UniProtKB - P9WNF9 (ETHA_MYCTU)
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.
1 PublicationIs 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.
4 PublicationsCatalytic activityi
Cofactori
Activity regulationi
Kineticsi
- KM=194 µM for ethionamide1 Publication
- KM=340 µM for ethionamide1 Publication
- KM=10 µM for NADPH1 Publication
- KM=61 µM for phenylacetone1 Publication
- KM=520 µM for benzylacetone1 Publication
- KM=200 µM for 2-dodecanone1 Publication
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
- FAD binding Source: UniProtKB
- flavin adenine dinucleotide binding Source: UniProtKB
- N,N-dimethylaniline monooxygenase activity Source: MTBBASE
- NADPH binding Source: UniProtKB
- oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen Source: UniProtKB
- phenylacetone monooxygenase activity Source: UniProtKB
GO - Biological processi
- xenobiotic metabolic process Source: UniProtKB
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Ligand | FAD, Flavoprotein, NADP |
Enzyme and pathway databases
SABIO-RKi | P9WNF9 |
Names & Taxonomyi
Protein namesi | Recommended name: FAD-containing monooxygenase EthA1 Publication (EC:1.14.13.-1 Publication)Alternative name(s): Baeyer-Villiger monooxygenase EtaA1 Publication Short name: BVMO1 Publication Prodrug activator EtaA1 Publication |
Gene namesi | Name:ethA1 Publication Synonyms:etaA2 Publications Ordered Locus Names:Rv3854c |
Organismi | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Taxonomic identifieri | 83332 [NCBI] |
Taxonomic lineagei | Bacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex › |
Proteomesi |
|
Organism-specific databases
TubercuListi | Rv3854c |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication
Note: Is most likely membrane-associated.1 Publication
Cell Wall
- cell wall Source: MTBBASE
Cytosol
- cytosol Source: MTBBASE
Plasma Membrane
- plasma membrane Source: MTBBASE
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 84 | Y → C: ETH-resistant. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000398581 | 1 – 489 | FAD-containing monooxygenase EthAAdd BLAST | 489 |
Proteomic databases
PaxDbi | P9WNF9 |
Expressioni
Inductioni
Interactioni
Subunit structurei
Exists as a mixture of relatively large homooligomers ranging from 200 to 600 kDa.
1 PublicationProtein-protein interaction databases
STRINGi | 83332.Rv3854c |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | COG2072, Bacteria |
OMAi | ASWTLKC |
PhylomeDBi | P9WNF9 |
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 | AL123456 Genomic DNA Translation: CCP46683.1 |
PIRi | C70655 |
RefSeqi | NP_218371.1, NC_000962.3 WP_003899731.1, NZ_NVQJ01000057.1 |
Genome annotation databases
GeneIDi | 886175 |
KEGGi | mtu:Rv3854c |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP46683.1 |
PIRi | C70655 |
RefSeqi | NP_218371.1, NC_000962.3 WP_003899731.1, NZ_NVQJ01000057.1 |
3D structure databases
AlphaFoldDBi | P9WNF9 |
SMRi | P9WNF9 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 83332.Rv3854c |
Proteomic databases
PaxDbi | P9WNF9 |
Protocols and materials databases
DNASUi | 886175 |
Genome annotation databases
GeneIDi | 886175 |
KEGGi | mtu:Rv3854c |
Organism-specific databases
TubercuListi | Rv3854c |
Phylogenomic databases
eggNOGi | COG2072, Bacteria |
OMAi | ASWTLKC |
PhylomeDBi | P9WNF9 |
Enzyme and pathway databases
SABIO-RKi | P9WNF9 |
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_MYCTU | |
Accessioni | P9WNF9Primary (citable) accession number: P9WNF9 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 |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families