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Protein

Aristolochene synthase

Gene

ARI1

Organism
Penicillium roqueforti
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene. Produces germacrene A as an enzyme-bound intermediate that is not released by the enzyme, but is further cyclized to produce aristolochene. Aristolochene is the likely parent compound for a number of sesquiterpenoid toxins produced by filamentous fungi.2 Publications

Catalytic activityi

(2E,6E)-farnesyl diphosphate = aristolochene + diphosphate.1 Publication

Cofactori

Mg2+By similarityNote: Binds 3 Mg2+ ions per subunit.By similarity

Kineticsi

  1. KM=0.6 µM for (2E,6E)-farnesyl diphosphate1 Publication

    Pathway: aristolochene biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes aristolochene from farnesyl diphosphate.
    Proteins known to be involved in this subpathway in this organism are:
    1. Aristolochene synthase (ARI1)
    This subpathway is part of the pathway aristolochene biosynthesis, which is itself part of Sesquiterpene biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes aristolochene from farnesyl diphosphate, the pathway aristolochene biosynthesis and in Sesquiterpene biosynthesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi115 – 1151Magnesium 1By similarity
    Metal bindingi115 – 1151Magnesium 2By similarity
    Binding sitei200 – 2001SubstrateBy similarity
    Metal bindingi244 – 2441Magnesium 3By similarity
    Metal bindingi248 – 2481Magnesium 3By similarity
    Binding sitei251 – 2511SubstrateBy similarity
    Metal bindingi252 – 2521Magnesium 3By similarity

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-16547.
    BRENDAi4.2.3.9. 4638.
    UniPathwayiUPA00177; UER00582.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aristolochene synthase (EC:4.2.3.9)
    Short name:
    AS
    Alternative name(s):
    Sesquiterpene cyclase
    Gene namesi
    Name:ARI1
    OrganismiPenicillium roqueforti
    Taxonomic identifieri5082 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaEurotiomycetesEurotiomycetidaeEurotialesAspergillaceaePenicillium

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi92 – 921Y → F: Causes 100-fold reduction in kcat but a 50-fold decrease in KM, resulting in a 2-fold decrease in catalytic efficiency. 1 Publication
    Mutagenesisi115 – 1151D → N: Abolishes catalytic activity. 1 Publication
    Mutagenesisi244 – 2441N → L: Abolishes catalytic activity. 1 Publication
    Mutagenesisi248 – 2481S → A: Abolishes catalytic activity; when associated with D-252. 1 Publication
    Mutagenesisi252 – 2521E → D: Abolishes catalytic activity; when associated with A-248. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 342342Aristolochene synthasePRO_0000064677Add
    BLAST

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    Secondary structure

    1
    342
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi54 – 6815Combined sources
    Helixi74 – 8310Combined sources
    Helixi85 – 928Combined sources
    Turni98 – 1003Combined sources
    Helixi101 – 12020Combined sources
    Helixi123 – 13715Combined sources
    Helixi148 – 18033Combined sources
    Turni181 – 1833Combined sources
    Helixi193 – 2019Combined sources
    Helixi204 – 21714Combined sources
    Helixi223 – 2275Combined sources
    Helixi230 – 24819Combined sources
    Turni249 – 2524Combined sources
    Helixi269 – 2779Combined sources
    Helixi281 – 30727Combined sources
    Helixi315 – 33622Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1DGPX-ray2.80A/B40-339[»]
    1DI1X-ray2.50A/B40-339[»]
    1F1Kmodel-A1-342[»]
    1F1Lmodel-A1-342[»]
    1F1Nmodel-A1-342[»]
    1F1Pmodel-A1-342[»]
    ProteinModelPortaliQ03471.
    SMRiQ03471. Positions 40-339.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ03471.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni340 – 3412Substrate-bindingBy similarity

    Sequence similaritiesi

    Belongs to the terpene synthase family.Curated

    Phylogenomic databases

    PhylomeDBiQ03471.

    Family and domain databases

    Gene3Di1.10.600.10. 1 hit.
    InterProiIPR008949. Isoprenoid_synthase_dom.
    IPR005630. Terpene_synthase_metal-bd.
    [Graphical view]
    PfamiPF03936. Terpene_synth_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF48576. SSF48576. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q03471-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MATSTETISS LAQPFVHLEN PINSPLVKET IRPRNDTTIT PPPTQWSYLC
    60 70 80 90 100
    HPRVKEVQDE VDGYFLENWK FPSFKAVRTF LDAKFSEVTC LYFPLALDDR
    110 120 130 140 150
    IHFACRLLTV LFLIDDVLEH MSFADGEAYN NRLIPISRGD VLPDRTKPEE
    160 170 180 190 200
    FILYDLWESM RAHDAELANE VLEPTFVFMR AQTDRARLSI HELGHYLEYR
    210 220 230 240 250
    EKDVGKALLS ALMRFSMGLR LSADELQDMK ALEANCAKQL SVVNDIYSYD
    260 270 280 290 300
    KEEEASRTGH KEGAFLCSAV KVLAEESKLG IPATKRVLWS MTREWETVHD
    310 320 330 340
    EIVAEKIASP DGCSEAAKAY MKGLEYQMSG NEQWSKTTRR YN
    Length:342
    Mass (Da):39,192
    Last modified:October 1, 1993 - v1
    Checksum:iACFBD63F4FF9BB03
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L05193 Genomic DNA. Translation: AAA33694.1.
    PIRiA45462.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L05193 Genomic DNA. Translation: AAA33694.1.
    PIRiA45462.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1DGPX-ray2.80A/B40-339[»]
    1DI1X-ray2.50A/B40-339[»]
    1F1Kmodel-A1-342[»]
    1F1Lmodel-A1-342[»]
    1F1Nmodel-A1-342[»]
    1F1Pmodel-A1-342[»]
    ProteinModelPortaliQ03471.
    SMRiQ03471. Positions 40-339.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Phylogenomic databases

    PhylomeDBiQ03471.

    Enzyme and pathway databases

    UniPathwayiUPA00177; UER00582.
    BioCyciMetaCyc:MONOMER-16547.
    BRENDAi4.2.3.9. 4638.

    Miscellaneous databases

    EvolutionaryTraceiQ03471.

    Family and domain databases

    Gene3Di1.10.600.10. 1 hit.
    InterProiIPR008949. Isoprenoid_synthase_dom.
    IPR005630. Terpene_synthase_metal-bd.
    [Graphical view]
    PfamiPF03936. Terpene_synth_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF48576. SSF48576. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    1. "Aristolochene synthase. Isolation, characterization, and bacterial expression of a sesquiterpenoid biosynthetic gene (Ari1) from Penicillium roqueforti."
      Proctor R.H., Hohn T.M.
      J. Biol. Chem. 268:4543-4548(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 56-70; 76-84; 245-251 AND 323-336, FUNCTION, CATALYTIC ACTIVITY.
      Strain: ATCC 10110 / CBS 221.30 / NBRC 5459 / NRRL 849.
    2. "Aristolochene synthase: mechanistic analysis of active site residues by site-directed mutagenesis."
      Felicetti B., Cane D.E.
      J. Am. Chem. Soc. 126:7212-7221(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-92; ASP-115; ASN-244; SER-248 AND GLU-252.
    3. "Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti."
      Caruthers J.M., Kang I., Rynkiewicz M.J., Cane D.E., Christianson D.W.
      J. Biol. Chem. 275:25533-25539(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).

    Entry informationi

    Entry nameiARIS_PENRO
    AccessioniPrimary (citable) accession number: Q03471
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: October 1, 1993
    Last modified: April 1, 2015
    This is version 91 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.