D4N500 · DIOX1_PAPSO
- ProteinThebaine 6-O-demethylase
- GeneT6ODM
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids364 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Non-heme dioxygenase involved in biosynthesis of morphinan-type benzylisoquinoline and opiate alkaloids natural products (PubMed:20228795, PubMed:29779229).
Mediates the conversion of thebaine to neopinone (PubMed:20228795, PubMed:22098111).
Catalyzes also, with lower efficiency, the 6-O-demethylation of oripavine to neomorphinone, which is converted spontaneously to morphinone (PubMed:20228795, PubMed:29779229).
Supports dealkylation reactions such as O,O-demethylenation in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids; cleaves a methylenedioxy bridge leaving two hydroxyl groups (PubMed:23928311).
Catalyzes the O-demethylation of methylenedioxy bridges on protopine alkaloids such as allocryptopine (PubMed:23928311).
No activity with (S)-reticuline, salutaridine, papaverine, (S)-corytuberine, (S)-scoulerine, pavine, noscapine or codeine (PubMed:20228795).
Mediates the conversion of thebaine to neopinone (PubMed:20228795, PubMed:22098111).
Catalyzes also, with lower efficiency, the 6-O-demethylation of oripavine to neomorphinone, which is converted spontaneously to morphinone (PubMed:20228795, PubMed:29779229).
Supports dealkylation reactions such as O,O-demethylenation in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids; cleaves a methylenedioxy bridge leaving two hydroxyl groups (PubMed:23928311).
Catalyzes the O-demethylation of methylenedioxy bridges on protopine alkaloids such as allocryptopine (PubMed:23928311).
No activity with (S)-reticuline, salutaridine, papaverine, (S)-corytuberine, (S)-scoulerine, pavine, noscapine or codeine (PubMed:20228795).
Miscellaneous
Neopinone spontaneously rearranges to the more stable codeinone.
Catalytic activity
- thebaine + 2-oxoglutarate + O2 = neopinone + formaldehyde + succinate + CO2
- oripavine + 2-oxoglutarate + O2 = neomorphinone + formaldehyde + succinate + CO2
- (S)-canadine + S-adenosyl-L-methionine = (S)-cis-N-methylcanadine + S-adenosyl-L-homocysteine
- thebaine + 2-oxoglutarate + O2 = 6-O-demethylthebaine + formaldehyde + succinate + CO2 + H+
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 Fe2+ ion per subunit.
Activity regulation
Moderate substrate inhibition. Not inhibited in vitro by acylcyclohexanediones.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
15.4 μM | oripavine | |||||
20.3 μM | thebaine | |||||
16.4 μM | 2-oxoglutarate |
Pathway
Alkaloid biosynthesis; morphine biosynthesis.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 223 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 238 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 240 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 295 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 305 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 307 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | (S)-tetrahydroprotoberberine N-methyltransferase activity | |
Molecular Function | metal ion binding | |
Molecular Function | thebaine 6-O-demethylase activity | |
Biological Process | methylation | |
Biological Process | morphine biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameThebaine 6-O-demethylase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Viridiplantae > Streptophyta > Embryophyta > Tracheophyta > Spermatophyta > Magnoliopsida > Ranunculales > Papaveraceae > Papaveroideae > Papaver
Accessions
- Primary accessionD4N500
- Secondary accessions
Proteomes
Genome annotation databases
Phenotypes & Variants
Disruption phenotype
Accumulation of upstream metabolites, such as thebaine, but reduced production of morphine (PubMed:22098111).
Lower levels of sanguinarine and 1-benzylisoquinoline laudanosine and, to some extent, of noscapine and papaverine in roots but increased accumulation of the protopine alkaloids cryptopine, protopine and allocryptopine, and of the protoberberines sinactine, N-methystylopine, N-methylcanadine and rhoeadine N-methylporphyroxine (PubMed:23928311).
Lower levels of sanguinarine and 1-benzylisoquinoline laudanosine and, to some extent, of noscapine and papaverine in roots but increased accumulation of the protopine alkaloids cryptopine, protopine and allocryptopine, and of the protoberberines sinactine, N-methystylopine, N-methylcanadine and rhoeadine N-methylporphyroxine (PubMed:23928311).
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000401477 | 1-364 | Thebaine 6-O-demethylase | |||
Sequence: MEKAKLMKLGNGMEIPSVQELAKLTLAEIPSRYVCANENLLLPMGASVINDHETIPVIDIENLLSPEPIIGKLELDRLHFACKEWGFFQVVNHGVDASLVDSVKSEIQGFFNLSMDEKTKYEQEDGDVEGFGQGFIESEDQTLDWADIFMMFTLPLHLRKPHLFSKLPVPLRETIESYSSEMKKLSMVLFNKMEKALQVQAAEIKGMSEVFIDGTQAMRMNYYPPCPQPNLAIGLTSHSDFGGLTILLQINEVEGLQIKREGTWIAVKPLPNAFVVNVGDILEIMTNGIYHSVDHRAVVNSTNERLSIATFHDPSLESVIGPISSLITPETPALFKSGSTYGDLVEECKTRKLDGKSFLDSMRI |
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 214-314 | Fe2OG dioxygenase | ||||
Sequence: GTQAMRMNYYPPCPQPNLAIGLTSHSDFGGLTILLQINEVEGLQIKREGTWIAVKPLPNAFVVNVGDILEIMTNGIYHSVDHRAVVNSTNERLSIATFHDP |
Sequence similarities
Belongs to the iron/ascorbate-dependent oxidoreductase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length364
- Mass (Da)40,608
- Last updated2023-06-28 v2
- ChecksumD24D501698CB1A6E
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 266 | in Ref. 1; ADD85329 | ||||
Sequence: A → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
GQ500139 EMBL· GenBank· DDBJ | ADD85329.1 EMBL· GenBank· DDBJ | mRNA | ||
CM010716 EMBL· GenBank· DDBJ | RZC49697.1 EMBL· GenBank· DDBJ | Genomic DNA |