ID   NEPS2_NEPRA             Reviewed;         268 AA.
AC   A0A3Q8GYY4;
DT   17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT   10-APR-2019, sequence version 1.
DT   03-AUG-2022, entry version 11.
DE   RecName: Full=(+)-cis,trans-nepetalactol synthase NEPS2 {ECO:0000305};
DE            EC=5.5.1.34 {ECO:0000269|PubMed:30531909, ECO:0000269|PubMed:30664302};
DE   AltName: Full=Nepetalactol-related short-chain reductase 2 {ECO:0000303|PubMed:30531909};
DE            Short=NmNEPS2 {ECO:0000303|PubMed:30531909};
GN   Name=NEPS2 {ECO:0000303|PubMed:30531909};
OS   Nepeta racemosa (Catmint) (Raceme 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=54731;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=30531909; DOI=10.1038/s41589-018-0185-2;
RA   Lichman B.R., Kamileen M.O., Titchiner G.R., Saalbach G., Stevenson C.E.M.,
RA   Lawson D.M., O'Connor S.E.;
RT   "Uncoupled activation and cyclization in catmint reductive terpenoid
RT   biosynthesis.";
RL   Nat. Chem. Biol. 15:71-79(2019).
RN   [2]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=30664302; DOI=10.1002/chem.201805412;
RA   Lichman B.R., O'Connor S.E., Kries H.;
RT   "Biocatalytic strategies towards [4+2] cycloadditions.";
RL   Chemistry 25:6864-6877(2019).
CC   -!- FUNCTION: Functions as a non-oxidoreductive cyclase to promote the
CC       formation of cis-trans-nepetalactol (PubMed:30531909, PubMed:30664302).
CC       Cis-trans-nepetalactol is then oxidized by NEPS1 into cis-trans-
CC       nepetalactone, which belongs to a family of metabolites that are both
CC       insect-repellent and have euphoric effect in cats (PubMed:30531909,
CC       PubMed:30664302). Binds NAD(+) as classical short-chain
CC       dehydrogenase/reductase (SDR), but does not utilize it for its redox-
CC       neutral cyclase activity (By similarity).
CC       {ECO:0000250|UniProtKB:A0A3Q8GLE8, ECO:0000269|PubMed:30531909,
CC       ECO:0000269|PubMed:30664302}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-8-oxocitronellyl enol = cis-trans-nepetalactol;
CC         Xref=Rhea:RHEA:61416, ChEBI:CHEBI:71494, ChEBI:CHEBI:144481;
CC         EC=5.5.1.34; Evidence={ECO:0000269|PubMed:30531909,
CC         ECO:0000269|PubMed:30664302};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61417;
CC         Evidence={ECO:0000269|PubMed:30531909, ECO:0000269|PubMed:30664302};
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; MG677125; AXF35972.1; -; mRNA.
DR   AlphaFoldDB; A0A3Q8GYY4; -.
DR   SMR; A0A3Q8GYY4; -.
DR   KEGG; ag:AXF35972; -.
DR   BRENDA; 5.5.1.34; 12895.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   PRINTS; PR00081; GDHRDH.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
PE   1: Evidence at protein level;
KW   Isomerase; NAD.
FT   CHAIN           1..268
FT                   /note="(+)-cis,trans-nepetalactol synthase NEPS2"
FT                   /id="PRO_0000449832"
FT   BINDING         16..22
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:A0A3Q8GLE8"
FT   BINDING         41..43
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:A0A3Q8GLE8"
FT   BINDING         65..66
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:A0A3Q8GLE8"
FT   BINDING         92
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:A0A3Q8GLE8"
FT   BINDING         163..167
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:A0A3Q8GLE8"
FT   BINDING         196..200
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:A0A3Q8GLE8"
SQ   SEQUENCE   268 AA;  28024 MW;  9BC4F8DD7AA53B21 CRC64;
     MGNKKTLEGK VAIVTGGASG IGETAARVFA NLGARAVVIA DIQSELGREV AESIGAKRCS
     YVQCDIGDEE QVKSMVEWTA TTYGALDVMF CNAGIMSKAE SAQTVLELDM SKFDEVMRVN
     TRGTSACVKQ AARKMVELGT KGGAIVCTSS PLASRGGYID TDYVMSKHAV MGLVRSASMQ
     LGAHGIRVNS VSPMAVLTPL TRRMGLATPA DVENAFGRFT SLKGVALTAE HVAEAAAFLA
     SDEAAFITGH DLMVDGGLLC LPFFAPTS