OLIAC_CANSA
ID OLIAC_CANSA Reviewed; 101 AA.
AC I6WU39;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=Olivetolic acid cyclase {ECO:0000303|PubMed:22802619};
DE EC=4.4.1.26 {ECO:0000269|PubMed:22802619, ECO:0000269|PubMed:26783002};
GN Name=OAC {ECO:0000303|PubMed:22802619};
OS Cannabis sativa (Hemp) (Marijuana).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; fabids; Rosales; Cannabaceae; Cannabis.
OX NCBI_TaxID=3483;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, 3D-STRUCTURE MODELING, SUBUNIT, AND
RP MUTAGENESIS OF LYS-4; HIS-5; LYS-12; LYS-38; ASP-45; HIS-57; HIS-75; HIS-78
RP AND ASP-96.
RC STRAIN=cv. Finola;
RX PubMed=22802619; DOI=10.1073/pnas.1200330109;
RA Gagne S.J., Stout J.M., Liu E., Boubakir Z., Clark S.M., Page J.E.;
RT "Identification of olivetolic acid cyclase from Cannabis sativa reveals a
RT unique catalytic route to plant polyketides.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12811-12816(2012).
RN [2]
RP REVIEW.
RX PubMed=17712812; DOI=10.1002/cbdv.200790145;
RA Taura F., Sirikantaramas S., Shoyama Y., Shoyama Y., Morimoto S.;
RT "Phytocannabinoids in Cannabis sativa: recent studies on biosynthetic
RT enzymes.";
RL Chem. Biodivers. 4:1649-1663(2007).
RN [3]
RP PATHWAY, AND REVIEW.
RX PubMed=30468448; DOI=10.1039/c8np00077h;
RA Liu Y., Jing S.-X., Luo S.-H., Li S.-H.;
RT "Non-volatile natural products in plant glandular trichomes: chemistry,
RT biological activities and biosynthesis.";
RL Nat. Prod. Rep. 36:626-665(2019).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.32 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-5; ILE-7; PHE-24;
RP TYR-27; VAL-59; TYR-72; HIS-75 AND HIS-78.
RX PubMed=26783002; DOI=10.1111/febs.13654;
RA Yang X., Matsui T., Kodama T., Mori T., Zhou X., Taura F., Noguchi H.,
RA Abe I., Morita H.;
RT "Structural basis for olivetolic acid formation by a polyketide cyclase
RT from Cannabis sativa.";
RL FEBS J. 283:1088-1106(2016).
CC -!- FUNCTION: Involved in the biosynthesis of cannabinoids-related
CC terpenophenolic natural products, which have pharmacological activity
CC (PubMed:22802619). Polyketide cyclase which functions in concert with
CC OLS/TKS to form olivetolic acid (PubMed:22802619, PubMed:26783002). Has
CC no intrinsic polyketide synthase activity and requires the presence of
CC OLS to produce olivetolic acid (PubMed:22802619).
CC {ECO:0000269|PubMed:22802619, ECO:0000269|PubMed:26783002}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,5,7-trioxododecanoyl-CoA = CoA + H(+) + olivetolate;
CC Xref=Rhea:RHEA:34123, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:66950, ChEBI:CHEBI:66957; EC=4.4.1.26;
CC Evidence={ECO:0000269|PubMed:22802619, ECO:0000269|PubMed:26783002};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34124;
CC Evidence={ECO:0000269|PubMed:22802619, ECO:0000269|PubMed:26783002};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000303|PubMed:30468448}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22802619}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22802619}.
CC -!- TISSUE SPECIFICITY: Expressed in glandular trichomes and at lower
CC levels in female flowers. {ECO:0000269|PubMed:22802619}.
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DR EMBL; JN679224; AFN42527.1; -; mRNA.
DR PDB; 5B08; X-ray; 1.32 A; A/B=1-101.
DR PDB; 5B09; X-ray; 1.70 A; A=1-101.
DR PDB; 5B0A; X-ray; 2.10 A; A/B=1-101.
DR PDB; 5B0B; X-ray; 2.19 A; A/B/C/D=1-101.
DR PDB; 5B0C; X-ray; 1.60 A; A/B=1-101.
DR PDB; 5B0D; X-ray; 1.80 A; A/B=1-101.
DR PDB; 5B0E; X-ray; 1.60 A; A/B=1-101.
DR PDB; 5B0F; X-ray; 1.60 A; A/B=1-101.
DR PDB; 5B0G; X-ray; 1.40 A; A=1-101.
DR PDB; 7W6D; X-ray; 1.54 A; A/B=1-101.
DR PDB; 7W6E; X-ray; 1.38 A; A/B=1-101.
DR PDB; 7W6F; X-ray; 1.58 A; A/B=1-101.
DR PDBsum; 5B08; -.
DR PDBsum; 5B09; -.
DR PDBsum; 5B0A; -.
DR PDBsum; 5B0B; -.
DR PDBsum; 5B0C; -.
DR PDBsum; 5B0D; -.
DR PDBsum; 5B0E; -.
DR PDBsum; 5B0F; -.
DR PDBsum; 5B0G; -.
DR PDBsum; 7W6D; -.
DR PDBsum; 7W6E; -.
DR PDBsum; 7W6F; -.
DR AlphaFoldDB; I6WU39; -.
DR SMR; I6WU39; -.
DR EnsemblPlants; novel_model_6007_5bd9a17a; cds.novel_model_6007_5bd9a17a; novel_gene_3079_5bd9a17a.
DR EnsemblPlants; novel_model_6008_5bd9a17a.2.5bd9b13b; cds.novel_model_6008_5bd9a17a.2.5bd9b13b; novel_gene_3079_5bd9a17a.
DR EnsemblPlants; novel_model_6009_5bd9a17a.1.5bd9b13b; cds.novel_model_6009_5bd9a17a.1.5bd9b13b; novel_gene_3079_5bd9a17a.
DR Gramene; novel_model_6007_5bd9a17a; cds.novel_model_6007_5bd9a17a; novel_gene_3079_5bd9a17a.
DR Gramene; novel_model_6008_5bd9a17a.2.5bd9b13b; cds.novel_model_6008_5bd9a17a.2.5bd9b13b; novel_gene_3079_5bd9a17a.
DR Gramene; novel_model_6009_5bd9a17a.1.5bd9b13b; cds.novel_model_6009_5bd9a17a.1.5bd9b13b; novel_gene_3079_5bd9a17a.
DR KEGG; ag:AFN42527; -.
DR BioCyc; MetaCyc:MON-17640; -.
DR BRENDA; 4.4.1.26; 1159.
DR UniPathway; UPA00213; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0009975; F:cyclase activity; IDA:UniProtKB.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1901696; P:cannabinoid biosynthetic process; IDA:UniProtKB.
DR GO; GO:1901697; P:olivetolic acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR013097; Dabb.
DR InterPro; IPR011008; Dimeric_a/b-barrel.
DR InterPro; IPR044662; HS1/DABB1-like.
DR PANTHER; PTHR33178; PTHR33178; 1.
DR Pfam; PF07876; Dabb; 1.
DR SMART; SM00886; Dabb; 1.
DR SUPFAM; SSF54909; SSF54909; 1.
DR PROSITE; PS51502; S_R_A_B_BARREL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Lyase; Magnesium; Metal-binding.
FT CHAIN 1..101
FT /note="Olivetolic acid cyclase"
FT /id="PRO_0000421155"
FT DOMAIN 3..97
FT /note="Stress-response A/B barrel"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00835"
FT ACT_SITE 72
FT /note="Acid/base catalyst"
FT /evidence="ECO:0000269|PubMed:26783002"
FT ACT_SITE 75
FT /note="Acid/base catalyst"
FT /evidence="ECO:0000269|PubMed:26783002"
FT BINDING 5
FT /ligand="3,5,7-trioxododecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:66957"
FT /evidence="ECO:0000269|PubMed:26783002,
FT ECO:0007744|PDB:5B09"
FT BINDING 31
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 37
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="3,5,7-trioxododecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:66957"
FT /evidence="ECO:0000269|PubMed:26783002,
FT ECO:0007744|PDB:5B09"
FT MUTAGEN 4
FT /note="K->A: No effect."
FT /evidence="ECO:0000269|PubMed:22802619"
FT MUTAGEN 5
FT /note="H->A: Total loss of activity."
FT /evidence="ECO:0000269|PubMed:22802619,
FT ECO:0000269|PubMed:26783002"
FT MUTAGEN 5
FT /note="H->L,Q,S: Reduced activity."
FT /evidence="ECO:0000269|PubMed:26783002"
FT MUTAGEN 7
FT /note="I->L,F: Slightly reduced activity."
FT /evidence="ECO:0000269|PubMed:26783002"
FT MUTAGEN 12
FT /note="K->A: No effect."
FT /evidence="ECO:0000269|PubMed:22802619"
FT MUTAGEN 24
FT /note="F->L: Reduced activity."
FT /evidence="ECO:0000269|PubMed:26783002"
FT MUTAGEN 27
FT /note="Y->F: Increased activity."
FT /evidence="ECO:0000269|PubMed:26783002"
FT MUTAGEN 27
FT /note="Y->L,M,W: Reduced activity."
FT /evidence="ECO:0000269|PubMed:26783002"
FT MUTAGEN 38
FT /note="K->A: No effect."
FT /evidence="ECO:0000269|PubMed:22802619"
FT MUTAGEN 45
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:22802619"
FT MUTAGEN 57
FT /note="H->A: Total loss of activity."
FT /evidence="ECO:0000269|PubMed:22802619"
FT MUTAGEN 59
FT /note="V->M: Slightly reduced activity."
FT /evidence="ECO:0000269|PubMed:26783002"
FT MUTAGEN 72
FT /note="Y->F: Total loss of activity."
FT /evidence="ECO:0000269|PubMed:26783002"
FT MUTAGEN 75
FT /note="H->A: 99% loss of activity."
FT /evidence="ECO:0000269|PubMed:22802619,
FT ECO:0000269|PubMed:26783002"
FT MUTAGEN 78
FT /note="H->A,N,Q,S: Total loss of activity."
FT /evidence="ECO:0000269|PubMed:22802619,
FT ECO:0000269|PubMed:26783002"
FT MUTAGEN 96
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:22802619"
FT STRAND 3..11
FT /evidence="ECO:0007829|PDB:5B08"
FT HELIX 17..29
FT /evidence="ECO:0007829|PDB:5B08"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:5B08"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:5B08"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:5B08"
FT STRAND 57..65
FT /evidence="ECO:0007829|PDB:5B08"
FT HELIX 66..73
FT /evidence="ECO:0007829|PDB:5B08"
FT HELIX 76..85
FT /evidence="ECO:0007829|PDB:5B08"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:5B08"
FT STRAND 89..97
FT /evidence="ECO:0007829|PDB:5B08"
SQ SEQUENCE 101 AA; 12002 MW; 9AB0CCAFDA217482 CRC64;
MAVKHLIVLK FKDEITEAQK EEFFKTYVNL VNIIPAMKDV YWGKDVTQKN KEEGYTHIVE
VTFESVETIQ DYIIHPAHVG FGDVYRSFWE KLLIFDYTPR K
