KABC_DIGSM
ID KABC_DIGSM Reviewed; 360 AA.
AC A0A4D6IA61;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Alpha-ketoglutarate dependent kainoid synthase {ECO:0000303|PubMed:30995339};
DE Short=Alpha-KG dependent kainoid synthase {ECO:0000303|PubMed:30995339};
DE EC=1.14.11.- {ECO:0000255|PROSITE-ProRule:PRU00805, ECO:0000269|PubMed:30995339};
DE AltName: Full=Kainic acid biosynthesis cluster protein C {ECO:0000303|PubMed:30995339};
DE Short=DsKabC {ECO:0000303|PubMed:30995339};
GN Name=kabC {ECO:0000303|PubMed:30995339};
OS Digenea simplex (Marine red alga) (Conferva simplex).
OC Eukaryota; Rhodophyta; Florideophyceae; Rhodymeniophycidae; Ceramiales;
OC Rhodomelaceae; Polysiphonioideae; Digenea.
OX NCBI_TaxID=945030;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP ACTIVITY REGULATION, AND BIOTECHNOLOGY.
RX PubMed=30995339; DOI=10.1002/anie.201902910;
RA Chekan J.R., McKinnie S.M.K., Moore M.L., Poplawski S.G., Michael T.P.,
RA Moore B.S.;
RT "Scalable biosynthesis of the seaweed neurochemical, kainic acid.";
RL Angew. Chem. Int. Ed. 58:8454-8457(2019).
RN [2]
RP REVIEW ON NEUROTOXIC ACTIVITY.
RX PubMed=10223631;
RX DOI=10.1002/(sici)1522-7189(199805/08)6:3/4<153::aid-nt16>3.0.co;2-1;
RA Hampson D.R., Manalo J.L.;
RT "The activation of glutamate receptors by kainic acid and domoic acid.";
RL Nat. Toxins 6:153-158(1998).
CC -!- FUNCTION: Iron/ascorbate-dependent oxidoreductase: part of the gene
CC cluster that mediates the biosynthesis of kainic acid (KA) and
CC derivatives, natural products with neurochemical activity acting as
CC ionotropic glutamate receptor (iGluR) agonists, thus being neurotoxins
CC (PubMed:30995339). Catalyzes the conversion of prekainic acid to kainic
CC acid and kainic acid lactone (PubMed:30995339).
CC {ECO:0000269|PubMed:30995339}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + prekainate = CO2 + H2O + kainate +
CC succinate; Xref=Rhea:RHEA:67480, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:156548, ChEBI:CHEBI:170011;
CC Evidence={ECO:0000269|PubMed:30995339};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67481;
CC Evidence={ECO:0000269|PubMed:30995339};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + H(+) + O2 + prekainate = CO2 + H2O + kainate
CC lactone + succinate; Xref=Rhea:RHEA:68224, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:170011,
CC ChEBI:CHEBI:177124; Evidence={ECO:0000269|PubMed:30995339};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68225;
CC Evidence={ECO:0000269|PubMed:30995339};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- ACTIVITY REGULATION: Inhibited by the iron chelator EDTA.
CC {ECO:0000269|PubMed:30995339}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30995339}.
CC -!- BIOTECHNOLOGY: Escherichia coli cells expressing Digenea simplex kabC
CC are successfully converting supplied synthetic prekainic acid into
CC kainic acid, thus providing a less expensive method to produce this
CC molecule for neuro-pharmacological applications.
CC {ECO:0000269|PubMed:30995339}.
CC -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; MK312630; QCC62383.1; -; Genomic_DNA.
DR SMR; A0A4D6IA61; -.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR026992; DIOX_N.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR InterPro; IPR027443; IPNS-like_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR Pfam; PF14226; DIOX_N; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..360
FT /note="Alpha-ketoglutarate dependent kainoid synthase"
FT /id="PRO_0000454272"
FT DOMAIN 200..310
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 225
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 227
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 286
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 301
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ SEQUENCE 360 AA; 41163 MW; BD06A2E1FAAD0F22 CRC64;
MTVSKYNGVA STFNGVARRF DFAPLEADKL NWYPRSALPP EIPAIDLNKV NTEEELAQFL
VDIRKSGLFY IVDHGIPEEI SIGCYNAFRE FCNLPEEARE KYNTDESFKS GGYVPFKGTS
IGGGNLFERQ KDFVVKFFWR GPSVVNRSPN DRFAEFHDEH HRKTAELAEK IITTILKALK
TRFPEFHPDE LKDNINVRNM FFSNRIYPEA PPDDGEKADY RLVPHRDLSF ITLANQVPAN
NGFKGLFILT GDGEKIPVPP IRNSYLVFIG QGLSYLTNKY LPAALHGVDF PDNTNFEGSE
RASLISFYEP NDYMMPSKNI NPLPEEIFEK SCTFYDDVGV GRAGTTYNYV RYKFHEGYYL
