UniProtKB - P9WNF8 (ETHA_MYCTO)
FAD-containing monooxygenase EthA
ethA
Functioni
Monooxygenase able to convert a wide range of ketones to the corresponding esters or lactones via a Baeyer-Villiger oxidation reaction. Can act on long-chain aliphatic ketones (2-hexanone to 2-dodecanone) and on aromatic ketones (phenylacetone and benzylacetone). Is also able to catalyze enantioselective sulfoxidation of methyl-p-tolylsulfide. In vivo, likely functions as a BVMO, but the exact nature of the physiological substrate(s) remains to be established.
By similarityIs 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.
By similarityCatalytic activityi
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 15 | FADBy similarity | 1 | |
Binding sitei | 36 | FADBy similarity | 1 | |
Binding sitei | 56 | FADBy similarity | 1 | |
Binding sitei | 104 | FAD; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Sitei | 292 | Transition state stabilizerBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 44 – 47 | FADBy similarity | 4 | |
Nucleotide bindingi | 54 – 56 | NADPBy similarity | 3 | |
Nucleotide bindingi | 183 – 189 | NADPBy similarity | 7 | |
Nucleotide bindingi | 207 – 208 | NADPBy similarity | 2 |
GO - Molecular functioni
- flavin adenine dinucleotide binding Source: InterPro
- N,N-dimethylaniline monooxygenase activity Source: InterPro
- NADP binding Source: InterPro
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Ligand | FAD, Flavoprotein, NADP |
Names & Taxonomyi
Protein namesi | Recommended name: FAD-containing monooxygenase EthA (EC:1.14.13.-By similarity)Alternative name(s): Baeyer-Villiger monooxygenase EtaA Short name: BVMO Prodrug activator EtaA |
Gene namesi | Name:ethA Synonyms:etaA Ordered Locus Names:MT3969 |
Organismi | Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh) |
Taxonomic identifieri | 83331 [NCBI] |
Taxonomic lineagei | Bacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex › |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell membrane By similarity
Note: Is most likely membrane-associated.By similarity
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000427134 | 1 – 489 | FAD-containing monooxygenase EthAAdd BLAST | 489 |
Expressioni
Inductioni
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
HOGENOMi | CLU_032067_2_0_11 |
Family and domain databases
Gene3Di | 3.50.50.60, 3 hits |
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR020946, Flavin_mOase-like |
Pfami | View protein in Pfam PF00743, FMO-like, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MTEHLDVVIV GAGISGVSAA WHLQDRCPTK SYAILEKRES MGGTWDLFRY
60 70 80 90 100
PGIRSDSDMY TLGFRFRPWT GRQAIADGKP ILEYVKSTAA MYGIDRHIRF
110 120 130 140 150
HHKVISADWS TAENRWTVHI QSHGTLSALT CEFLFLCSGY YNYDEGYSPR
160 170 180 190 200
FAGSEDFVGP IIHPQHWPED LDYDAKNIVV IGSGATAVTL VPALADSGAK
210 220 230 240 250
HVTMLQRSPT YIVSQPDRDG IAEKLNRWLP ETMAYTAVRW KNVLRQAAVY
260 270 280 290 300
SACQKWPRRM RKMFLSLIQR QLPEGYDVRK HFGPHYNPWD QRLCLVPNGD
310 320 330 340 350
LFRAIRHGKV EVVTDTIERF TATGIRLNSG RELPADIIIT ATGLNLQLFG
360 370 380 390 400
GATATIDGQQ VDITTTMAYK GMMLSGIPNM AYTVGYTNAS WTLKADLVSE
410 420 430 440 450
FVCRLLNYMD DNGFDTVVVE RPGSDVEERP FMEFTPGYVL RSLDELPKQG
460 470 480
SRTPWRLNQN YLRDIRLIRR GKIDDEGLRF AKRPAPVGV
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AE000516 Genomic DNA Translation: AAK48336.1 |
PIRi | C70655 |
RefSeqi | WP_003899731.1, NZ_KK341227.1 |
Genome annotation databases
EnsemblBacteriai | AAK48336; AAK48336; MT3969 |
KEGGi | mtc:MT3969 |
PATRICi | fig|83331.31.peg.4268 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AE000516 Genomic DNA Translation: AAK48336.1 |
PIRi | C70655 |
RefSeqi | WP_003899731.1, NZ_KK341227.1 |
3D structure databases
AlphaFoldDBi | P9WNF8 |
SMRi | P9WNF8 |
ModBasei | Search... |
Genome annotation databases
EnsemblBacteriai | AAK48336; AAK48336; MT3969 |
KEGGi | mtc:MT3969 |
PATRICi | fig|83331.31.peg.4268 |
Phylogenomic databases
HOGENOMi | CLU_032067_2_0_11 |
Family and domain databases
Gene3Di | 3.50.50.60, 3 hits |
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR020946, Flavin_mOase-like |
Pfami | View protein in Pfam PF00743, FMO-like, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ETHA_MYCTO | |
Accessioni | P9WNF8Primary (citable) accession number: P9WNF8 Secondary accession number(s): L0TDR6, P96223, Q7D4Q8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2014 |
Last sequence update: | April 16, 2014 | |
Last modified: | May 25, 2022 | |
This is version 42 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |