ID   STORR_PAPSO             Reviewed;         901 AA.
AC   P0DKI7; A0A0H4BL73;
DT   14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT   14-OCT-2015, sequence version 1.
DT   03-AUG-2022, entry version 24.
DE   RecName: Full=Bifunctional protein STORR {ECO:0000303|PubMed:26113639};
DE   AltName: Full=(S)- to (R)-reticuline {ECO:0000303|PubMed:26113639};
DE   Includes:
DE     RecName: Full=Cytochrome P450 82Y2 {ECO:0000303|PubMed:26113639};
DE              EC=1.14.19.54 {ECO:0000269|PubMed:26113639};
DE     AltName: Full=1,2-dehydroreticuline synthase {ECO:0000305};
DE     AltName: Full=CYP82Y2 {ECO:0000303|PubMed:26113639};
DE   Includes:
DE     RecName: Full=Oxydoreductase {ECO:0000303|PubMed:26113639};
DE              EC=1.5.1.27 {ECO:0000269|PubMed:26113639};
DE     AltName: Full=1,2-dehydroreticulinium reductase (NADPH) {ECO:0000305};
GN   Name=STORR {ECO:0000303|PubMed:26113639};
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], IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION,
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP   GLY-550.
RC   STRAIN=cv. HM2;
RX   PubMed=26113639; DOI=10.1126/science.aab1852;
RA   Winzer T., Kern M., King A.J., Larson T.R., Teodor R.I., Donninger S.L.,
RA   Li Y., Dowle A.A., Cartwright J., Bates R., Ashford D., Thomas J.,
RA   Walker C., Bowser T.A., Graham I.A.;
RT   "Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase
RT   fusion protein.";
RL   Science 349:309-312(2015).
CC   -!- FUNCTION: Bifunctional protein involved in the biosynthesis of
CC       morphinan-type benzylisoquinoline alkaloids. Required for the
CC       isomerization of (S)- to (R)-reticuline. The cytochrome P450 module is
CC       responsible for the conversion of (S)-reticuline to 1,2-
CC       dehydroreticuline while the oxidoreductase module converts 1,2-
CC       dehydroreticuline to (R)-reticuline. {ECO:0000269|PubMed:26113639}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(R)-reticuline + NADP(+) = 1,2-dehydroreticuline + H(+) +
CC         NADPH; Xref=Rhea:RHEA:17569, ChEBI:CHEBI:15378, ChEBI:CHEBI:18363,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58144, ChEBI:CHEBI:58349; EC=1.5.1.27;
CC         Evidence={ECO:0000269|PubMed:26113639};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-reticuline + O2 + reduced [NADPH--hemoprotein reductase] =
CC         1,2-dehydroreticuline + H(+) + 2 H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:56308, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:18363, ChEBI:CHEBI:57618, ChEBI:CHEBI:57873,
CC         ChEBI:CHEBI:58210; EC=1.14.19.54;
CC         Evidence={ECO:0000269|PubMed:26113639};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=13 uM for (S)-reticuline {ECO:0000269|PubMed:26113639};
CC         KM=14 uM for 1,2-dehydroreticuline {ECO:0000269|PubMed:26113639};
CC   -!- PATHWAY: Alkaloid biosynthesis; morphine biosynthesis. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the cytochrome P450
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the aldo/keto
CC       reductase family. {ECO:0000305}.
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DR   EMBL; KP998574; AKN63431.1; -; mRNA.
DR   AlphaFoldDB; P0DKI7; -.
DR   SMR; P0DKI7; -.
DR   BRENDA; 1.14.19.54; 4515.
DR   BRENDA; 1.5.1.27; 4515.
DR   UniPathway; UPA00852; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0047128; F:1,2-dehydroreticulinium reductase (NADPH) activity; IEA:UniProtKB-EC.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:InterPro.
DR   GO; GO:0016717; F:oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water; IDA:UniProtKB.
DR   GO; GO:0016646; F:oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor; IDA:UniProtKB.
DR   GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR   GO; GO:0097295; P:morphine biosynthetic process; IMP:UniProtKB.
DR   CDD; cd19124; AKR_AKR4A_4B; 1.
DR   Gene3D; 1.10.630.10; -; 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; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00069; ALDKETRDTASE.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   SUPFAM; SSF51430; SSF51430; 1.
DR   PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR   PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Alkaloid metabolism; Heme; Iron; Membrane; Metal-binding;
KW   Multifunctional enzyme; NADP; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..901
FT                   /note="Bifunctional protein STORR"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000433977"
FT   TRANSMEM        12..32
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         513
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
FT   MUTAGEN         550
FT                   /note="G->R: In storr-3; accumulates (S)-reticuline but not
FT                   1,2-dehydroreticuline."
FT                   /evidence="ECO:0000269|PubMed:26113639"
SQ   SEQUENCE   901 AA;  100653 MW;  6B2CF4A2BE55B149 CRC64;
     MELQYISYFQ PTSSVVALLL ALVSILSSVV VLRKTFLNNY SSSPASSTKT AVLSHQRQQS
     CALPISGLLH IFMNKNGLIH VTLGNMADKY GPIFSFPTGS HRTLVVSSWE MVKECFTGNN
     DTAFSNRPIP LAFKTIFYAC GGIDSYGLSS VPYGKYWREL RKVCVHNLLS NQQLLKFRHL
     IISQVDTSFN KLYELCKNSE DNHGNYTTTT TTAAGMVRID DWLAELSFNV IGRIVCGFQS
     GPKTGAPSRV EQFKEAINEA SYFMSTSPVS DNVPMLGWID QLTGLTRNMK HCGKKLDLVV
     ESIINDHRQK RRFSRTKGGD EKDDEQDDFI DICLSIMEQP QLPGNNNPSQ IPIKSIVLDM
     IGGGTDTTKL TTIWTLSLLL NNPHVLDKAK QEVDAHFRTK RRSTNDAAAA VVDFDDIRNL
     VYIQAIIKES MRLYPASPVV ERLSGEDCVV GGFHVPAGTR LWANVWKMQR DPKVWDDPLV
     FRPDRFLSDE QKMVDVRGQN YELLPFGAGR RVCPGVSFSL DLMQLVLTRL ILEFEMKSPS
     GKVDMTATPG LMSYKVIPLD ILLTHRRIKP CVQSAASERD MESSGVPVIT LGSGKVMPVL
     GMGTFEKVGK GSERERLAIL KAIEVGYRYF DTAAAYETEE VLGEAIAEAL QLGLVKSRDE
     LFISSMLWCT DAHADRVLLA LQNSLRNLKL EYVDLYMLPF PASLKPGKIT MDIPEEDICR
     MDYRSVWAAM EECQNLGFTK SIGVSNFSCK KLQELMATAN IPPAVNQVEM SPAFQQKKLR
     EYCNANNILV SAISVLGSNG TPWGSNAVLG SEVLKKIAMA KGKSVAQVSM RWVYEQGASL
     VVKSFSEERL RENLNIFDWE LTKEDHEKIG EIPQCRILSA YFLVSPNGPF KSQEELWDDE
     A