MCE_TALPI
ID MCE_TALPI Reviewed; 603 AA.
AC A0A1S7IUL2;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Multicopper oxidase MCE {ECO:0000303|PubMed:29468784};
DE EC=1.-.-.- {ECO:0000269|PubMed:29468784};
DE AltName: Full=Dinapinone A biosynthesis cluster protein MCE {ECO:0000303|PubMed:29468784};
DE AltName: Full=Monapinone coupling enzyme {ECO:0000303|PubMed:29468784};
DE Short=MCE {ECO:0000303|PubMed:29468784};
DE Flags: Precursor;
GN Name=MCE {ECO:0000303|PubMed:29468784};
GN Synonyms=ORF6 {ECO:0000303|PubMed:29468784};
OS Talaromyces pinophilus (Penicillium pinophilum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC Talaromyces sect. Talaromyces.
OX NCBI_TaxID=128442;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBSTRATE SPECIFICITY,
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=FKI-3864;
RX PubMed=29468784; DOI=10.1002/anie.201800415;
RA Kawaguchi M., Ohshiro T., Toyoda M., Ohte S., Inokoshi J., Fujii I.,
RA Tomoda H.;
RT "Discovery of a fungal multicopper oxidase that catalyzes the
RT regioselective coupling of a tricyclic naphthopyranone to produce
RT atropisomers.";
RL Angew. Chem. Int. Ed. 57:5115-5119(2018).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=21559025; DOI=10.1038/ja.2011.32;
RA Ohte S., Matsuda D., Uchida R., Nonaka K., Masuma R., Omura S., Tomoda H.;
RT "Dinapinones, novel inhibitors of triacylglycerol synthesis in mammalian
RT cells, produced by Penicillium pinophilum FKI-3864.";
RL J. Antibiot. 64:489-494(2011).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=30108268; DOI=10.1038/s41598-018-30679-0;
RA Kobayashi K., Ohte S., Ohshiro T., Ugaki N., Tomoda H.;
RT "A mixture of atropisomers enhances neutral lipid degradation in mammalian
RT cells with autophagy induction.";
RL Sci. Rep. 8:12099-12099(2018).
CC -!- FUNCTION: Multicopper oxidase; part of the gene cluster that mediates
CC the biosynthesis of dinapinones DPA1 (or (M)-DPA) and DPA2 (or (P)-
CC DPA), biaryl dihydronaphthopyranones that act in concert as inhibitors
CC of triacylglycerol accumulation in mammalian cells (PubMed:29468784).
CC The first step in the pathway corresponds to the biosynthesis of
CC dihydroxy-decanoyl-CoA by the fungal type I fatty acid synthase (formed
CC by ORF4 and ORF5) (Probable). The cluster-specific polyketide synthase
CC (ORF7) then accepts and extends dihydroxy-decanoyl-CoA with 6 malonyl-
CC CoA moieties and cyclizes the molecule to produce a putative
CC polyhydroxynaphthopyranone intermediate, which is further methylated by
CC the cluster-specific methyltransferase (ORF1) at 7-OH to produce
CC monapinone A (MPA) (Probable). MCE catalyzes the regioselective biaryl
CC coupling of monapinone A (MPA) at the 8,8'-positions to afford dimeric
CC atropisomers DPA1 and DPA2 in a ratio of approximately 1:2.5
CC (PubMed:29468784). Monapinone E (MPE) appears also to be a substrate
CC for MCE and provides the atropisomers dinapinones DPE1 (or (M)-DPE) and
CC DPE2 (or (P)-DPE) (PubMed:29468784). {ECO:0000269|PubMed:29468784,
CC ECO:0000305|PubMed:29468784}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 monapinone A + O2 = 2 dinapinone A + 2 H2O;
CC Xref=Rhea:RHEA:62812, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:145922, ChEBI:CHEBI:145923;
CC Evidence={ECO:0000269|PubMed:29468784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62813;
CC Evidence={ECO:0000269|PubMed:29468784};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 monapinone E + O2 = 2 dinapinone E + 2 H2O;
CC Xref=Rhea:RHEA:62816, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:146004, ChEBI:CHEBI:146005;
CC Evidence={ECO:0000269|PubMed:29468784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62817;
CC Evidence={ECO:0000269|PubMed:29468784};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=72.7 uM for monapinone A {ECO:0000269|PubMed:29468784};
CC KM=85.0 uM for monapinone E {ECO:0000269|PubMed:29468784};
CC Vmax=1.21 umol/min/mg enzyme toward monapinone A
CC {ECO:0000269|PubMed:29468784};
CC Vmax=3.33 umol/min/mg enzyme toward monapinone E
CC {ECO:0000269|PubMed:29468784};
CC pH dependence:
CC Optimum pH is 4.0. {ECO:0000269|PubMed:29468784};
CC Temperature dependence:
CC Optimum temperature is 50 degrees Celsius.
CC {ECO:0000269|PubMed:29468784};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:29468784}.
CC -!- BIOTECHNOLOGY: A mixture of dinapinones A1 and A2 at a ratio of 1:1 or
CC 1:2 leads to inhibition of triacylglycerol accumulation in mammalian
CC cells, suggesting that these compounds might be interresting to treat
CC obesity (PubMed:21559025). This inhibitory activity is mostly provided
CC by dinapinone A2 but is potentiated by dinapinone A1 (PubMed:21559025,
CC PubMed:30108268). Dinapinones do not affect diacylglycerol
CC acyltransferase (DGAT) activity but enhance neutral lipid degradation
CC together with induction of autophagy (PubMed:30108268).
CC {ECO:0000269|PubMed:21559025, ECO:0000269|PubMed:30108268}.
CC -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
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DR EMBL; LC030116; BAW99827.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1S7IUL2; -.
DR SMR; A0A1S7IUL2; -.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.420; -; 3.
DR InterPro; IPR001117; Cu-oxidase.
DR InterPro; IPR011706; Cu-oxidase_C.
DR InterPro; IPR045087; Cu-oxidase_fam.
DR InterPro; IPR011707; Cu-oxidase_N.
DR InterPro; IPR033138; Cu_oxidase_CS.
DR InterPro; IPR002355; Cu_oxidase_Cu_BS.
DR InterPro; IPR008972; Cupredoxin.
DR PANTHER; PTHR11709; PTHR11709; 1.
DR Pfam; PF00394; Cu-oxidase; 1.
DR Pfam; PF07731; Cu-oxidase_2; 1.
DR Pfam; PF07732; Cu-oxidase_3; 1.
DR SUPFAM; SSF49503; SSF49503; 3.
DR PROSITE; PS00079; MULTICOPPER_OXIDASE1; 2.
DR PROSITE; PS00080; MULTICOPPER_OXIDASE2; 1.
PE 1: Evidence at protein level;
KW Copper; Glycoprotein; Metal-binding; Oxidoreductase; Repeat; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..603
FT /note="Multicopper oxidase MCE"
FT /id="PRO_5012503969"
FT DOMAIN 30..144
FT /note="Plastocyanin-like 1"
FT /evidence="ECO:0000255"
FT DOMAIN 173..353
FT /note="Plastocyanin-like 2"
FT /evidence="ECO:0000255"
FT DOMAIN 450..581
FT /note="Plastocyanin-like 3"
FT /evidence="ECO:0000255"
FT BINDING 79
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 81
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 123
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 125
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 495
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 394
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 512
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 595
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 603 AA; 67271 MW; 2B38713B058C5C6D CRC64;
MNTFICSALI CLSWLPGFIQ ARVLTKKLTI TYAKGAPDGI ERDMIFINGQ FPGPDLIFDE
GDDVVINVVN DMPFNTTVHW HGLLMQGTPW SDGVPGLTQK PIEPGESFVY RFKAEPAGTY
WYHSHSRATL LDGLYGALWI RPKENVPMPF TMISNSSDDL SAMERAAKNP QLLIVSDWSN
FTSWQYIQGL VASELDIFCV DSILLNGKGS SYCPGQRLLE SELSAYMNYA FGGANITDKG
CFPFVESTEG PYLPGNQSAI PDHMWKDCVL GNGSNETIYV DPEEKWVSLN IVMASTMKSV
VFSIDEHDLW LYELDGQLIE PIKYQWVTML PSKRYSVLVK LNKTPGDYTI RLPDQGFSQI
ISGFATFSYK GGQDIGQTTP WVTYGGQNAS DQGNGSGLTD LLPAPFPALR PRNTSDVFFV
YNLYRWNAAY TWSLTGAAAM PVDDWAYQPL LYNPNSTAAH DKSLVIRTKY GQWVDLILQV
GSKPDERQEI NHVIHKHSSR AWQVGSGSGI WNYTSVDEAA TLHPELFNFE NPPYMDVFAT
SFEGPSWLIM RYQVTNPGPW LLHCHSEIHL AGGMAGVIMD GVDRWPTIPP AYAPNATGHY
PLV
