T19H_CATRO
ID T19H_CATRO Reviewed; 507 AA.
AC F5BHA2;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Tabersonine/lochnericine 19-hydroxylase {ECO:0000303|PubMed:31009114};
DE EC=1.14.14.- {ECO:0000269|PubMed:21454651, ECO:0000269|PubMed:31009114};
DE AltName: Full=Cytochrome P450 71BJ1 {ECO:0000303|PubMed:21454651, ECO:0000303|PubMed:31009114};
GN Name=T19H {ECO:0000303|PubMed:31009114};
GN Synonyms=CYP71BJ1 {ECO:0000303|PubMed:21454651,
GN 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, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21454651; DOI=10.1074/jbc.m111.225383;
RA Giddings L.-A., Liscombe D.K., Hamilton J.P., Childs K.L., Dellapenna D.,
RA Buell C.R., O'Connor S.E.;
RT "A stereoselective hydroxylation step of alkaloid biosynthesis by a unique
RT cytochrome P450 in Catharanthus roseus.";
RL J. Biol. Chem. 286:16751-16757(2011).
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=29438577; DOI=10.1111/tpj.13868;
RA Carqueijeiro I., Duge de Bernonville T., Lanoue A., Dang T.-T.,
RA Teijaro C.N., Paetz C., Billet K., Mosquera A., Oudin A., Besseau S.,
RA Papon N., Glevarec G., Atehortua L., Clastre M., Giglioli-Guivarc'h N.,
RA Schneider B., St-Pierre B., Andrade R.B., O'Connor S.E., Courdavault V.;
RT "A BAHD acyltransferase catalyzing 19-O-acetylation of tabersonine
RT derivatives in roots of Catharanthus roseus enables combinatorial synthesis
RT of monoterpene indole alkaloids.";
RL Plant J. 94:469-484(2018).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 conversion of (-)-tabersonine to 19-hydroxytabersonine,
CC of lochnericine to horhammericine and of (-)-vincadifformine to (-)-
CC minovincinine (PubMed:31009114, PubMed:21454651).
CC {ECO:0000269|PubMed:21454651, ECO:0000269|PubMed:31009114}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(-)-tabersonine + O2 + reduced [NADPH--hemoprotein reductase]
CC = (-)-(R)-19-hydroxytabersonine + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:61044, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:57893,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:144372;
CC Evidence={ECO:0000269|PubMed:21454651, ECO:0000269|PubMed:31009114};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61045;
CC Evidence={ECO:0000269|PubMed:21454651, ECO:0000269|PubMed:31009114};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lochnericine + O2 + reduced [NADPH--hemoprotein reductase] =
CC H(+) + H2O + horhammericine + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:61048, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:144374,
CC ChEBI:CHEBI:144375; Evidence={ECO:0000269|PubMed:21454651,
CC ECO:0000269|PubMed:31009114};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61049;
CC Evidence={ECO:0000269|PubMed:21454651, 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:61052, 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:142771, ChEBI:CHEBI:144373;
CC Evidence={ECO:0000269|PubMed:31009114};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61053;
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=300 nM for tabersonine (at pH 7 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:21454651};
CC Vmax=5 umol/min/ug enzyme with tabersonine as substrate (at pH 7 and
CC 30 degrees Celsius) {ECO:0000269|PubMed:21454651};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:21454651,
CC ECO:0000269|PubMed:31009114}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:29438577}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Confined to roots. {ECO:0000269|PubMed:29438577}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; HQ901597; ADZ48681.1; -; mRNA.
DR AlphaFoldDB; F5BHA2; -.
DR SMR; F5BHA2; -.
DR KEGG; ag:ADZ48681; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
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:0016829; F:lyase activity; IEA:UniProtKB-KW.
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; Glycoprotein; Heme; Iron;
KW Lyase; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..507
FT /note="Tabersonine/lochnericine 19-hydroxylase"
FT /id="PRO_0000448557"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 447
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"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 507 AA; 57811 MW; B59E8E1E9F3DB84F CRC64;
MLSSLKDFFV LLLPFFIGIA FIYKLWNFTS KKNLPPSPRR LPIIGNLHQL SKFPQRSLRT
LSEKYGPVML LHFGSKPVLV ISSAEAAKEV MKINDVSFAD RPKWYAAGRV LYEFKDMTFS
PYGEYWRQAR SICVLQLLSN KRVQSFKGIR EEEIRAMLEK INQASNNSSI INGDEIFSTL
TNDIIGRSAF GRKFSEEESG SKLRKVLQDL PPLLGSFNVG DFIPWLSWVN YLNGFEKKLN
QVSKDCDQYL EQVIDDTRKR DEENGANNNG GNHGNFVSVL LHLQKEDVKG FPSEKGFLKA
IILDMIVGGT DTTHLLLHWV ITELLKNKHV MTKLQKEVRE IVGRKWEITD EDKEKMKYLH
AVIKEALRLH PSLPLLVPRV AREDINLMGY RVAKGTEVII NAWAIARDPS YWDEAEEFKP
ERFLSNNFDF KGLNFEYIPF GSGRRSCPGS SFAIPIVEHT VAHLMHKFNI ELPNGVSAED
FDPTDAVGLV SHDQNPLSFV ATPVTIF