ID   ISY2_NEPCA              Reviewed;         397 AA.
AC   A0A221J5X1;
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 ISY2 {ECO:0000305};
DE            EC=1.3.1.122 {ECO:0000269|PubMed:29091815};
DE   AltName: Full=Iridoid synthase 2 {ECO:0000303|PubMed:29091815};
DE            Short=NcISY2 {ECO:0000303|PubMed:29091815};
GN   Name=ISY2 {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;
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; KY882234; ASM62110.1; -; mRNA.
DR   AlphaFoldDB; A0A221J5X1; -.
DR   SMR; A0A221J5X1; -.
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..397
FT                   /note="(S)-8-oxocitronellyl enol synthase ISY2"
FT                   /id="PRO_0000449837"
FT   ACT_SITE        180
FT                   /evidence="ECO:0000305|PubMed:29091815"
FT   BINDING         36..38
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         64..65
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         82..83
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         106..107
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         144
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         180
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
FT   BINDING         207
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9STX2"
FT   BINDING         214..216
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:K7WDL7"
SQ   SEQUENCE   397 AA;  45107 MW;  E49BA9CD46F6537D CRC64;
     MSMNWWRDGA AKKRMDESSA VKLQQQQCVA LIVGVTGLVG NSLAEMLPLS DTPGGPWKVY
     GVARRPRPSW NEDHPINYIS CDVSNTAEVE AKLPPLSDVT HIFYATWTSR SSEEENCEAN
     GKMLKNVLDT MIPNCPNLKH ICLQTGRFHY VASVVDWKIN GSHDTPLTED LPRLNTNNFY
     YTQEDILLEE VKRKEGLTWS VHRPGTIFGF SPYSMMNLVG TLCVYAAICK QEGAVLRFPG
     CKGAWDGYSD CADADLIAEH YIWAALDPHA KNQSFNVSNG DVFKWKHLWK VLAEQFGVEC
     GGYEYEEGQQ VRLQDVMKDK GPVWDKIVRE NGLSNTKLED VGKWWFSDTI LWNECRLDSM
     NKSKEHGFLG FRNSKNCFLY WIHKLKAYKI VPSSTIS