ID   MER_ERYCB               Reviewed;         327 AA.
AC   E7C196;
DT   03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT   08-MAR-2011, sequence version 1.
DT   03-AUG-2022, entry version 34.
DE   RecName: Full=Methylecgonone reductase;
DE            Short=MecgoR;
DE            EC=1.1.1.334;
OS   Erythroxylum coca (Coca plant).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; fabids; Malpighiales; Erythroxylaceae; Erythroxylum.
OX   NCBI_TaxID=289672;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION,
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=22665766; DOI=10.1073/pnas.1200473109;
RA   Jirschitzka J., Schmidt G.W., Reichelt M., Schneider B., Gershenzon J.,
RA   D'Auria J.C.;
RT   "Plant tropane alkaloid biosynthesis evolved independently in the
RT   Solanaceae and Erythroxylaceae.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:10304-10309(2012).
CC   -!- FUNCTION: Catalyzes the stereospecific reduction of methylecgonone to
CC       methylecgonine, the penultimate step in cocaine biosynthesis. Can also
CC       use 6-hydroxytropinone, tropinone and nortropinone as substrates, but
CC       not 8-thiabicyclo[3.2.1]octan-3-one (TBON), cyclohexanone,
CC       cyclooctanone or N-methyl-4-piperidone. NADH can substitute for NADPH,
CC       but with a decreased activity. {ECO:0000269|PubMed:22665766}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ecgonine methyl ester + NADP(+) = ecgonone methyl ester + H(+)
CC         + NADPH; Xref=Rhea:RHEA:34211, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:59908, ChEBI:CHEBI:66941;
CC         EC=1.1.1.334; Evidence={ECO:0000269|PubMed:22665766};
CC   -!- ACTIVITY REGULATION: Strongly inhibited by Cu(2+) and Zn(2+) and to
CC       less than 30% by Co(2+) and Fe(2+). {ECO:0000269|PubMed:22665766}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=69.6 uM for ecgonone methyl ester {ECO:0000269|PubMed:22665766};
CC         KM=5.1 uM for NADPH {ECO:0000269|PubMed:22665766};
CC         KM=151.2 uM for ecgonine methyl ester {ECO:0000269|PubMed:22665766};
CC         KM=29.6 uM for NADP(+) {ECO:0000269|PubMed:22665766};
CC         Note=kcat is 0.24 sec(-1) for ecgonone methyl ester. kcat is 0.121
CC         sec(-1) for NADPH. kcat is 5.538 sec(-1) for ecgonine methyl ester.
CC         kcat is 5.238 sec(-1) for NADP(+).;
CC       pH dependence:
CC         Optimum pH is 6.8-9.8. {ECO:0000269|PubMed:22665766};
CC   -!- TISSUE SPECIFICITY: Expressed in young leaves. Detected in stems and
CC       flowers, but not in mature leaves or roots. Expressed in the palisade
CC       and spongy mesophyll tissue of leaves and sepals.
CC       {ECO:0000269|PubMed:22665766}.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR   EMBL; GU562618; ADK94763.1; -; mRNA.
DR   AlphaFoldDB; E7C196; -.
DR   SMR; E7C196; -.
DR   KEGG; ag:ADK94763; -.
DR   BRENDA; 1.1.1.334; 12906.
DR   SABIO-RK; E7C196; -.
DR   GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR   GO; GO:1901869; P:ecgonine methyl ester biosynthetic process; IDA:UniProtKB.
DR   GO; GO:1901868; P:ecgonine methyl ester catabolic process; IDA:UniProtKB.
DR   GO; GO:1901872; P:ecgonone methyl ester biosynthetic process; IDA:UniProtKB.
DR   GO; GO:1901871; P:ecgonone methyl ester catabolic process; IDA:UniProtKB.
DR   CDD; cd19124; AKR_AKR4A_4B; 1.
DR   Gene3D; 3.20.20.100; -; 1.
DR   InterPro; IPR020471; AKR.
DR   InterPro; IPR044497; AKR4A/B.
DR   InterPro; IPR018170; Aldo/ket_reductase_CS.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   PIRSF; PIRSF000097; AKR; 1.
DR   PRINTS; PR00069; ALDKETRDTASE.
DR   SUPFAM; SSF51430; SSF51430; 1.
DR   PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR   PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR   PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE   1: Evidence at protein level;
KW   Alkaloid metabolism; NADP; Oxidoreductase.
FT   CHAIN           1..327
FT                   /note="Methylecgonone reductase"
FT                   /id="PRO_0000421864"
FT   ACT_SITE        55
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   BINDING         118
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         220..279
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   327 AA;  36908 MW;  233B453C79CF4445 CRC64;
     MERQVPRVLL NSGHEMPVIG FGTAIDPLPE PEQLVSAILH AIEVGYRHFD TASAYMTEEP
     VGRAISEAMK RGLIKGREEL FVTSKLWCAD AHRDLIIPAL KETLKRLGLD YLDLYLIHFP
     VRLKKEAVSL EHEIDDFRFE DHELLPFDIK GTWEAMEECS RLGLTKSIGV SNYGTVKISQ
     LLQHATIPPA VNQVEMNVAW QQKKLREFCS KKGIHVTAWS PLAGIGAFWG STVVIESKTL
     KEIAAAKGKS VAQVALRWIQ DQGASCIVKS MNKDRMKQNL EIFGWKLSDE DGRKIEQIKQ
     SRLYPAKLFI NENSPYPSLE ALWDGDL