CEABS_KITSK
ID CEABS_KITSK Reviewed; 320 AA.
AC E4N7E5;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 1.
DT 03-AUG-2022, entry version 52.
DE RecName: Full=(+)-corvol ether B synthase/(+)-corvol ether A synthase ((2E,6E)-farnesyl diphosphate cyclizing) {ECO:0000303|PubMed:25809275};
DE EC=4.2.3.163 {ECO:0000269|PubMed:25809275, ECO:0000269|PubMed:27666571};
DE EC=4.2.3.171 {ECO:0000269|PubMed:25809275, ECO:0000269|PubMed:27666571};
DE AltName: Full=Terpene synthase {ECO:0000303|PubMed:25809275};
DE AltName: Full=Type I terpene cyclase {ECO:0000303|PubMed:25809275};
GN OrderedLocusNames=KSE_12950 {ECO:0000312|EMBL:BAJ27126.1};
OS Kitasatospora setae (strain ATCC 33774 / DSM 43861 / JCM 3304 / KCC A-0304
OS / NBRC 14216 / KM-6054) (Streptomyces setae).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Kitasatospora.
OX NCBI_TaxID=452652;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 33774 / DSM 43861 / JCM 3304 / KCC A-0304 / NBRC 14216 /
RC KM-6054 {ECO:0000312|Proteomes:UP000007076};
RX PubMed=21059706; DOI=10.1093/dnares/dsq026;
RA Ichikawa N., Oguchi A., Ikeda H., Ishikawa J., Kitani S., Watanabe Y.,
RA Nakamura S., Katano Y., Kishi E., Sasagawa M., Ankai A., Fukui S.,
RA Hashimoto Y., Kamata S., Otoguro M., Tanikawa S., Nihira T., Horinouchi S.,
RA Ohnishi Y., Hayakawa M., Kuzuyama T., Arisawa A., Nomoto F., Miura H.,
RA Takahashi Y., Fujita N.;
RT "Genome sequence of Kitasatospora setae NBRC 14216T: an evolutionary
RT snapshot of the family Streptomycetaceae.";
RL DNA Res. 17:393-406(2010).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND REACTION
RP MECHANISM.
RC STRAIN=ATCC 33774 / DSM 43861 / JCM 3304 / KCC A-0304 / NBRC 14216 /
RC KM-6054;
RX PubMed=25809275; DOI=10.1002/anie.201501119;
RA Rabe P., Pahirulzaman K.A., Dickschat J.S.;
RT "Structures and biosynthesis of corvol ethers--sesquiterpenes from the
RT actinomycete Kitasatospora setae.";
RL Angew. Chem. Int. Ed. 54:6041-6045(2015).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND REACTION MECHANISM.
RC STRAIN=ATCC 33774 / DSM 43861 / JCM 3304 / KCC A-0304 / NBRC 14216 /
RC KM-6054;
RX PubMed=27666571; DOI=10.1002/anie.201608042;
RA Rinkel J., Rabe P., Garbeva P., Dickschat J.S.;
RT "Lessons from 1,3-hydride shifts in sesquiterpene cyclizations.";
RL Angew. Chem. Int. Ed. 55:13593-13596(2016).
CC -!- FUNCTION: Catalyzes the conversion of (2E,6E)-farnesyl diphosphate
CC (FPP) into (+)-corvol ether A and (+)-corvol ether B via a 1,10-
CC cyclization, which requires isomerization of FPP to nerolidyl
CC diphosphate (NPP) and then abstraction of the pyrophosphate from
CC intermediate NPP leading to a (E,Z)-germacradienyl
CC (helminthogermacradienyl) cation (PubMed:25809275, PubMed:27666571).
CC The preferred substrate is (2E,6E)-farnesyl diphosphate (FPP), however
CC geranyl diphosphate (GPP) is also able to produce small amounts of
CC several acyclic and cyclic monoterpenes, with linalool as the main
CC product (PubMed:25809275). {ECO:0000269|PubMed:25809275,
CC ECO:0000269|PubMed:27666571}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + H2O = (+)-corvol ether B +
CC diphosphate; Xref=Rhea:RHEA:53644, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:137536, ChEBI:CHEBI:175763;
CC EC=4.2.3.163; Evidence={ECO:0000269|PubMed:25809275,
CC ECO:0000269|PubMed:27666571};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + H2O = (+)-corvol ether A +
CC diphosphate; Xref=Rhea:RHEA:53648, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:137535, ChEBI:CHEBI:175763;
CC EC=4.2.3.171; Evidence={ECO:0000269|PubMed:25809275,
CC ECO:0000269|PubMed:27666571};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:B5HDJ6};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:B5HDJ6};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305}.
CC -!- DOMAIN: The Asp-Asp-Xaa-Xaa-Xaa-Asp (DDXXXD) motif is important for the
CC catalytic activity, presumably through binding to Mg(2+).
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; AP010968; BAJ27126.1; -; Genomic_DNA.
DR RefSeq; WP_014134444.1; NC_016109.1.
DR AlphaFoldDB; E4N7E5; -.
DR SMR; E4N7E5; -.
DR STRING; 452652.KSE_12950; -.
DR EnsemblBacteria; BAJ27126; BAJ27126; KSE_12950.
DR KEGG; ksk:KSE_12950; -.
DR PATRIC; fig|452652.3.peg.1291; -.
DR eggNOG; ENOG502Z881; Bacteria.
DR HOGENOM; CLU_042538_2_1_11; -.
DR OMA; DLIEYAM; -.
DR OrthoDB; 1869158at2; -.
DR BRENDA; 4.2.3.163; 13720.
DR BRENDA; 4.2.3.171; 13720.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000007076; Chromosome.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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; Reference proteome.
FT CHAIN 1..320
FT /note="(+)-corvol ether B synthase/(+)-corvol ether A
FT synthase ((2E,6E)-farnesyl diphosphate cyclizing)"
FT /id="PRO_0000443247"
FT MOTIF 78..83
FT /note="DDXXXD motif"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 78
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 83
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 83
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 217
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 221
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 225
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT SITE 75
FT /note="Plays a critical role in the stabilization of
FT intermediate cation"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT SITE 79
FT /note="Plays a critical role for substrate recognition"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
SQ SEQUENCE 320 AA; 36227 MW; 6E4B62E2943A507D CRC64;
MIPRFDFPWP SACHPHARQA EQGALAFAER HGLVPTAAYR SRLERTRYGW LAARCYPDAD
DVLLQLCADY FIWFFIVDDL FVDRVDTLSE RTIPNLTAMI DVLDHHRPGA EPVFGEHAWL
DVCTRLRAYL SDEHFQRFAH GMRMWAATAG LQIANHLGAD TVDVAPYETI RRHTSGTNPC
LALADAAKHG PVTPAEYHSP PVQRLVLHAN NVVCWSNDVQ SLKMELNQPG QYWNMAAIYA
HRGLSLQQAV DLVALRVRGE IASFQSLALT LEPHASRPLR GFVDGLRHWM RGYQDWVEND
TLRYADAFIA EDADDTAVRT
