ID   COR12_PAPSO             Reviewed;         321 AA.
AC   Q9SQ69;
DT   05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 71.
DE   RecName: Full=NADPH-dependent codeinone reductase 1-2;
DE            EC=1.1.1.247;
GN   Name=COR1.2;
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], PROTEIN SEQUENCE OF 130-135; 172-177; 233-243
RP   AND 245-248, FUNCTION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP   AND CATALYTIC ACTIVITY.
RX   PubMed=10417697; DOI=10.1046/j.1365-313x.1999.00470.x;
RA   Unterlinner B., Lenz R., Kutchan T.M.;
RT   "Molecular cloning and functional expression of codeinone reductase: the
RT   penultimate enzyme in morphine biosynthesis in the opium poppy Papaver
RT   somniferum.";
RL   Plant J. 18:465-475(1999).
RN   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=11079569;
RX   DOI=10.1002/1522-2683(20001001)21:16<3500::aid-elps3500>3.0.co;2-o;
RA   Decker G., Wanner G., Zenk M.H., Lottspeich F.;
RT   "Characterization of proteins in latex of the opium poppy (Papaver
RT   somniferum) using two-dimensional gel electrophoresis and
RT   microsequencing.";
RL   Electrophoresis 21:3500-3516(2000).
CC   -!- FUNCTION: Reduces codeinone to codeine in the penultimate step in
CC       morphine biosynthesis. Can use morphinone, hydrocodone and
CC       hydromorphone as substrate during reductive reaction with NADPH as
CC       cofactor, and morphine and dihydrocodeine as substrate during oxidative
CC       reaction with NADP as cofactor. {ECO:0000269|PubMed:10417697}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=codeine + NADP(+) = codeinone + H(+) + NADPH;
CC         Xref=Rhea:RHEA:19209, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:57871, ChEBI:CHEBI:58349, ChEBI:CHEBI:58473;
CC         EC=1.1.1.247; Evidence={ECO:0000269|PubMed:10417697};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=200 uM for codeine (at pH 9.0 and 30 degrees Celsius)
CC         {ECO:0000269|PubMed:10417697};
CC         KM=62 uM for codeinone (at pH 9.0 and 30 degrees Celsius)
CC         {ECO:0000269|PubMed:10417697};
CC         KM=220 uM for NADPH (at pH 9.0 and 30 degrees Celsius)
CC         {ECO:0000269|PubMed:10417697};
CC         KM=58 uM for NADP (at pH 9.0 and 30 degrees Celsius)
CC         {ECO:0000269|PubMed:10417697};
CC       pH dependence:
CC         Optimum pH is 6.8 for reduction (forward reaction) and 9.0 for
CC         oxidation (reverse reaction). {ECO:0000269|PubMed:10417697};
CC       Temperature dependence:
CC         Optimum temperature is 28 degrees Celsius for reduction (forward
CC         reaction) and 30 degrees Celsius for reduction (reverse reaction).
CC         {ECO:0000269|PubMed:10417697};
CC   -!- PATHWAY: Alkaloid biosynthesis; morphine biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11079569}.
CC       Note=Present in the cytosolic part of laticifer cells that secrete
CC       latex.
CC   -!- TISSUE SPECIFICITY: Latex secreting cells (laticifer cells). Expressed
CC       constitutively in all organs. {ECO:0000269|PubMed:10417697,
CC       ECO:0000269|PubMed:11079569}.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR   EMBL; AF108433; AAF13737.1; -; mRNA.
DR   AlphaFoldDB; Q9SQ69; -.
DR   SMR; Q9SQ69; -.
DR   UniPathway; UPA00852; -.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0047036; F:codeinone reductase (NADPH) activity; IDA:UniProtKB.
DR   GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR   GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR   CDD; cd19124; AKR_AKR4A_4B; 1.
DR   Gene3D; 3.20.20.100; -; 1.
DR   InterPro; IPR020471; AKR.
DR   InterPro; IPR044497; AKR4A/B.
DR   InterPro; IPR018170; Aldo/ket_reductase_CS.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   PIRSF; PIRSF000097; AKR; 1.
DR   PRINTS; PR00069; ALDKETRDTASE.
DR   SUPFAM; SSF51430; SSF51430; 1.
DR   PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR   PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR   PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE   1: Evidence at protein level;
KW   Alkaloid metabolism; Cytoplasm; Direct protein sequencing; NADP;
KW   Oxidoreductase.
FT   CHAIN           1..321
FT                   /note="NADPH-dependent codeinone reductase 1-2"
FT                   /id="PRO_0000418592"
FT   REGION          299..321
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        56
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   BINDING         119
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         214..273
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   SITE            86
FT                   /note="Lowers pKa of active site Tyr"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   321 AA;  35705 MW;  42491BF743327493 CRC64;
     MESNGVPMIT LSSGIRMPAL GMGTVETMEK GTEREKLAFL NAIEVGYRHF DTAAAYQSEE
     CLGEAIAEAL QLGLIKSRDE LFITSKLWCA DAHADLVLPA LQNSLRNLKL EYLDLYLIHH
     PVSLKPGKLV NEIPKDHILP MDYKSVWAAM EECQTLGFTR AIGVSNFSCK KLQELMATAK
     IPPVVNQVEM SPTLHQKNLR EYCKANNIMI TAHSVLGAIG APWGSNAVMD SKVLHQIAVA
     RGKSVAQVSM RWVYQQGASL VVKSFNEARM KENLKIFDSE LTAEDMEKIS EIPQSRTSSA
     DFLLSPTGPF KTEEEFWDEK D