RETO_ESCCA
ID RETO_ESCCA Reviewed; 538 AA.
AC P30986;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Reticuline oxidase;
DE EC=1.21.3.3;
DE AltName: Full=Berberine bridge-forming enzyme;
DE Short=BBE;
DE AltName: Full=Tetrahydroprotoberberine synthase;
DE Flags: Precursor;
GN Name=BBE1;
OS Eschscholzia californica (California poppy).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Ranunculales; Papaveraceae;
OC Eschscholzioideae; Eschscholzia.
OX NCBI_TaxID=3467;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 24-47; 81-88; 238-243;
RP 351-354 AND 473-483.
RX PubMed=1946465; DOI=10.1073/pnas.88.22.9969;
RA Dittrich H., Kutchan T.M.;
RT "Molecular cloning, expression, and induction of berberine bridge enzyme,
RT an enzyme essential to the formation of benzophenanthridine alkaloids in
RT the response of plants to pathogenic attack.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:9969-9973(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9484487; DOI=10.1023/a:1005917808232;
RA Hauschild K., Pauli H.H., Kutchan T.M.;
RT "Isolation and analysis of a gene bbe1 encoding the berberine bridge enzyme
RT from the California poppy Eschscholzia californica.";
RL Plant Mol. Biol. 36:473-478(1998).
RN [3]
RP PROTEIN SEQUENCE OF 24-28; 101-127 AND 159-185, COFACTOR, AND GLYCOSYLATION
RP AT ASN-38.
RX PubMed=16728404; DOI=10.1074/jbc.m603267200;
RA Winkler A., Hartner F., Kutchan T.M., Glieder A., Macheroux P.;
RT "Biochemical evidence that berberine bridge enzyme belongs to a novel
RT family of flavoproteins containing a bi-covalently attached FAD cofactor.";
RL J. Biol. Chem. 281:21276-21285(2006).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=24240298; DOI=10.1007/bf00391333;
RA Amann M., Wanner G., Zenk M.H.;
RT "Intracellular compartmentation of two enzymes of berberine biosynthesis in
RT plant cell cultures.";
RL Planta 167:310-320(1986).
RN [5] {ECO:0007744|PDB:3FW7, ECO:0007744|PDB:3FW8, ECO:0007744|PDB:3FW9, ECO:0007744|PDB:3FWA}
RP X-RAY CRYSTALLOGRAPHY (1.49 ANGSTROMS) OF 26-520 IN COMPLEX WITH FAD,
RP DISULFIDE BOND, GLYCOSYLATION AT ASN-471, AND COFACTOR.
RX PubMed=19457868; DOI=10.1074/jbc.m109.015727;
RA Winkler A., Motz K., Riedl S., Puhl M., Macheroux P., Gruber K.;
RT "Structural and mechanistic studies reveal the functional role of
RT bicovalent flavinylation in berberine bridge enzyme.";
RL J. Biol. Chem. 284:19993-20001(2009).
CC -!- FUNCTION: Essential to the formation of benzophenanthridine alkaloids
CC in the response of plants to pathogenic attack. Catalyzes the
CC stereospecific conversion of the N-methyl moiety of (S)-reticuline into
CC the berberine bridge carbon of (S)-scoulerine.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-reticuline + O2 = (S)-scoulerine + H(+) + H2O2;
CC Xref=Rhea:RHEA:19885, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:17129, ChEBI:CHEBI:57873; EC=1.21.3.3;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:16728404, ECO:0000269|PubMed:19457868};
CC Note=Binds 1 FAD per subunit in a bicovalent manner.
CC {ECO:0000269|PubMed:16728404, ECO:0000269|PubMed:19457868};
CC -!- COFACTOR:
CC Name=a metal cation; Xref=ChEBI:CHEBI:25213;
CC -!- PATHWAY: Alkaloid biosynthesis; (S)-scoulerine biosynthesis; (S)-
CC scoulerine from (S)-reticuline: step 1/1.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle
CC {ECO:0000269|PubMed:24240298}. Note=Found in cytoplasmic vesicles that
CC are highly specific and unique compartments serving only alkaloid
CC biosynthesis. The protein composition of these vesicles reveals the
CC presence of only about 20 separable proteins.
CC {ECO:0000269|PubMed:24240298}.
CC -!- PTM: The FAD cofactor is bound via a bicovalent 6-S-cysteinyl, 8alpha-
CC N1-histidyl FAD linkage. {ECO:0000269|PubMed:16728404,
CC ECO:0000269|PubMed:19457868}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; S65550; AAB20352.1; -; mRNA.
DR EMBL; AF005655; AAC39358.1; -; Genomic_DNA.
DR PIR; A41533; A41533.
DR PDB; 3D2D; X-ray; 2.80 A; A=1-21, A=24-538.
DR PDB; 3D2H; X-ray; 1.65 A; A=1-21, A=24-538.
DR PDB; 3D2J; X-ray; 2.05 A; A=1-21, A=24-538.
DR PDB; 3FW7; X-ray; 1.82 A; A=24-520.
DR PDB; 3FW8; X-ray; 1.50 A; A=26-520.
DR PDB; 3FW9; X-ray; 1.49 A; A=26-520.
DR PDB; 3FWA; X-ray; 1.50 A; A=26-522.
DR PDB; 3GSY; X-ray; 1.63 A; A=24-538.
DR PDB; 4EC3; X-ray; 2.65 A; A=24-538.
DR PDB; 4PZF; X-ray; 2.20 A; A/B/C/D=1-538.
DR PDBsum; 3D2D; -.
DR PDBsum; 3D2H; -.
DR PDBsum; 3D2J; -.
DR PDBsum; 3FW7; -.
DR PDBsum; 3FW8; -.
DR PDBsum; 3FW9; -.
DR PDBsum; 3FWA; -.
DR PDBsum; 3GSY; -.
DR PDBsum; 4EC3; -.
DR PDBsum; 4PZF; -.
DR AlphaFoldDB; P30986; -.
DR SMR; P30986; -.
DR CAZy; AA7; Auxiliary Activities 7.
DR iPTMnet; P30986; -.
DR KEGG; ag:AAC39358; -.
DR BioCyc; MetaCyc:MON-12338; -.
DR BRENDA; 1.21.3.3; 2173.
DR UniPathway; UPA00319; UER00450.
DR EvolutionaryTrace; P30986; -.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0050468; F:reticuline oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR InterPro; IPR006093; Oxy_OxRdtase_FAD_BS.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
DR PROSITE; PS00862; OX2_COVAL_FAD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alkaloid metabolism; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; FAD; Flavoprotein; Glycoprotein;
KW Oxidoreductase; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:1946465"
FT CHAIN 24..538
FT /note="Reticuline oxidase"
FT /id="PRO_0000020425"
FT DOMAIN 67..241
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16728404,
FT ECO:0000269|PubMed:19457868"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 471
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19457868"
FT DISULFID 30..89
FT /evidence="ECO:0000269|PubMed:19457868"
FT CROSSLNK 104..166
FT /note="6-(S-cysteinyl)-8alpha-(pros-histidyl)-FAD (His-
FT Cys)"
FT /evidence="ECO:0000269|PubMed:16728404,
FT ECO:0000269|PubMed:19457868"
FT HELIX 27..33
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:3D2D"
FT HELIX 49..56
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:3D2J"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 80..91
FT /evidence="ECO:0007829|PDB:3FW9"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:3FWA"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:3FW9"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:3D2H"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:3FW9"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 145..155
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 171..176
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 190..193
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 209..212
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 214..220
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:4PZF"
FT STRAND 230..237
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 243..254
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 256..272
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 277..286
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 289..300
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 302..312
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 328..335
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 341..345
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 355..362
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 369..381
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 385..391
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 394..397
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:3FW9"
FT STRAND 414..422
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 424..429
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 430..444
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 457..459
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 462..464
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 472..476
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 478..490
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 491..493
FT /evidence="ECO:0007829|PDB:3FW9"
FT HELIX 494..504
FT /evidence="ECO:0007829|PDB:3FW9"
SQ SEQUENCE 538 AA; 59958 MW; 1A505F86A06CDB24 CRC64;
MENKTPIFFS LSIFLSLLNC ALGGNDLLSC LTFNGVRNHT VFSADSDSDF NRFLHLSIQN
PLFQNSLISK PSAIILPGSK EELSNTIRCI RKGSWTIRLR SGGHSYEGLS YTSDTPFILI
DLMNLNRVSI DLESETAWVE SGSTLGELYY AITESSSKLG FTAGWCPTVG TGGHISGGGF
GMMSRKYGLA ADNVVDAILI DANGAILDRQ AMGEDVFWAI RGGGGGVWGA IYAWKIKLLP
VPEKVTVFRV TKNVAIDEAT SLLHKWQFVA EELEEDFTLS VLGGADEKQV WLTMLGFHFG
LKTVAKSTFD LLFPELGLVE EDYLEMSWGE SFAYLAGLET VSQLNNRFLK FDERAFKTKV
DLTKEPLPSK AFYGLLERLS KEPNGFIALN GFGGQMSKIS SDFTPFPHRS GTRLMVEYIV
AWNQSEQKKK TEFLDWLEKV YEFMKPFVSK NPRLGYVNHI DLDLGGIDWG NKTVVNNAIE
ISRSWGESYF LSNYERLIRA KTLIDPNNVF NHPQSIPPMA NFDYLEKTLG SDGGEVVI
