ID   V19H_CATRO              Reviewed;         506 AA.
AC   P0DO22; A0A4Y5RUI6;
DT   13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2019, sequence version 1.
DT   03-AUG-2022, entry version 6.
DE   RecName: Full=(+)-vincadifformine 19-hydroxylase {ECO:0000303|PubMed:31009114};
DE            EC=1.14.14.- {ECO:0000269|PubMed:31009114};
DE   AltName: Full=Cytochrome P450 V19H {ECO:0000305};
GN   Name=V19H {ECO:0000303|PubMed:31009114};
OS   Catharanthus roseus (Madagascar periwinkle) (Vinca rosea).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; lamiids; Gentianales; Apocynaceae; Rauvolfioideae; Vinceae;
OC   Catharanthinae; Catharanthus.
OX   NCBI_TaxID=4058;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX   PubMed=31009114; DOI=10.1111/tpj.14346;
RA   Williams D., Qu Y., Simionescu R., De Luca V.;
RT   "The assembly of (+)-vincadifformine- and (-)-tabersonine-derived
RT   monoterpenoid indole alkaloids in Catharanthus roseus involves separate
RT   branch pathways.";
RL   Plant J. 99:626-636(2019).
CC   -!- FUNCTION: Component of the monoterpenoid indole alkaloids (MIAs, e.g.
CC       echitovenine, tabersonine, lochnericine, 19-hydroxytabersonine and
CC       horhammericine) biosynthetic pathway; MIAs are used in cancer treatment
CC       and other medical applications (PubMed:31009114). Cytochrome P450
CC       catalyzing the hydroxylation of (+)-vincadifformine to (+)-
CC       minovincinine (PubMed:31009114). {ECO:0000269|PubMed:31009114}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(+)-vincadifformine + O2 + reduced [NADPH--hemoprotein
CC         reductase] = (+)-minovincinine + H(+) + H2O + oxidized [NADPH--
CC         hemoprotein reductase]; Xref=Rhea:RHEA:61040, Rhea:RHEA-COMP:11964,
CC         Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:142830, ChEBI:CHEBI:144371;
CC         Evidence={ECO:0000269|PubMed:31009114};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61041;
CC         Evidence={ECO:0000269|PubMed:31009114};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:Q96242};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.6 uM for (+)-vincadifformine (at pH 7.5 and 30 degrees Celsius)
CC         {ECO:0000269|PubMed:31009114};
CC         Vmax=20 nmol/min/ug enzyme with (+)-vincadifformine as substrate (at
CC         pH 7.5 and 30 degrees Celsius) {ECO:0000269|PubMed:31009114};
CC   -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:31009114}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:I1TEM1}; Single-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Accumulates progressively in roots.
CC       {ECO:0000269|PubMed:31009114}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; MK050464; QCZ35502.1; -; mRNA.
DR   AlphaFoldDB; P0DO22; -.
DR   SMR; P0DO22; -.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IDA:UniProtKB.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0035835; P:indole alkaloid biosynthetic process; IDA:UniProtKB.
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; Endoplasmic reticulum; Heme; Iron; Membrane;
KW   Metal-binding; Monooxygenase; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..506
FT                   /note="(+)-vincadifformine 19-hydroxylase"
FT                   /id="PRO_0000448556"
FT   TOPO_DOM        1..4
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        5..25
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        26..506
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   BINDING         450
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   506 AA;  57503 MW;  20E0087686E0EEA7 CRC64;
     MELDECSPSI FIISFIFIAI SIAILRRIRP KKTKALPPGP WKLPLIGNLH QFISRDSLPY
     KILRDLAQKH GPLMHLQLGE VSAVVASSPE MAKVITRTKD LEFADKPAIR AIRIVTYDYL
     DIAFNSYGKY WREMRKIFVQ ELLTPKRVRS FWSAREDVFS NLVKTINSAN GKSINLTKLI
     SSTTNSIINR VALGNVPYER EIFMELIKQL LTAAGGFKLV DLFPSYKIIH VLEGTERKLW
     KILGKIDKIL DKVIDEHREN LLRTGKGSGE NGQEDIVDIL LKIEDGGELD HDIPFGNNNI
     KALLFDIISG GSDTSSTTID WAMSEMMKNP QVMSKAQKEI REAFNGKKKI DENDVQNLKY
     LKSVIQETLR LHPPAAFLMR QCREECEIGG YHIPVGTKVF INIWAMGRDP EHWPNPESFI
     PERFENIPYD FTGSEHQLAT FPFGSGRRIC PGISFGLANV ELSLALLLYH FNWQLPDSST
     DLDMTEAIGI AARRKYDLHL IPTSYM