DIOX1_PAPSO
ID DIOX1_PAPSO Reviewed; 364 AA.
AC D4N500;
DT 30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Thebaine 6-O-demethylase;
DE EC=1.14.11.31 {ECO:0000269|PubMed:20228795};
GN Name=T6ODM; Synonyms=DIOX1;
OS Papaver somniferum (Opium poppy).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Ranunculales; Papaveraceae; Papaveroideae;
OC Papaver.
OX NCBI_TaxID=3469;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=20228795; DOI=10.1038/nchembio.317;
RA Hagel J.M., Facchini P.J.;
RT "Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis
RT in opium poppy.";
RL Nat. Chem. Biol. 6:273-275(2010).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH 2-OXOGLUTARATE.
RX PubMed=29408320; DOI=10.1016/j.jsb.2018.01.007;
RA Kluza A., Niedzialkowska E., Kurpiewska K., Wojdyla Z., Quesne M., Kot E.,
RA Porebski P.J., Borowski T.;
RT "Crystal structure of thebaine 6-O-demethylase from the morphine
RT biosynthesis pathway.";
RL J. Struct. Biol. 202:229-235(2018).
CC -!- FUNCTION: Non-heme dioxygenase catalyzing the conversion of thebaine to
CC neopinone. Catalyzes also, with lower efficiency, the 6-O-demethylation
CC of oripavine to morphinone. No activity with (S)-reticuline,
CC salutaridine, papaverine, (S)-corytuberine, (S)-scoulerine, pavine,
CC noscapine or codeine. {ECO:0000269|PubMed:20228795}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + thebaine = CO2 + formaldehyde +
CC neopinone + succinate; Xref=Rhea:RHEA:27477, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:59950, ChEBI:CHEBI:59953;
CC EC=1.14.11.31; Evidence={ECO:0000269|PubMed:20228795};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC Evidence={ECO:0000269|PubMed:20228795};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:20228795};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- ACTIVITY REGULATION: Moderate substrate inhibition. Not inhibited in
CC vitro by acylcyclohexanediones. {ECO:0000269|PubMed:20228795}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15.4 uM for oripavine {ECO:0000269|PubMed:20228795};
CC KM=20.3 uM for thebaine {ECO:0000269|PubMed:20228795};
CC KM=16.4 uM for 2-oxoglutarate {ECO:0000269|PubMed:20228795};
CC -!- PATHWAY: Alkaloid biosynthesis; morphine biosynthesis. {ECO:0000305}.
CC -!- MISCELLANEOUS: Neopinone spontaneously rearranges to the more stable
CC codeinone. {ECO:0000305|PubMed:20228795}.
CC -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; GQ500139; ADD85329.1; -; mRNA.
DR PDB; 5O7Y; X-ray; 1.97 A; A=1-364.
DR PDB; 5O9W; X-ray; 1.85 A; A=1-364.
DR PDBsum; 5O7Y; -.
DR PDBsum; 5O9W; -.
DR AlphaFoldDB; D4N500; -.
DR SMR; D4N500; -.
DR KEGG; ag:ADD85329; -.
DR SABIO-RK; D4N500; -.
DR UniPathway; UPA00852; -.
DR PRO; PR:D4N500; -.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0102804; F:oripavine 6-O-demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0102802; F:thebaine 6-O-demethylase activity; IDA:UniProtKB.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0097295; P:morphine biosynthetic process; IDA:UniProtKB.
DR Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR026992; DIOX_N.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR InterPro; IPR027443; IPNS-like_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR Pfam; PF14226; DIOX_N; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alkaloid metabolism; Dioxygenase; Iron; Metal-binding;
KW Methyltransferase; Oxidoreductase; Transferase.
FT CHAIN 1..364
FT /note="Thebaine 6-O-demethylase"
FT /id="PRO_0000401477"
FT DOMAIN 214..314
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 223
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:29408320,
FT ECO:0007744|PDB:5O9W"
FT BINDING 238
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 240
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 295
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 305
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805,
FT ECO:0000269|PubMed:29408320, ECO:0007744|PDB:5O9W"
FT BINDING 307
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:29408320,
FT ECO:0007744|PDB:5O9W"
FT HELIX 1..7
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 18..22
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 68..84
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 97..111
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 147..155
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 161..166
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 169..196
FT /evidence="ECO:0007829|PDB:5O9W"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 208..211
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 215..223
FT /evidence="ECO:0007829|PDB:5O9W"
FT TURN 229..231
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 242..249
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 280..285
FT /evidence="ECO:0007829|PDB:5O9W"
FT TURN 286..288
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 305..313
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 341..349
FT /evidence="ECO:0007829|PDB:5O9W"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:5O9W"
FT HELIX 358..361
FT /evidence="ECO:0007829|PDB:5O9W"
SQ SEQUENCE 364 AA; 40624 MW; 433749E8E12C8417 CRC64;
MEKAKLMKLG NGMEIPSVQE LAKLTLAEIP SRYVCANENL LLPMGASVIN DHETIPVIDI
ENLLSPEPII GKLELDRLHF ACKEWGFFQV VNHGVDASLV DSVKSEIQGF FNLSMDEKTK
YEQEDGDVEG FGQGFIESED QTLDWADIFM MFTLPLHLRK PHLFSKLPVP LRETIESYSS
EMKKLSMVLF NKMEKALQVQ AAEIKGMSEV FIDGTQAMRM NYYPPCPQPN LAIGLTSHSD
FGGLTILLQI NEVEGLQIKR EGTWISVKPL PNAFVVNVGD ILEIMTNGIY HSVDHRAVVN
STNERLSIAT FHDPSLESVI GPISSLITPE TPALFKSGST YGDLVEECKT RKLDGKSFLD
SMRI
