSLDELPKQGSRTPWRLNQNYLRDIRLIRRGKIDDEGLRFAKRPAPVGV

Gene
ethA
Protein
FAD-containing monooxygenase EthA
Organism
Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97)
Length
489 amino acids
Function
Is responsible for the activation of several thiocarbamide-containing pro-drugs, such as ethionamide (ETH), isoxyl (ISO) and thiacetazone (TAC), into reactive species.
Similarity
Belongs to the FAD-binding monooxygenase family.
Mass
55.326 kDa
Sequence
MTEHLDVVIVGAGISGVSAAWHLQDRCPTKSYAILEKRESMGGTWDLFRYPGIRSDSDMYTLGFRFRPWTGRQAIADGKPILEYVKSTAAMYGIDRHIRFHHKVISADWSTAENRWTVHIQSHGTLSALTCEFLFLCSGYYNYDEGYSPRFAGSEDFVGPIIHPQHWPEDLDYDAKNIVVIGSGATAVTLVPALADSGAKHVTMLQRSPTYIVSQPDRDGIAEKLNRWLPETMAYTAVRWKNVLRQAAVYSACQKWPRRMRKMFLSLIQRQLPEGYDVRKHFGPHYNPWDQRLCLVPNGDLFRAIRHGKVEVVTDTIERFTATGIRLNSGRELPADIIITATGLNLQLFGGATATIDGQQVDITTTMAYKGMMLSGIPNMAYTVGYTNASWTLKADLVSEFVCRLLNYMDDNGFDTVVVERPGSDVEERPFMEFTPGYVLRSLDELPKQGSRTPWRLNQNYLRDIRLIRRGKIDDEGLRFAKRPAPVGV

Gene
ethA
Protein
FAD-containing monooxygenase EthA
Organism
Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
Length
489 amino acids
Function
Is responsible for the activation of several thiocarbamide-containing pro-drugs into cytotoxic species. Thus, catalyzes the oxidation of the antitubercular pro-drug ethionamide (ETH) to the corresponding sulfoxide, which is further oxidized by EthA to 2-ethyl-4-amidopyridine, presumably via the unstable doubly oxidized sulfinic acid intermediate; the final metabolite 2-ethyl-4-amidopyridine has no antitubercular activity, so the cytotoxic species is a metabolite intermediate formed by EthA. Also oxidizes thiacetazone (TAC), thiobenzamide, and isothionicotinamide and thus is probably responsible, as suggested by the observation of crossover resistance, for the oxidative activation of these other thioamide antitubercular drugs.
Similarity
Belongs to the FAD-binding monooxygenase family.
Mass
55.326 kDa
Sequence
MTEHLDVVIVGAGISGVSAAWHLQDRCPTKSYAILEKRESMGGTWDLFRYPGIRSDSDMYTLGFRFRPWTGRQAIADGKPILEYVKSTAAMYGIDRHIRFHHKVISADWSTAENRWTVHIQSHGTLSALTCEFLFLCSGYYNYDEGYSPRFAGSEDFVGPIIHPQHWPEDLDYDAKNIVVIGSGATAVTLVPALADSGAKHVTMLQRSPTYIVSQPDRDGIAEKLNRWLPETMAYTAVRWKNVLRQAAVYSACQKWPRRMRKMFLSLIQRQLPEGYDVRKHFGPHYNPWDQRLCLVPNGDLFRAIRHGKVEVVTDTIERFTATGIRLNSGRELPADIIITATGLNLQLFGGATATIDGQQVDITTTMAYKGMMLSGIPNMAYTVGYTNASWTLKADLVSEFVCRLLNYMDDNGFDTVVVERPGSDVEERPFMEFTPGYVLRSLDELPKQGSRTPWRLNQNYLRDIRLIRRGKIDDEGLRFAKRPAPVGV