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Protein

Aristolochene synthase

Gene

prx2

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

Functioni

Aristolochene synthase; part of the gene cluster that mediates the biosynthesis of PR-toxin, a bicyclic sesquiterpene belonging to the eremophilane class and acting as a mycotoxin (PubMed:24239699, PubMed:26274339). The first step of the pathway is catalyzed by the aristolochene synthase which performs the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene (PubMed:8440737, PubMed:15186158, PubMed:24239699). Following the formation of aristolochene, the non-oxygenated aristolochene is converted to the trioxygenated intermediate eremofortin B (PubMed:24239699). This conversion appears to involve three enzymes, a hydroxysterol oxidase-like enzyme, the quinone-oxidase prx3 that forms the quinone-type-structure in the bicyclic nucleus of aristolochene with the C8-oxo group and the C-3 hydroxyl group, and a P450 monooxygenase that introduces the epoxide at the double bond between carbons 1 and 2 (PubMed:24239699). No monoxy or dioxy-intermediates have been reported to be released to the broth, so these three early oxidative reactions may be coupled together (PubMed:24239699). Eremofortin B is further oxidized by another P450 monooxygenase, that introduces a second epoxide between carbons 7 and 11 prior to acetylation to eremofortin A (PubMed:24239699, PubMed:16345540). The second epoxidation may be performed by a second P450 monooxygenase (PubMed:24239699). After the acetylation step, the conversion of eremofortin A to eremofortin C and then to PR-toxin requires only two enzymes (PubMed:24239699). First the conversion of eremofortin A to eremofortin C proceeds by oxidation of the side chain of the molecule at C-12 and is catalyzed by the short-chain oxidoreductase prx1 (PubMed:24239699, PubMed:16345540). The primary alcohol formed by this reaction at C-12 is finally oxidized by the short-chain alcohol dehydrogenase prx4 that forms PR-toxin (PubMed:24239699, PubMed:16345540).5 Publications

Catalytic activityi

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

Cofactori

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

Kineticsi

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

    Pathwayi: 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 (prx2)
    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)DescriptionActionsGraphical viewLength
    Binding sitei92SubstrateCombined sources1 Publication1
    Binding sitei112SubstrateCombined sources1 Publication1
    Metal bindingi115Magnesium 1By similarity1
    Metal bindingi115Magnesium 2By similarity1
    Binding sitei178SubstrateCombined sources1 Publication1
    Binding sitei200SubstrateBy similarity1
    Metal bindingi244Magnesium 3By similarity1
    Binding sitei244SubstrateCombined sources1 Publication1
    Binding sitei245SubstrateCombined sources1 Publication1
    Metal bindingi248Magnesium 3By similarity1
    Binding sitei251SubstrateBy similarity1
    Metal bindingi252Magnesium 3By similarity1
    Sitei334Important for catalytic activityCombined sources1 Publication1

    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 synthase1 Publication (EC:4.2.3.92 Publications)
    Short name:
    AS1 Publication
    Alternative name(s):
    PR-toxin biosynthesis protein 21 Publication
    Sesquiterpene cyclase1 Publication
    Gene namesi
    Name:prx21 Publication
    Synonyms:ari11 Publication
    OrganismiPenicillium roqueforti
    Taxonomic identifieri5082 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaEurotiomycetesEurotiomycetidaeEurotialesAspergillaceaePenicillium

    Pathology & Biotechi

    Disruption phenotypei

    Reduces the production of PR-toxin and leads to a large increase in mycophenolic acid production (PubMed:24239699).1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi92Y → F: Causes 100-fold reduction in kcat but a 50-fold decrease in KM, resulting in a 2-fold decrease in catalytic efficiency. 1 Publication1
    Mutagenesisi115D → N: Abolishes catalytic activity. 1 Publication1
    Mutagenesisi244N → L: Abolishes catalytic activity. 1 Publication1
    Mutagenesisi248S → A: Abolishes catalytic activity; when associated with D-252. 1 Publication1
    Mutagenesisi252E → D: Abolishes catalytic activity; when associated with A-248. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000646771 – 342Aristolochene synthaseAdd BLAST342

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    Secondary structure

    1342
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi54 – 68Combined sources15
    Helixi74 – 83Combined sources10
    Helixi85 – 92Combined sources8
    Turni98 – 100Combined sources3
    Helixi101 – 120Combined sources20
    Helixi123 – 137Combined sources15
    Helixi148 – 180Combined sources33
    Turni181 – 183Combined sources3
    Helixi193 – 201Combined sources9
    Helixi204 – 217Combined sources14
    Helixi223 – 227Combined sources5
    Helixi230 – 248Combined sources19
    Turni249 – 252Combined sources4
    Helixi269 – 277Combined sources9
    Helixi281 – 307Combined sources27
    Helixi315 – 336Combined sources22

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ03471.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the terpene synthase family.Curated

    Phylogenomic databases

    KOiK14180.
    PhylomeDBiQ03471.

    Family and domain databases

    Gene3Di1.10.600.10. 1 hit.
    InterProiIPR008949. Isoprenoid_synthase_dom.
    [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.

    Genome annotation databases

    KEGGiag:AAA33694.

    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
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    KEGGiag:AAA33694.

    Phylogenomic databases

    KOiK14180.
    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.
    [Graphical view]
    SUPFAMiSSF48576. SSF48576. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPRX2_PENRO
    AccessioniPrimary (citable) accession number: Q03471
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: October 1, 1993
    Last modified: November 30, 2016
    This is version 100 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

    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 one 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.