KABA_DIGSM
ID KABA_DIGSM Reviewed; 439 AA.
AC A0A4D6IA24;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 5.
DE RecName: Full=Magnesium-dependent glutamate N-prenyltransferase {ECO:0000303|PubMed:30995339};
DE EC=2.5.1.- {ECO:0000269|PubMed:30995339, ECO:0000269|PubMed:32457155};
DE AltName: Full=Kainic acid biosynthesis cluster protein A {ECO:0000303|PubMed:30995339};
DE Short=DsKabA {ECO:0000303|PubMed:30995339};
GN Name=kabA {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, AND
RP PATHWAY.
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).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF MET-114.
RX PubMed=32457155; DOI=10.1073/pnas.2001325117;
RA Chekan J.R., McKinnie S.M.K., Noel J.P., Moore B.S.;
RT "Algal neurotoxin biosynthesis repurposes the terpene cyclase structural
RT fold into an N-prenyltransferase.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:12799-12805(2020).
CC -!- FUNCTION: Magnesium-dependent glutamate N-prenyltransferase: part of
CC the gene 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 L-glutamic acid (L-Glu)
CC to prekainic acid in the presence of dimethylallyl diphosphate (DMAPP)
CC (PubMed:30995339, PubMed:32457155). Can also use geranyl diphosphate
CC (GPP) as substrate, thus leading to the formation of N-geranyl-L-
CC glutamic acid (L-NGG) (PubMed:32457155, PubMed:30995339).
CC {ECO:0000269|PubMed:30995339, ECO:0000269|PubMed:32457155}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + L-glutamate = diphosphate +
CC prekainate; Xref=Rhea:RHEA:67476, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:170011;
CC Evidence={ECO:0000269|PubMed:30995339, ECO:0000269|PubMed:32457155};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67477;
CC Evidence={ECO:0000269|PubMed:30995339, ECO:0000269|PubMed:32457155};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A0A386KZ50};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=89 uM for geranyl diphosphate {ECO:0000269|PubMed:32457155};
CC KM=1.1 uM for dimethylallyl diphosphate
CC {ECO:0000269|PubMed:32457155};
CC Note=kcat is 0.29 min(-1) with geranyl diphosphate as substrate
CC (PubMed:32457155). kcat is 1.3 min(-1) with dimethylallyl diphosphate
CC as substrate (PubMed:32457155). {ECO:0000269|PubMed:32457155};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30995339}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; MK312630; QCC62379.1; -; Genomic_DNA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Magnesium; Metal-binding; Transferase.
FT CHAIN 1..439
FT /note="Magnesium-dependent glutamate N-prenyltransferase"
FT /id="PRO_0000454271"
FT BINDING 322
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A386KZ50"
FT BINDING 326
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A386KZ50"
FT BINDING 330
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A386KZ50"
FT BINDING 330
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A386KZ50"
FT BINDING 337
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A386KZ50"
FT MUTAGEN 114
FT /note="M->T: Increased affinity for geranyl diphosphate
FT (GPP) leading to an enhanced catalytic efficiency with GPP
FT as substrate, but reduced activity with dimethylallyl
FT diphosphate (DMAPP)."
FT /evidence="ECO:0000269|PubMed:32457155"
SQ SEQUENCE 439 AA; 51687 MW; 6EB5B9C60545878E CRC64;
MSITTMKGVT SESPAEALSR FQTTGLTLNN PKDLYWMTEF LKEEFYDKGN YYYPIKTVCD
GELIETELFC PFEPKLSPHY IQLYNSRDER SNLYAVPPKK TDMKKYNRIN CEKMGSLMAP
NSNYDDTEMV SLFYSMMYYL NDQTAHLKLP EEDIQPELVD ELNDHVLQYL SVFLSIFKPR
EPQDLERIWN FLDFYQPYFK KVDGKIILHE KYQGRTPPQI GLIKKITGYV LERFAPKKNI
TQVIYEVIRY IKGIKQEIKI RGDKSFTLSL KEYDEFRDQV TSSPMAHSIT DLTYDDFSYK
AYMNPLFIKL EDLTSEIITY FNDVCTCDRE RLDDDPFNSV FILRDLHSLN YVKSCDLVVK
HAHDKLSKFL EIKQTLLKES TNENEKKAIA QMIKTREDSL IGYTIHEICC VTNGYARDHK
PLMKDYLEKN IFKKLKATN
