TMUUS_STRCL
ID TMUUS_STRCL Reviewed; 418 AA.
AC B5GW45;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=(+)-T-muurolol synthase ((2E,6E)-farnesyl diphosphate cyclizing) {ECO:0000303|PubMed:21276937};
DE EC=4.2.3.98 {ECO:0000269|PubMed:21276937};
DE AltName: Full=Terpene cyclase {ECO:0000303|PubMed:21276937};
DE AltName: Full=Type I terpene synthase {ECO:0000303|PubMed:21276937};
GN ORFNames=SCLAV_p0068, SSCG_03688;
OS Streptomyces clavuligerus.
OG Plasmid pSCL4.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1901;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27064 / DSM 738 / JCM 4710 / NBRC 13307 / NCIMB 12785 / NRRL
RC 3585 / VKM Ac-602; PLASMID=pSCL4;
RX PubMed=20624727; DOI=10.1093/gbe/evq013;
RA Medema M.H., Trefzer A., Kovalchuk A., van den Berg M., Mueller U.,
RA Heijne W., Wu L., Alam M.T., Ronning C.M., Nierman W.C., Bovenberg R.A.L.,
RA Breitling R., Takano E.;
RT "The sequence of a 1.8-mb bacterial linear plasmid reveals a rich
RT evolutionary reservoir of secondary metabolic pathways.";
RL Genome Biol. Evol. 2:212-224(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27064 / DSM 738 / JCM 4710 / NBRC 13307 / NCIMB 12785 / NRRL
RC 3585 / VKM Ac-602;
RA Fischbach M., Ward D., Young S., Jaffe D., Gnerre S., Berlin A., Heiman D.,
RA Hepburn T., Sykes S., Alvarado L., Kodira C.D., Straight P., Clardy J.,
RA Hung D., Kolter R., Mekalanos J., Walker S., Walsh C.T., Lander E.,
RA Galagan J., Nusbaum C., Birren B.;
RT "Annotation of Streptomyces clavuligerus ATCC 27064.";
RL Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND REACTION
RP MECHANISM.
RC STRAIN=ATCC 27064 / DSM 738 / JCM 4710 / NBRC 13307 / NCIMB 12785 / NRRL
RC 3585 / VKM Ac-602;
RX PubMed=21276937; DOI=10.1016/j.chembiol.2010.11.008;
RA Hu Y., Chou W.K., Hopson R., Cane D.E.;
RT "Genome mining in Streptomyces clavuligerus: expression and biochemical
RT characterization of two new cryptic sesquiterpene synthases.";
RL Chem. Biol. 18:32-37(2011).
CC -!- FUNCTION: Catalyzes the conversion of (2E,6E)-farnesyl diphosphate
CC (FPP) into (+)-T-muurolol via a 1,10-cyclization, which requires
CC isomerization of FPP to nerolidyl diphosphate (NPP) and then
CC abstraction of the pyrophosphate from intermediate NPP leading to a
CC (E,Z)-germacradienyl (helminthogermacradienyl) cation.
CC {ECO:0000269|PubMed:21276937}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + H2O = (+)-T-muurolol +
CC diphosphate; Xref=Rhea:RHEA:32011, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:63704, ChEBI:CHEBI:175763;
CC EC=4.2.3.98; Evidence={ECO:0000269|PubMed:21276937};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.7 uM for (2E,6E)-farnesyl diphosphate
CC {ECO:0000269|PubMed:21276937};
CC Note=kcat is 0.00163 sec(-1). {ECO:0000269|PubMed:21276937};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000250|UniProtKB:A7NH01}.
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:0000250|UniProtKB:A7NH01}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; CM000914; EFG03561.2; -; Genomic_DNA.
DR EMBL; DS570654; EDY50541.1; -; Genomic_DNA.
DR RefSeq; WP_003956090.1; NZ_CP027859.1.
DR AlphaFoldDB; B5GW45; -.
DR SMR; B5GW45; -.
DR STRING; 443255.SCLAV_p0068; -.
DR EnsemblBacteria; EDY50541; EDY50541; SSCG_03688.
DR KEGG; ag:EFG03561; -.
DR eggNOG; COG3170; Bacteria.
DR OMA; AMETWVI; -.
DR OrthoDB; 1869158at2; -.
DR BRENDA; 4.2.3.98; 5988.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000002357; Plasmid pSCL4.
DR Proteomes; UP000006569; Unassembled WGS sequence.
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; Plasmid; Reference proteome.
FT CHAIN 1..418
FT /note="(+)-T-muurolol synthase ((2E,6E)-farnesyl
FT diphosphate cyclizing)"
FT /id="PRO_0000418478"
FT REGION 354..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 83..88
FT /note="DDXXXD motif"
FT /evidence="ECO:0000250|UniProtKB:A7NH01"
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 88
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 88
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 179
FT /ligand="substrate"
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 229
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 233
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT BINDING 312..313
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT SITE 80
FT /note="Plays a critical role in the stabilization of
FT intermediate cation"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT SITE 84
FT /note="Plays a critical role for substrate recognition"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT SITE 159
FT /note="Plays a critical role for substrate recognition"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
FT SITE 183
FT /note="Plays a critical role for abstraction of the
FT pyrophosphate group"
FT /evidence="ECO:0000250|UniProtKB:B5HDJ6"
SQ SEQUENCE 418 AA; 46002 MW; C0F63991CF0F4C1E CRC64;
MSLNHSDLMF YCPVDDLPHP AASGVNDRTL DWASGQGIPT ADRDAGRLRA MAPGLLAARI
APDARGPVLD AFADHHTWLF AFDDEYCDRA DGSGITEWAS FLARLHRVVE TGESALLPGN
PYGLALRDIA CRLSTYTTPA QLAEWLEALR SYFAALVWER SRRRDDDRLQ SLDDYLLLRL
RNGAMHTSIT LLDTVNGYVL PRELRETPGV RALVEMTALL VSVDNDILSH HKESTSGTRE
ANLLDVLGRT GHTTPGEAVA QAVALRNEIM RQFVRVAERV RTPAAVPELY RFTTGLARWI
RANLDFSLTT TRYTGPVTER AALSPHEVPP LSGQGPAPAR SDVIGWWWRI PEPLPEPGSD
GADTPVRKRR AGDRPPTAGR GGAPHHQRTG PPPPVLPGGI TASRSSGLQQ STWRREHR
