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Protein

Pentalenene synthase

Gene

penA

Organism
Streptomyces exfoliatus (Streptomyces hydrogenans)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the cyclization of farnesyl diphosphate (FPP) to the tricyclic sesquiterpene pentalenene, which is the hydrocarbon precursor of the pentalenolactone family of antibiotics produced by a variety of Streptomyces species.1 Publication

Catalytic activityi

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

Cofactori

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

Kineticsi

  1. KM=310 nM for FPP1 Publication

    pH dependencei

    Optimum pH is 8.2-8.4.1 Publication

    Pathway: pentalenene biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes pentalenene from farnesyl diphosphate.
    Proteins known to be involved in this subpathway in this organism are:
    1. Pentalenene synthase (penA)
    This subpathway is part of the pathway pentalenene 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 pentalenene from farnesyl diphosphate, the pathway pentalenene biosynthesis and in Sesquiterpene biosynthesis.

    Pathway: pentalenolactone biosynthesis

    This protein is involved in the pathway pentalenolactone biosynthesis, which is part of Antibiotic biosynthesis.
    View all proteins of this organism that are known to be involved in the pathway pentalenolactone biosynthesis and in Antibiotic biosynthesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi80 – 801Magnesium 1
    Metal bindingi80 – 801Magnesium 2
    Metal bindingi84 – 841Magnesium 1
    Metal bindingi84 – 841Magnesium 2
    Metal bindingi219 – 2191Magnesium 3
    Metal bindingi223 – 2231Magnesium 3By similarity
    Metal bindingi227 – 2271Magnesium 3By similarity

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    Antibiotic biosynthesis

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-16834.
    BRENDAi4.2.3.7. 22521.
    UniPathwayiUPA00171; UER00581.
    UPA00974.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pentalenene synthase (EC:4.2.3.7)
    Short name:
    PS
    Alternative name(s):
    Pentalenolactone biosynthesis protein A
    Sesquiterpene cyclase
    Sesquiterpene synthase
    Gene namesi
    Name:penA
    OrganismiStreptomyces exfoliatus (Streptomyces hydrogenans)
    Taxonomic identifieri1905 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaStreptomycetalesStreptomycetaceaeStreptomyces

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi76 – 761F → A: Loss of activity. 1 Publication
    Mutagenesisi77 – 771F → A: Loss of activity. 1 Publication
    Mutagenesisi77 – 771F → Y: 20-fold decrease in activity and catalytic efficiency. 1 Publication
    Mutagenesisi80 – 801D → E: 150-fold decrease in activity. 20-fold increase in Km for FPP. 1 Publication
    Mutagenesisi81 – 811D → E: 50-fold decrease in activity. 9-fold increase in Km for FPP. 1 Publication
    Mutagenesisi84 – 841D → E: 2.5-fold increase in activity. 7-fold increase in Km for FPP. 1 Publication
    Mutagenesisi219 – 2191N → A: Loss of activity. 1 Publication
    Mutagenesisi219 – 2191N → D: 60-fold decrease in activity. 55-fold increase in Km for FPP. 1 Publication
    Mutagenesisi219 – 2191N → L: Loss of activity. 1 Publication
    Mutagenesisi308 – 3092WH → FF: 12-fold decrease in activity. 25-fold decrease in catalytic efficiency. 1 Publication
    Mutagenesisi308 – 3081W → F: 4-fold decrease in activity. 2-fold decrease in catalytic efficiency. 1 Publication
    Mutagenesisi309 – 3091H → A: 3-fold decrease in activity. 2 Publications
    Mutagenesisi309 – 3091H → C: 4-fold decrease in activity. 2 Publications
    Mutagenesisi309 – 3091H → F: 17-fold decrease in activity. 5-fold increase in Km for FPP. 2 Publications
    Mutagenesisi309 – 3091H → S: 3-fold decrease in activity. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 337336Pentalenene synthasePRO_0000097092Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi128 ↔ 136

    Keywords - PTMi

    Disulfide bond

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Structurei

    Secondary structure

    1
    337
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi19 – 246Combined sources
    Helixi28 – 325Combined sources
    Helixi39 – 468Combined sources
    Helixi50 – 578Combined sources
    Helixi64 – 8118Combined sources
    Helixi86 – 894Combined sources
    Helixi91 – 10212Combined sources
    Helixi103 – 1053Combined sources
    Helixi115 – 12814Combined sources
    Helixi133 – 15422Combined sources
    Helixi166 – 17611Combined sources
    Helixi179 – 19012Combined sources
    Helixi196 – 1994Combined sources
    Helixi202 – 22221Combined sources
    Helixi224 – 2296Combined sources
    Helixi236 – 2449Combined sources
    Helixi248 – 27932Combined sources
    Helixi284 – 29613Combined sources
    Helixi298 – 30811Combined sources
    Turni309 – 3113Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1HM4X-ray3.47A/B2-337[»]
    1HM7X-ray2.90A/B2-337[»]
    1PS1X-ray2.60A/B1-337[»]
    ProteinModelPortaliQ55012.
    SMRiQ55012. Positions 7-311.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ55012.

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi80 – 845DDXXD motif

    Domaini

    The Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for the catalytic activity, presumably through binding to Mg2+.

    Sequence similaritiesi

    Belongs to the terpene synthase family.Curated

    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.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q55012-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPQDVDFHIP LPGRQSPDHA RAEAEQLAWP RSLGLIRSDA AAERHLRGGY
    60 70 80 90 100
    ADLASRFYPH ATGADLDLGV DLMSWFFLFD DLFDGPRGEN PEDTKQLTDQ
    110 120 130 140 150
    VAAALDGPLP DTAPPIAHGF ADIWRRTCEG MTPAWCARSA RHWRNYFDGY
    160 170 180 190 200
    VDEAESRFWN APCDSAAQYL AMRRHTIGVQ PTVDLAERAG RFEVPHRVFD
    210 220 230 240 250
    SAVMSAMLQI AVDVNLLLND IASLEKEEAR GEQNNMVMIL RREHGWSKSR
    260 270 280 290 300
    SVSHMQNEVR ARLEQYLLLE SCLPKVGEIY QLDTAEREAL ERYRTDAVRT
    310 320 330
    VIRGSYDWHR SSGRYDAEFA LAAGAQGYLE ELGSSAH
    Length:337
    Mass (Da):38,002
    Last modified:January 23, 2007 - v4
    Checksum:i417FCE6D8C4BB18C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti118 – 1181H → W AA sequence (PubMed:8180213).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U05213 Unassigned DNA. Translation: AAA19131.1.
    HQ292066 Genomic DNA. Translation: ADO85594.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U05213 Unassigned DNA. Translation: AAA19131.1.
    HQ292066 Genomic DNA. Translation: ADO85594.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1HM4X-ray3.47A/B2-337[»]
    1HM7X-ray2.90A/B2-337[»]
    1PS1X-ray2.60A/B1-337[»]
    ProteinModelPortaliQ55012.
    SMRiQ55012. Positions 7-311.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Enzyme and pathway databases

    UniPathwayiUPA00171; UER00581.
    UPA00974.
    BioCyciMetaCyc:MONOMER-16834.
    BRENDAi4.2.3.7. 22521.

    Miscellaneous databases

    EvolutionaryTraceiQ55012.

    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. "Pentalenene synthase. Purification, molecular cloning, sequencing, and high-level expression in Escherichia coli of a terpenoid cyclase from Streptomyces UC5319."
      Cane D.E., Sohng J.-K., Lamberson C.R., Rudnicki S.M., Wu Z., Lloyd M.D., Oliver J.S., Hubbard B.R.
      Biochemistry 33:5846-5857(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-28; 57-73; 96-120 AND 145-157, FUNCTION, SUBUNIT, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.
      Strain: UC5319.
    2. "Genome mining in streptomyces. Discovery of an unprecedented P450-catalyzed oxidative rearrangement that is the final step in the biosynthesis of pentalenolactone."
      Zhu D., Seo M.J., Ikeda H., Cane D.E.
      J. Am. Chem. Soc. 133:2128-2131(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: UC5319.
    3. "Pentalenene synthase. Histidine-309 is not required for catalytic activity."
      Seemann M., Zhai G., Umezawa K., Cane D.E.
      J. Am. Chem. Soc. 121:591-592(1999)
      Cited for: MUTAGENESIS OF HIS-309.
    4. "Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology."
      Lesburg C.A., Zhai G., Cane D.E., Christianson D.W.
      Science 277:1820-1824(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
    5. "Pentalenene synthase. Analysis of active site residues by site-directed mutagenesis."
      Seemann M., Zhai G., de Kraker J.-W., Paschall C.M., Christianson D.W., Cane D.E.
      J. Am. Chem. Soc. 124:7681-7689(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF MUTANT LEU-219, CATALYTIC ACTIVITY, MUTAGENESIS OF PHE-76; PHE-77; ASP-80; ASP-81; ASP-84; ASN-219; 308-TRP-HIS-309; TRP-308 AND HIS-309.

    Entry informationi

    Entry nameiPENA_STREX
    AccessioniPrimary (citable) accession number: Q55012
    Secondary accession number(s): E3VWK6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: January 23, 2007
    Last modified: June 24, 2015
    This is version 83 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    All the mutants (Ref. 3 and PubMed:12083921) retained substantial pentalenene synthase activity accompanied by production of varying proportions of abortive cyclization products such as germacrene A, protoilludene and beta-caryophyllene. This is a true derailment or diversion of the normal cyclization reaction, and not simply the consequence of trapping of a normally cryptic, cationic intermediate.

    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.