ID   ISY1_NEPCA              Reviewed;         388 AA.
AC   A0A221J5W8;
DT   17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2017, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=(S)-8-oxocitronellyl enol synthase ISY1 {ECO:0000305};
DE            EC=1.3.1.122 {ECO:0000269|PubMed:29091815};
DE   AltName: Full=Iridoid synthase 1 {ECO:0000303|PubMed:29091815};
DE            Short=NcISY1 {ECO:0000303|PubMed:29091815};
GN   Name=ISY1 {ECO:0000303|PubMed:29091815};
OS   Nepeta cataria (Catnip).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Mentheae; Nepetinae;
OC   Nepeta.
OX   NCBI_TaxID=39347 {ECO:0000312|EMBL:ASM62109.1};
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND ACTIVE SITES.
RX   PubMed=29091815; DOI=10.1016/j.phytochem.2017.10.004;
RA   Sherden N.H., Lichman B., Caputi L., Zhao D., Kamileen M.O., Buell C.R.,
RA   O'Connor S.E.;
RT   "Identification of iridoid synthases from Nepeta species: Iridoid
RT   cyclization does not determine nepetalactone stereochemistry.";
RL   Phytochemistry 145:48-56(2018).
CC   -!- FUNCTION: Iridoid synthase that catalyzes the first step in generation
CC       of the iridoid ring scaffold using the linear monoterpene (6E)-8-
CC       oxogeranial as substrate (PubMed:29091815). Iridoids comprise a large
CC       family of distinctive bicyclic monoterpenes that possess a wide range
CC       of pharmacological activities, including anticancer, anti-inflammatory,
CC       antifungal and antibacterial activities (Probable). Catalyzes the
CC       conversion of the linear monoterpene (6E)-8-oxogeranial to (S)-8-
CC       oxocitronellyl enol, a precursor of nepetalactones, which are
CC       metabolites that are both insect-repellent and have euphoric effect in
CC       cats (PubMed:29091815). {ECO:0000269|PubMed:29091815, ECO:0000305}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-8-oxocitronellyl enol + NADP(+) = (6E)-8-oxogeranial +
CC         H(+) + NADPH; Xref=Rhea:RHEA:62592, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:64239,
CC         ChEBI:CHEBI:144481; EC=1.3.1.122;
CC         Evidence={ECO:0000269|PubMed:29091815};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:62594;
CC         Evidence={ECO:0000269|PubMed:29091815};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-8-oxocitronellyl enol + NAD(+) = (6E)-8-oxogeranial + H(+)
CC         + NADH; Xref=Rhea:RHEA:62596, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945, ChEBI:CHEBI:64239, ChEBI:CHEBI:144481;
CC         EC=1.3.1.122; Evidence={ECO:0000250|UniProtKB:K7WDL7};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:62598;
CC         Evidence={ECO:0000250|UniProtKB:K7WDL7};
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; KY882233; ASM62109.1; -; mRNA.
DR   AlphaFoldDB; A0A221J5W8; -.
DR   SMR; A0A221J5W8; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   1: Evidence at protein level;
KW   NAD; NADP; Oxidoreductase.
FT   CHAIN           1..388
FT                   /note="(S)-8-oxocitronellyl enol synthase ISY1"
FT                   /id="PRO_0000449836"
FT   ACT_SITE        147
FT                   /evidence="ECO:0000305|PubMed:29091815"
FT   ACT_SITE        178
FT                   /evidence="ECO:0000305|PubMed:29091815"
FT   BINDING         35..37
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         63..64
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         81..82
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         105..106
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         143
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         178
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         205
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9STX2"
FT   BINDING         212..214
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
SQ   SEQUENCE   388 AA;  43916 MW;  F05B60368E674893 CRC64;
     MSWWWAGAIG AAKKKIDEDE APRNYESVAL IVGVTGIVGN SLAEILPLSD TPGGPWKVYG
     VARRPRPSWN EDHPITYISC DVLDSVDVEA KLSPLTDVTH IFYATWTKRS TEKENCEANG
     KMLKNVLNAM IPNCPNLKHI CLQTGRKHYL GAFEDLKSKC HDPPLTEDLP RLDSQNYYYT
     QEDILFEEVQ KKEGLTWSVH RPGTIFGFSP YSMMNLVGTL CVYAAICKHE GAVLRFPGCK
     GAWDGYSDCS DADLIAEHQI WAAVDPYAKN EAFNVSNGDV FKWKHFWKVL AEQFGVECGE
     YEEGQQVKLQ DLMKDKGPVW DKIVRENGLS TTKLEDVGNW WFSDIVLGNE CWLDTMNKSK
     EHGFLGFRNS KNSFISWIDK VKAFKIVP