HCS_KITSK
ID HCS_KITSK Reviewed; 338 AA.
AC E4MYY0;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=(2Z,6E)-hedycaryol synthase {ECO:0000303|PubMed:24399794};
DE Short=HcS {ECO:0000303|PubMed:24399794};
DE EC=4.2.3.187 {ECO:0000269|PubMed:24399794};
GN OrderedLocusNames=KSE_00200t {ECO:0000312|EMBL:BAJ25873.1},
GN KSE_76540t {ECO:0000312|EMBL:BAJ33405.1};
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 X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF ASP-82; PHE-149; MET-181; TRP-309; HIS-310; ARG-315 AND
RP TYR-316, DOMAIN, AND SUBUNIT.
RC STRAIN=ATCC 33774 / DSM 43861 / JCM 3304 / KCC A-0304 / NBRC 14216 /
RC KM-6054;
RX PubMed=24399794; DOI=10.1002/cbic.201300708;
RA Baer P., Rabe P., Citron C.A., de Oliveira Mann C.C., Kaufmann N.,
RA Groll M., Dickschat J.S.;
RT "Hedycaryol synthase in complex with nerolidol reveals terpene cyclase
RT mechanism.";
RL ChemBioChem 15:213-216(2014).
CC -!- FUNCTION: Catalyzes the conversion of (2E,6E)-farnesyl diphosphate
CC (FPP) into (2Z,6E)-hedycaryol via a 1,11-cyclization.
CC {ECO:0000269|PubMed:24399794}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + H2O = (2Z,6E)-hedycaryol +
CC diphosphate; Xref=Rhea:RHEA:54060, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:138044, ChEBI:CHEBI:175763;
CC EC=4.2.3.187; Evidence={ECO:0000269|PubMed:24399794};
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 -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24399794}.
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:24399794}.
CC -!- MISCELLANEOUS: The 1,11-cyclization requires isomerization of (2E,6E)-
CC farnesyl diphosphate (FPP) to nerolidyl diphosphate (NPP), the
CC abstraction of the pyrophosphate from intermediate NPP leading to a
CC (Z,E)-hedycaryl cation and finally an nucleophilic attack of a water
CC molecule. {ECO:0000269|PubMed:24399794}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; AP010968; BAJ25873.1; -; Genomic_DNA.
DR EMBL; AP010968; BAJ33405.1; -; Genomic_DNA.
DR RefSeq; WP_014133196.1; NC_016109.1.
DR PDB; 4MC0; X-ray; 2.70 A; A/B=1-338.
DR PDB; 4MC3; X-ray; 1.50 A; A=1-338.
DR PDB; 4MC8; X-ray; 1.90 A; A=1-338.
DR PDBsum; 4MC0; -.
DR PDBsum; 4MC3; -.
DR PDBsum; 4MC8; -.
DR AlphaFoldDB; E4MYY0; -.
DR SMR; E4MYY0; -.
DR STRING; 452652.KSE_00200t; -.
DR EnsemblBacteria; BAJ25873; BAJ25873; KSE_00200t.
DR EnsemblBacteria; BAJ33405; BAJ33405; KSE_76540t.
DR KEGG; ksk:KSE_00200t; -.
DR KEGG; ksk:KSE_76540t; -.
DR PATRIC; fig|452652.3.peg.18; -.
DR eggNOG; ENOG5033VJC; Bacteria.
DR HOGENOM; CLU_042538_4_0_11; -.
DR OMA; CNDICSF; -.
DR OrthoDB; 1869158at2; -.
DR BRENDA; 4.2.3.187; 13720.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000007076; Chromosome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0010333; F:terpene synthase activity; IDA:UniProtKB.
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 3D-structure; Lyase; Magnesium; Metal-binding; Reference proteome.
FT CHAIN 1..338
FT /note="(2Z,6E)-hedycaryol synthase"
FT /id="PRO_0000444712"
FT MOTIF 82..87
FT /note="DDXXXE motif"
FT /evidence="ECO:0000305|PubMed:24399794"
FT MOTIF 221..229
FT /note="NXXXSXXXE motif"
FT /evidence="ECO:0000305|PubMed:24399794"
FT BINDING 82
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 87
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 87
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 175
FT /ligand="substrate"
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 BINDING 228
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 229
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT SITE 149
FT /note="Important for the cation stabilization at C-11"
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 55
FT /note="S->W: Loss of synthase activity."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 82
FT /note="D->N: Loss of synthase activity at pH 7.0. Strongly
FT reduced synthase activity at pH 8.5."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 149
FT /note="F->L: Loss of synthase activity at pH 7.0. Strongly
FT reduced synthase activity at pH 8.5."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 149
FT /note="F->W: No effect on synthase activity at pH 7 and
FT 8.5."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 181
FT /note="M->H: Loss of synthase activity at pH 7.0. Strongly
FT reduced synthase activity at pH 8.5."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 181
FT /note="M->K: Loss of synthase activity."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 309
FT /note="W->F,L,Y: No effect on synthase activity at pH 7 and
FT 8.5."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 310
FT /note="H->S: Loss of synthase activity."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 315
FT /note="R->K: No effect on synthase activity at pH 7 and
FT 8.5."
FT /evidence="ECO:0000269|PubMed:24399794"
FT MUTAGEN 316
FT /note="Y->F: No effect on synthase activity at pH 7 and
FT 8.5."
FT /evidence="ECO:0000269|PubMed:24399794"
FT HELIX 21..35
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 52..59
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 65..84
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 95..107
FT /evidence="ECO:0007829|PDB:4MC3"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 118..131
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 136..160
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 168..178
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 181..188
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:4MC3"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 204..225
FT /evidence="ECO:0007829|PDB:4MC3"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:4MC8"
FT HELIX 238..246
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 250..282
FT /evidence="ECO:0007829|PDB:4MC3"
FT HELIX 286..309
FT /evidence="ECO:0007829|PDB:4MC3"
SQ SEQUENCE 338 AA; 37591 MW; F671104E7633328C CRC64;
MAEFEIPDFY VPFPLECNPH LEEASRAMWE WIDANGLAPT ERARDRMRRT GADLSGAYVW
PRADLDTLTI GLKWIALTFR IDDQIDEDDT AERLPARMTA IDELRGTLHG LPVSGRSPTA
RALGALWQET ALGRPATWCD AFIGHFEAFL QTYTTEAGLN AHGAGLRLDD YLDRRMYSVG
MPWLWDLDEL RLPIFLPGSV RTCGPMNKLR RAGALHIALV NDVFSVERET LVGYQHNAVT
IIREAQGCSL QEAVDQVAVL VEAQLHTVLQ ARQELLEELD RQALPSRARE AAVDYAANVA
ANLSGQLVWH SSVERYAVDD LQSAADPRAT PTTSSLGI
