ARIS_ASPTE
ID ARIS_ASPTE Reviewed; 320 AA.
AC Q9UR08;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Aristolochene synthase;
DE Short=AS;
DE EC=4.2.3.9;
DE AltName: Full=Sesquiterpene cyclase;
GN Name=Ari1;
OS Aspergillus terreus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=33178;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 35-48;
RP 183-195 AND 215-226, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=ATCC 20516 / NRRL 11156;
RX PubMed=10775423; DOI=10.1006/abbi.2000.1734;
RA Cane D.E., Kang I.;
RT "Aristolochene synthase: purification, molecular cloning, high-level
RT expression in Escherichia coli, and characterization of the Aspergillus
RT terreus cyclase.";
RL Arch. Biochem. Biophys. 376:354-364(2000).
RN [2]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF GLU-227.
RX PubMed=15186158; DOI=10.1021/ja0499593;
RA Felicetti B., Cane D.E.;
RT "Aristolochene synthase: mechanistic analysis of active site residues by
RT site-directed mutagenesis.";
RL J. Am. Chem. Soc. 126:7212-7221(2004).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH MAGNESIUM, AND
RP SUBUNIT.
RX PubMed=17261032; DOI=10.1021/bi0622524;
RA Shishova E.Y., Di Costanzo L., Cane D.E., Christianson D.W.;
RT "X-ray crystal structure of aristolochene synthase from Aspergillus terreus
RT and evolution of templates for the cyclization of farnesyl diphosphate.";
RL Biochemistry 46:1941-1951(2007).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) IN COMPLEX WITH SUBSTRATE; SUBSTRATE
RP ANALOGS AND MAGNESIUM.
RX PubMed=18385128; DOI=10.1074/jbc.m800659200;
RA Shishova E.Y., Yu F., Miller D.J., Faraldos J.A., Zhao Y., Coates R.M.,
RA Allemann R.K., Cane D.E., Christianson D.W.;
RT "X-ray crystallographic studies of substrate binding to aristolochene
RT synthase suggest a metal ion binding sequence for catalysis.";
RL J. Biol. Chem. 283:15431-15439(2008).
CC -!- FUNCTION: Catalyzes the cyclization of trans,trans-farnesyl diphosphate
CC (FPP) to the bicyclic sesquiterpene aristolochene. Produces germacrene
CC A as an enzyme-bound intermediate that is not released by the enzyme,
CC but is further cyclized to produce aristolochene. Aristolochene is the
CC likely parent compound for a number of sesquiterpenoid toxins produced
CC by filamentous fungi. {ECO:0000269|PubMed:10775423,
CC ECO:0000269|PubMed:15186158}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate = (+)-aristolochene +
CC diphosphate; Xref=Rhea:RHEA:19825, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:43445, ChEBI:CHEBI:175763; EC=4.2.3.9;
CC Evidence={ECO:0000269|PubMed:10775423};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:18385128};
CC Note=Binds 3 Mg(2+) ions per monomer. {ECO:0000269|PubMed:18385128};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13.5 nM for (2E,6E)-farnesyl diphosphate
CC {ECO:0000269|PubMed:10775423, ECO:0000269|PubMed:15186158};
CC Vmax=23.6 nmol/min/mg enzyme {ECO:0000269|PubMed:10775423,
CC ECO:0000269|PubMed:15186158};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:10775423,
CC ECO:0000269|PubMed:15186158};
CC -!- PATHWAY: Sesquiterpene biosynthesis; aristolochene biosynthesis;
CC aristolochene from farnesyl diphosphate: step 1/1.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17261032,
CC ECO:0000269|PubMed:18385128}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; AF198359; AAF13263.1; -; mRNA.
DR EMBL; AF198360; AAF13264.1; -; Genomic_DNA.
DR PDB; 2E4O; X-ray; 2.20 A; A/B/C/D=1-320.
DR PDB; 2OA6; X-ray; 2.15 A; A/B/C/D=1-320.
DR PDB; 3BNX; X-ray; 2.10 A; A/B/C/D=1-320.
DR PDB; 3BNY; X-ray; 1.89 A; A/B/C/D=1-320.
DR PDB; 3CKE; X-ray; 2.40 A; A/B/C/D=1-320.
DR PDB; 4KUX; X-ray; 1.90 A; A/B/C/D=14-320.
DR PDB; 4KVD; X-ray; 2.40 A; A/B/C/D=14-320.
DR PDB; 4KVI; X-ray; 2.15 A; A/B/C/D=14-320.
DR PDB; 4KVW; X-ray; 2.10 A; A/B/C/D=14-320.
DR PDB; 4KVY; X-ray; 1.95 A; A/B/C/D=14-320.
DR PDB; 4KWD; X-ray; 1.86 A; A/B/C/D=14-320.
DR PDB; 5IMI; X-ray; 2.46 A; A/B/C/D=14-320.
DR PDB; 5IMN; X-ray; 2.53 A; A/B/C/D=14-320.
DR PDB; 5IMP; X-ray; 2.04 A; A/B/C/D=14-320.
DR PDB; 5IN8; X-ray; 2.35 A; A/B/C/D=14-320.
DR PDB; 5IVG; X-ray; 1.95 A; A/B/C/D=14-320.
DR PDBsum; 2E4O; -.
DR PDBsum; 2OA6; -.
DR PDBsum; 3BNX; -.
DR PDBsum; 3BNY; -.
DR PDBsum; 3CKE; -.
DR PDBsum; 4KUX; -.
DR PDBsum; 4KVD; -.
DR PDBsum; 4KVI; -.
DR PDBsum; 4KVW; -.
DR PDBsum; 4KVY; -.
DR PDBsum; 4KWD; -.
DR PDBsum; 5IMI; -.
DR PDBsum; 5IMN; -.
DR PDBsum; 5IMP; -.
DR PDBsum; 5IN8; -.
DR PDBsum; 5IVG; -.
DR AlphaFoldDB; Q9UR08; -.
DR SMR; Q9UR08; -.
DR BRENDA; 4.2.3.9; 536.
DR SABIO-RK; Q9UR08; -.
DR UniPathway; UPA00177; UER00582.
DR EvolutionaryTrace; Q9UR08; -.
DR GO; GO:0045483; F:aristolochene synthase activity; IEA:UniProtKB-EC.
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 SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Lyase; Magnesium; Metal-binding.
FT CHAIN 1..320
FT /note="Aristolochene synthase"
FT /id="PRO_0000418550"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 90
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17261032,
FT ECO:0000269|PubMed:18385128"
FT BINDING 90
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17261032,
FT ECO:0000269|PubMed:18385128"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18385128"
FT BINDING 219
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:17261032,
FT ECO:0000269|PubMed:18385128"
FT BINDING 223
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:17261032,
FT ECO:0000269|PubMed:18385128"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18385128"
FT BINDING 227
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:17261032,
FT ECO:0000269|PubMed:18385128"
FT BINDING 314..315
FT /ligand="substrate"
FT MUTAGEN 227
FT /note="E->Q: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:15186158"
FT HELIX 29..43
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 49..58
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 60..67
FT /evidence="ECO:0007829|PDB:4KWD"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 76..92
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 98..112
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 123..138
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 140..144
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 160..163
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 168..178
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 181..192
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 198..203
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 205..233
FT /evidence="ECO:0007829|PDB:4KWD"
FT TURN 236..239
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 244..252
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 256..283
FT /evidence="ECO:0007829|PDB:4KWD"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:4KVW"
FT HELIX 289..311
FT /evidence="ECO:0007829|PDB:4KWD"
FT HELIX 313..316
FT /evidence="ECO:0007829|PDB:4KWD"
SQ SEQUENCE 320 AA; 36481 MW; 73190707711ADC2E CRC64;
MKKPNGTNGA SSSLEPPPST FQPLCHPLVE EVSKEVDGYF LQHWNFPNEK ARKKFVAAGF
SRVTCLYFPK ALDDRIHFAC RLLTVLFLID DLLEYMSFEE GSAYNEKLIP ISRGDVLPDR
SIPVEYIIYD LWESMRAHDR EMADEILEPV FLFMRAQTDR TRARPMGLGG YLEYRERDVG
KELLAALMRF SMGLKLSPSE LQRVREIDAN CSKHLSVVND IYSYEKELYT SKTAHSEGGI
LCTSVQILAQ EADVTAEAAK RVLFVMCREW ELRHQLLVAR LSAEGLETPG LAAYVEGLEY
QMSGNELWSQ TTLRYSVVVD
