CLDD_STRCP
ID CLDD_STRCP Reviewed; 329 AA.
AC A0A0H5BN57;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2015, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=(12E)-labda-8(17),12,14-triene synthase {ECO:0000303|PubMed:26814669};
DE EC=4.2.3.193 {ECO:0000269|PubMed:26814669};
DE AltName: Full=Type-A diterpene synthase {ECO:0000303|PubMed:26814669};
GN Name=cldD {ECO:0000303|PubMed:26814669};
OS Streptomyces cyslabdanicus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1470456;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DOMAIN.
RC STRAIN=DSM 42135 / NBRC 110081 / K04-0144;
RX PubMed=26507838; DOI=10.1007/s10295-015-1694-6;
RA Ikeda H., Shin-ya K., Nagamitsu T., Tomoda H.;
RT "Biosynthesis of mercapturic acid derivative of the labdane-type diterpene,
RT cyslabdan that potentiates imipenem activity against methicillin-resistant
RT Staphylococcus aureus: cyslabdan is generated by mycothiol-mediated
RT xenobiotic detoxification.";
RL J. Ind. Microbiol. Biotechnol. 43:325-342(2016).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND DOMAIN.
RC STRAIN=DSM 42135 / NBRC 110081 / K04-0144;
RX PubMed=26814669; DOI=10.1038/ja.2015.147;
RA Yamada Y., Komatsu M., Ikeda H.;
RT "Chemical diversity of labdane-type bicyclic diterpene biosynthesis in
RT Actinomycetales microorganisms.";
RL J. Antibiot. 69:515-523(2016).
CC -!- FUNCTION: Involved in the biosynthesis of the mercapturic acid
CC derivative diterpene cyslabdan A, a potentiator of the beta-lactam
CC antibiotic imipenem (PubMed:26507838). Catalyzes the conversion of (+)-
CC copalyl diphosphate to yield labda-8(17),12(E),14-triene (biformene)
CC (PubMed:26507838, PubMed:26814669). {ECO:0000269|PubMed:26507838,
CC ECO:0000269|PubMed:26814669}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-copalyl diphosphate = (12E)-labda-8(17),12,14-triene +
CC diphosphate; Xref=Rhea:RHEA:54640, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58635, ChEBI:CHEBI:138302; EC=4.2.3.193;
CC Evidence={ECO:0000305|PubMed:26814669};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:26814669};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:B5HDJ6};
CC -!- DOMAIN: The Asp-Asp-Xaa-Xaa-Xaa-Glu (DDXXXE) and Asn-Xaa-Xaa-Xaa-Ser-
CC Xaa-Xaa-Xaa-Glu (NSE) motifs are important for the catalytic activity,
CC presumably through binding to Mg(2+). {ECO:0000305|PubMed:26507838,
CC ECO:0000305|PubMed:26814669}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; LC064028; BAR97453.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0H5BN57; -.
DR SMR; A0A0H5BN57; -.
DR KEGG; ag:BAR97453; -.
DR BRENDA; 4.2.3.193; 15347.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR034686; Terpene_cyclase-like_2.
DR SFLD; SFLDG01020; Terpene_Cyclase_Like_2; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Lyase; Magnesium; Metal-binding.
FT CHAIN 1..329
FT /note="(12E)-labda-8(17),12,14-triene synthase"
FT /id="PRO_0000444807"
FT MOTIF 90..95
FT /note="DDXXXE motif"
FT /evidence="ECO:0000305|PubMed:26507838,
FT ECO:0000305|PubMed:26814669"
FT MOTIF 230..238
FT /note="NXXXSXXXE motif"
FT /evidence="ECO:0000305|PubMed:26507838,
FT ECO:0000305|PubMed:26814669"
FT BINDING 90
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 95
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 95
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 184
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 230
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 234
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 237
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 238
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 316..317
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
SQ SEQUENCE 329 AA; 35699 MW; 31E1296F32AE6AF8 CRC64;
MTRTGDAVTI LPQPDFTATF PGPFPTSPHG ERTERQLLGW LEEYPLLPSA RARSVLVNIT
SHGVSRTLPT ADADDLVLFA ELLLWLTAFD DMHGESNAAR DLVALVDRTA ELTLVLAGGS
PPPLTNPFPA ALYDLLARFR ARTGPAAYLR LAASLRDTIM ALVWEAHHVA EPERVALETY
LEMRPHTVFV RTIFAAAEIV LDYELTDAQR ALAPVRHLET AVANLAGWIN DLASYEREAA
RGPAQPLSLP TLLRARHGGS LEEAFARAGG MCENEAAVAR QGITSLAGDP PSALTAHARA
LEDIARSFVW HTSHARYQGP KRGAAPTSR
