NEPS3_NEPRA
ID NEPS3_NEPRA Reviewed; 270 AA.
AC A0A3Q8GLE8; A0A4P1LYE8;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=(+)-cis,cis-nepetalactol synthase NEPS3 {ECO:0000305};
DE EC=5.5.1.35 {ECO:0000269|PubMed:30531909, ECO:0000269|PubMed:30664302};
DE AltName: Full=Nepetalactol-related short-chain reductase 3 {ECO:0000303|PubMed:30531909};
DE Short=NmNEPS3 {ECO:0000303|PubMed:30531909};
GN Name=NEPS3 {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], X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) IN
RP COMPLEX WITH NAD, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF
RP ASN-150; SER-154; LYS-169 AND MET-196.
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-cis-nepetalactol (PubMed:30531909, PubMed:30664302).
CC Cis-cis-nepetalactol is then oxidized by NEPS1 into cis-cis-
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 (PubMed:30531909, PubMed:30664302).
CC {ECO:0000269|PubMed:30531909, ECO:0000269|PubMed:30664302}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-8-oxocitronellyl enol = cis-cis-nepetalactol;
CC Xref=Rhea:RHEA:61420, ChEBI:CHEBI:144481, ChEBI:CHEBI:144485;
CC EC=5.5.1.35; Evidence={ECO:0000269|PubMed:30531909,
CC ECO:0000269|PubMed:30664302};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61421;
CC Evidence={ECO:0000269|PubMed:30531909, ECO:0000269|PubMed:30664302};
CC -!- SUBUNIT: Forms homotetramers. {ECO:0000269|PubMed:30531909}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; MG677126; AXF35973.1; -; mRNA.
DR PDB; 6F9Q; X-ray; 1.40 A; A/B/C/D=1-270.
DR PDBsum; 6F9Q; -.
DR AlphaFoldDB; A0A3Q8GLE8; -.
DR SMR; A0A3Q8GLE8; -.
DR KEGG; ag:AXF35973; -.
DR BRENDA; 5.5.1.35; 12895.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase; NAD.
FT CHAIN 1..270
FT /note="(+)-cis,cis-nepetalactol synthase NEPS3"
FT /id="PRO_0000449833"
FT BINDING 21..27
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:30531909,
FT ECO:0007744|PDB:6F9Q"
FT BINDING 46..48
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:30531909,
FT ECO:0007744|PDB:6F9Q"
FT BINDING 70..71
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:30531909,
FT ECO:0007744|PDB:6F9Q"
FT BINDING 97
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:30531909,
FT ECO:0007744|PDB:6F9Q"
FT BINDING 165..169
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:30531909,
FT ECO:0007744|PDB:6F9Q"
FT BINDING 198..202
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:30531909,
FT ECO:0007744|PDB:6F9Q"
FT MUTAGEN 150
FT /note="N->T: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:30531909"
FT MUTAGEN 154
FT /note="S->L: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:30531909"
FT MUTAGEN 169
FT /note="K->M: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:30531909"
FT MUTAGEN 196
FT /note="M->S: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:30531909"
FT TURN 11..14
FT /evidence="ECO:0007829|PDB:6F9Q"
FT STRAND 16..20
FT /evidence="ECO:0007829|PDB:6F9Q"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:6F9Q"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 49..59
FT /evidence="ECO:0007829|PDB:6F9Q"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:6F9Q"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 74..88
FT /evidence="ECO:0007829|PDB:6F9Q"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 113..123
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 125..141
FT /evidence="ECO:0007829|PDB:6F9Q"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 163..183
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:6F9Q"
FT STRAND 188..195
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 201..204
FT /evidence="ECO:0007829|PDB:6F9Q"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 211..217
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 231..242
FT /evidence="ECO:0007829|PDB:6F9Q"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:6F9Q"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:6F9Q"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:6F9Q"
SQ SEQUENCE 270 AA; 28179 MW; 555F2DC42A6D9209 CRC64;
MANNSVMMKK KLEGKVAIVT GGASGIGEAT ARLFVKYGAR AVVIADIQSE LGRSVAESIG
KERCSFVQCD VADEEQVKSM IEWTATTYGG LDVMFSNAGV LNSAAQTVKD LDLPLFDKVM
RVNTRGAAVC VKQAARKMVE LGRGGSIICN AGSSAVRGAH GVTDYVMSKH AVIGLVRSAS
MQLGAHSIRV NSVSPMAVAT PLTRNQGIST PDDVQKFLMP FISLKGVPPT AEQVAEAAAF
LGSDEAAFVT GHDLPVDGGV LCMPFLLGSA
