C82X2_PAPSO
ID C82X2_PAPSO Reviewed; 554 AA.
AC I3PLR0;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2012, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=(S)-1-hydroxy-N-methylcanadine 13-hydroxylase CYP82X2 {ECO:0000305};
DE EC=1.14.14.163 {ECO:0000269|PubMed:25485687, ECO:0000269|PubMed:27378283};
DE AltName: Full=Cytochrome P450 82X2 {ECO:0000303|PubMed:22653730};
GN Name=CYP82X2 {ECO:0000303|PubMed:22653730};
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 [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=22653730; DOI=10.1126/science.1220757;
RA Winzer T., Gazda V., He Z., Kaminski F., Kern M., Larson T.R., Li Y.,
RA Meade F., Teodor R., Vaistij F.E., Walker C., Bowser T.A., Graham I.A.;
RT "A Papaver somniferum 10-gene cluster for synthesis of the anticancer
RT alkaloid noscapine.";
RL Science 336:1704-1708(2012).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25485687; DOI=10.1038/nchembio.1717;
RA Dang T.T., Chen X., Facchini P.J.;
RT "Acetylation serves as a protective group in noscapine biosynthesis in
RT opium poppy.";
RL Nat. Chem. Biol. 11:104-106(2015).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27378283; DOI=10.1038/ncomms12137;
RA Li Y., Smolke C.D.;
RT "Engineering biosynthesis of the anticancer alkaloid noscapine in yeast.";
RL Nat. Commun. 7:12137-12137(2016).
RN [4]
RP FUNCTION.
RX PubMed=29610307; DOI=10.1073/pnas.1721469115;
RA Li Y., Li S., Thodey K., Trenchard I., Cravens A., Smolke C.D.;
RT "Complete biosynthesis of noscapine and halogenated alkaloids in yeast.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E3922-E3931(2018).
CC -!- FUNCTION: Cytochrome P450 involved in the biosynthesis of the
CC benzylisoquinoline alkaloid noscapine (PubMed:25485687,
CC PubMed:27378283, PubMed:29610307). Converts (S)-1-hydroxy-N-
CC methylcanadine to (13S,14R)-1,13-dihydroxy-N-methylcanadine
CC (PubMed:25485687, PubMed:27378283). {ECO:0000269|PubMed:25485687,
CC ECO:0000269|PubMed:27378283, ECO:0000269|PubMed:29610307}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-1-hydroxy-N-methylcanadine + O2 + reduced [NADPH--
CC hemoprotein reductase] = (13S,14R)-1,13-dihydroxy-N-methylcanadine +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:57380, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:141633,
CC ChEBI:CHEBI:141639; EC=1.14.14.163;
CC Evidence={ECO:0000269|PubMed:25485687, ECO:0000269|PubMed:27378283};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57381;
CC Evidence={ECO:0000305|PubMed:25485687};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q96242};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.6 uM for (S)-1-hydroxy-N-methylcanadine
CC {ECO:0000269|PubMed:25485687};
CC Vmax=34.7 nmol/min/mg enzyme with (S)-1-hydroxy-N-methylcanadine as
CC substrate {ECO:0000269|PubMed:25485687};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in capsules (PubMed:22653730).
CC Expressed is stems (PubMed:22653730). {ECO:0000269|PubMed:22653730}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; JQ659004; AFB74616.1; -; Genomic_DNA.
DR AlphaFoldDB; I3PLR0; -.
DR SMR; I3PLR0; -.
DR EnsemblPlants; RZC84730; RZC84730; C5167_047514.
DR Gramene; RZC84730; RZC84730; C5167_047514.
DR KEGG; ag:AFB74616; -.
DR BioCyc; MetaCyc:MON-17769; -.
DR BRENDA; 1.14.14.163; 4515.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0033075; P:isoquinoline alkaloid biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..554
FT /note="(S)-1-hydroxy-N-methylcanadine 13-hydroxylase
FT CYP82X2"
FT /id="PRO_0000447597"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 494
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:Q96242"
SQ SEQUENCE 554 AA; 62705 MW; 5619F375C0D96CE3 CRC64;
MKSLMMNKLL FLQRITDSPS TTIISTFIVT IISIVFLYTV LLIRTTKNKQ KIAAPKASGA
WPFIGHLKLF MKQDTQFYRT LGTMSDKYGS VFTLRLGNQA ILVVSNWEMV KECFTTNDKS
FSNRPSTLST KYMLNDTNSV VFSPYGTYWR EMRKILVQKL LISNQRSEAL KNLKTKEIDN
SFVKLNDLCN NDVSGGGTKV RMDEWLADMM FNIIARITFG YQSGGGDAPG ASTTSKNVER
YKKTLDEMFV VLATRFAVSD IFPSLEFIDR LRGLVKDMKI LGDELNSIAG CFIEEHRQKR
RESLSSLLSL SNESVGDEQD FIDVLLSIMD QSRLPGDDPD FIIKIMILEA FAGGTDSLSA
TLTWVLSLLL NHPNVLKRAR EEIDRHVENG KQVEVSDIPK LGYIDAIIKE TMRLYPVGAL
SERYTTEECE VGRFNVPAGT RLLVNIWKIH RDPSVWENPS DFQPERFLCS DKVGVDLYGQ
NYELIPFGAG RRVCPAIVSS LQTMHYALAR LIQGYEMKSA SLDGKVNMEE MIAMSCHKMS
PLEVIISPRE PRRS
