D4N500 · DIOX1_PAPSO

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).

Miscellaneous

Neopinone spontaneously rearranges to the more stable codeinone.

Catalytic activity

Cofactor

Protein has several cofactor binding sites:
L-ascorbate (UniProtKB | Rhea| CHEBI:38290 )

Fe cation (UniProtKB | Rhea| CHEBI:24875 )

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 μMoripavine
20.3 μMthebaine
16.4 μM2-oxoglutarate

Pathway

Alkaloid biosynthesis; morphine biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site2232-oxoglutarate (UniProtKB | ChEBI)
Binding site238Fe cation (UniProtKB | ChEBI)
Binding site240Fe cation (UniProtKB | ChEBI)
Binding site295Fe cation (UniProtKB | ChEBI)
Binding site3052-oxoglutarate (UniProtKB | ChEBI)
Binding site3072-oxoglutarate (UniProtKB | ChEBI)

GO annotations

AspectTerm
Molecular Function(S)-tetrahydroprotoberberine N-methyltransferase activity
Molecular Functionmetal ion binding
Molecular Functionthebaine 6-O-demethylase activity
Biological Processmethylation
Biological Processmorphine biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Thebaine 6-O-demethylase
  • EC number
  • Alternative names
    • Canadine demethylase
      (EC:2.1.1.-
      ) . EC:2.1.1.- (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      T6ODM
    • Synonyms
      DIOX1
    • ORF names
      C5167_018133

Organism names

  • Taxonomic identifier
  • Strain
    • cv. HN1
  • Taxonomic lineage
    Eukaryota > Viridiplantae > Streptophyta > Embryophyta > Tracheophyta > Spermatophyta > Magnoliopsida > Ranunculales > Papaveraceae > Papaveroideae > Papaver

Accessions

  • Primary accession
    D4N500
  • Secondary accessions
    • A0A4Y7ILV1

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).

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004014771-364Thebaine 6-O-demethylase

Expression

Tissue specificity

Mainly expressed in stems and leaves and, to a lower extent, in capsules and roots.

Developmental stage

In roots, repressed except during flowering (PubMed:29872026).
Accumulates in leaves and stems during flowering (PubMed:29872026).

Interaction

Protein-protein interaction databases

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain214-314Fe2OG dioxygenase

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    364
  • Mass (Da)
    40,608
  • Last updated
    2023-06-28 v2
  • Checksum
    D24D501698CB1A6E
MEKAKLMKLGNGMEIPSVQELAKLTLAEIPSRYVCANENLLLPMGASVINDHETIPVIDIENLLSPEPIIGKLELDRLHFACKEWGFFQVVNHGVDASLVDSVKSEIQGFFNLSMDEKTKYEQEDGDVEGFGQGFIESEDQTLDWADIFMMFTLPLHLRKPHLFSKLPVPLRETIESYSSEMKKLSMVLFNKMEKALQVQAAEIKGMSEVFIDGTQAMRMNYYPPCPQPNLAIGLTSHSDFGGLTILLQINEVEGLQIKREGTWIAVKPLPNAFVVNVGDILEIMTNGIYHSVDHRAVVNSTNERLSIATFHDPSLESVIGPISSLITPETPALFKSGSTYGDLVEECKTRKLDGKSFLDSMRI

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict266in Ref. 1; ADD85329

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
GQ500139
EMBL· GenBank· DDBJ
ADD85329.1
EMBL· GenBank· DDBJ
mRNA
CM010716
EMBL· GenBank· DDBJ
RZC49697.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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