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Protein

2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase

Gene

ispF

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP). Also converts 4-diphosphocytidyl-2-C-methyl-D-erythritol into 2-C-methyl-D-erythritol 3,4-cyclophosphate and CMP.2 Publications

Catalytic activityi

2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate + CMP.2 Publications

Cofactori

a divalent metal cation8 PublicationsNote: Binds 1 divalent metal cation per subunit.8 Publications

Enzyme regulationi

Activated by 2C-methyl-D-erythritol 4-phosphate (MEP).1 Publication

Kineticsi

kcat is 61 min(-1) for CDP-ME2P (at pH 7.4).

  1. KM=339 µM for CDP-ME2P (at pH 7.4)1 Publication

    Pathwayi: isopentenyl diphosphate biosynthesis via DXP pathway

    This protein is involved in step 4 of the subpathway that synthesizes isopentenyl diphosphate from 1-deoxy-D-xylulose 5-phosphate.
    Proteins known to be involved in the 6 steps of the subpathway in this organism are:
    1. 1-deoxy-D-xylulose 5-phosphate reductoisomerase (dxr)
    2. 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (ispD)
    3. 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (ispE)
    4. 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (ispF)
    5. 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) (ispG)
    6. 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (ispH)
    This subpathway is part of the pathway isopentenyl diphosphate biosynthesis via DXP pathway, which is itself part of Isoprenoid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes isopentenyl diphosphate from 1-deoxy-D-xylulose 5-phosphate, the pathway isopentenyl diphosphate biosynthesis via DXP pathway and in Isoprenoid biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi8Divalent metal cation1
    Metal bindingi10Divalent metal cation1
    Sitei34Transition state stabilizer1
    Metal bindingi42Divalent metal cation1
    Binding sitei65Substrate; via carbonyl oxygen1
    Sitei133Transition state stabilizer1
    Binding sitei139Substrate; via carbonyl oxygen1
    Binding sitei142Substrate1

    GO - Molecular functioni

    • 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity Source: EcoCyc
    • identical protein binding Source: EcoCyc
    • manganese ion binding Source: EcoCyc
    • metal ion binding Source: EcoCyc
    • zinc ion binding Source: EcoCyc

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    Isoprene biosynthesis

    Keywords - Ligandi

    Metal-binding

    Enzyme and pathway databases

    BioCyciEcoCyc:EG11816-MONOMER.
    ECOL316407:JW2716-MONOMER.
    MetaCyc:EG11816-MONOMER.
    BRENDAi4.6.1.12. 2026.
    UniPathwayiUPA00056; UER00095.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (EC:4.6.1.12)
    Short name:
    MECDP-synthase
    Short name:
    MECPP-synthase
    Short name:
    MECPS
    Gene namesi
    Name:ispF
    Synonyms:mecS, ygbB
    Ordered Locus Names:b2746, JW2716
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG11816. ispF.

    Pathology & Biotechi

    Disruption phenotypei

    Cells lacking this gene reveal a filamentous phenotype.1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi8D → S: Loss of activity. 1 Publication1
    Mutagenesisi42H → S: Loss of activity. 1 Publication1
    Mutagenesisi56D → S: 35% decrease of activity. 1 Publication1
    Mutagenesisi142R → M: Little effect on the overall structure; when associated with L-144. 1 Publication1
    Mutagenesisi144E → L: Little effect on the overall structure; when associated with M-142. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL3217375.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001894641 – 1592-C-methyl-D-erythritol 2,4-cyclodiphosphate synthaseAdd BLAST159

    Proteomic databases

    PaxDbiP62617.
    PRIDEiP62617.

    Interactioni

    Subunit structurei

    Homotrimer.7 Publications

    GO - Molecular functioni

    • identical protein binding Source: EcoCyc

    Protein-protein interaction databases

    BioGridi4262279. 275 interactors.
    DIPiDIP-48029N.
    IntActiP62617. 7 interactors.
    STRINGi511145.b2746.

    Chemistry databases

    BindingDBiP62617.

    Structurei

    Secondary structure

    1159
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi1 – 16Combined sources16
    Beta strandi18 – 20Combined sources3
    Beta strandi23 – 25Combined sources3
    Beta strandi28 – 31Combined sources4
    Beta strandi33 – 35Combined sources3
    Helixi39 – 51Combined sources13
    Helixi57 – 60Combined sources4
    Beta strandi63 – 65Combined sources3
    Helixi66 – 68Combined sources3
    Beta strandi69 – 71Combined sources3
    Helixi73 – 86Combined sources14
    Beta strandi90 – 99Combined sources10
    Beta strandi101 – 103Combined sources3
    Helixi106 – 108Combined sources3
    Helixi109 – 119Combined sources11
    Helixi124 – 126Combined sources3
    Beta strandi127 – 132Combined sources6
    Helixi138 – 141Combined sources4
    Beta strandi144 – 155Combined sources12

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1GX1X-ray1.80A/B/C1-159[»]
    1H47X-ray2.00A/B/C/D/E/F1-159[»]
    1H48X-ray2.30A/B/C/D/E/F1-159[»]
    1JY8X-ray2.50A1-159[»]
    1KNJX-ray2.80A1-159[»]
    1KNKX-ray2.80A1-159[»]
    1U3LX-ray2.50A1-159[»]
    1U3PX-ray2.85A1-159[»]
    1U40X-ray2.80A1-159[»]
    1U43X-ray3.20A1-159[»]
    1YQNX-ray3.11A1-159[»]
    2AMTX-ray2.30A/B/C/D/E/F1-159[»]
    2GZLX-ray2.50A1-157[»]
    3ELCX-ray2.50A/B/C1-159[»]
    3EORX-ray2.90A1-159[»]
    3ERNX-ray2.10A/B/C/D/E/F1-159[»]
    3ESJX-ray2.70A1-159[»]
    3FBAX-ray3.10A1-159[»]
    ProteinModelPortaliP62617.
    SMRiP62617.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP62617.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni8 – 10Substrate binding3
    Regioni34 – 35Substrate binding2
    Regioni38 – 46Substrate binding9
    Regioni56 – 58Substrate binding3
    Regioni61 – 65Substrate binding5
    Regioni100 – 106Substrate binding7
    Regioni131 – 135Substrate binding5

    Sequence similaritiesi

    Belongs to the IspF family.Curated

    Phylogenomic databases

    eggNOGiENOG4108UH8. Bacteria.
    COG0245. LUCA.
    HOGENOMiHOG000239175.
    InParanoidiP62617.
    KOiK01770.
    OMAiIRIGNGY.
    PhylomeDBiP62617.

    Family and domain databases

    CDDicd00554. MECDP_synthase. 1 hit.
    Gene3Di3.30.1330.50. 1 hit.
    HAMAPiMF_00107. IspF. 1 hit.
    InterProiIPR003526. MECDP_synthase.
    IPR020555. MECDP_synthase_CS.
    [Graphical view]
    PfamiPF02542. YgbB. 1 hit.
    [Graphical view]
    SUPFAMiSSF69765. SSF69765. 1 hit.
    TIGRFAMsiTIGR00151. ispF. 1 hit.
    PROSITEiPS01350. ISPF. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P62617-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MRIGHGFDVH AFGGEGPIII GGVRIPYEKG LLAHSDGDVA LHALTDALLG
    60 70 80 90 100
    AAALGDIGKL FPDTDPAFKG ADSRELLREA WRRIQAKGYT LGNVDVTIIA
    110 120 130 140 150
    QAPKMLPHIP QMRVFIAEDL GCHMDDVNVK ATTTEKLGFT GRGEGIACEA

    VALLIKATK
    Length:159
    Mass (Da):16,898
    Last modified:July 19, 2004 - v1
    Checksum:i9FC5563623A62939
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L07942 Genomic DNA. Translation: AAA79837.1.
    AF230738 Genomic DNA. Translation: AAF44656.1.
    AB038256 Genomic DNA. Translation: BAA95145.1.
    U29579 Genomic DNA. Translation: AAA69256.1.
    U00096 Genomic DNA. Translation: AAC75788.1.
    AP009048 Genomic DNA. Translation: BAE76823.1.
    PIRiI55083.
    RefSeqiNP_417226.1. NC_000913.3.
    WP_001219242.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC75788; AAC75788; b2746.
    BAE76823; BAE76823; BAE76823.
    GeneIDi945057.
    KEGGiecj:JW2716.
    eco:b2746.
    PATRICi32120898. VBIEscCol129921_2841.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L07942 Genomic DNA. Translation: AAA79837.1.
    AF230738 Genomic DNA. Translation: AAF44656.1.
    AB038256 Genomic DNA. Translation: BAA95145.1.
    U29579 Genomic DNA. Translation: AAA69256.1.
    U00096 Genomic DNA. Translation: AAC75788.1.
    AP009048 Genomic DNA. Translation: BAE76823.1.
    PIRiI55083.
    RefSeqiNP_417226.1. NC_000913.3.
    WP_001219242.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1GX1X-ray1.80A/B/C1-159[»]
    1H47X-ray2.00A/B/C/D/E/F1-159[»]
    1H48X-ray2.30A/B/C/D/E/F1-159[»]
    1JY8X-ray2.50A1-159[»]
    1KNJX-ray2.80A1-159[»]
    1KNKX-ray2.80A1-159[»]
    1U3LX-ray2.50A1-159[»]
    1U3PX-ray2.85A1-159[»]
    1U40X-ray2.80A1-159[»]
    1U43X-ray3.20A1-159[»]
    1YQNX-ray3.11A1-159[»]
    2AMTX-ray2.30A/B/C/D/E/F1-159[»]
    2GZLX-ray2.50A1-157[»]
    3ELCX-ray2.50A/B/C1-159[»]
    3EORX-ray2.90A1-159[»]
    3ERNX-ray2.10A/B/C/D/E/F1-159[»]
    3ESJX-ray2.70A1-159[»]
    3FBAX-ray3.10A1-159[»]
    ProteinModelPortaliP62617.
    SMRiP62617.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4262279. 275 interactors.
    DIPiDIP-48029N.
    IntActiP62617. 7 interactors.
    STRINGi511145.b2746.

    Chemistry databases

    BindingDBiP62617.
    ChEMBLiCHEMBL3217375.

    Proteomic databases

    PaxDbiP62617.
    PRIDEiP62617.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC75788; AAC75788; b2746.
    BAE76823; BAE76823; BAE76823.
    GeneIDi945057.
    KEGGiecj:JW2716.
    eco:b2746.
    PATRICi32120898. VBIEscCol129921_2841.

    Organism-specific databases

    EchoBASEiEB1763.
    EcoGeneiEG11816. ispF.

    Phylogenomic databases

    eggNOGiENOG4108UH8. Bacteria.
    COG0245. LUCA.
    HOGENOMiHOG000239175.
    InParanoidiP62617.
    KOiK01770.
    OMAiIRIGNGY.
    PhylomeDBiP62617.

    Enzyme and pathway databases

    UniPathwayiUPA00056; UER00095.
    BioCyciEcoCyc:EG11816-MONOMER.
    ECOL316407:JW2716-MONOMER.
    MetaCyc:EG11816-MONOMER.
    BRENDAi4.6.1.12. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP62617.
    PROiP62617.

    Family and domain databases

    CDDicd00554. MECDP_synthase. 1 hit.
    Gene3Di3.30.1330.50. 1 hit.
    HAMAPiMF_00107. IspF. 1 hit.
    InterProiIPR003526. MECDP_synthase.
    IPR020555. MECDP_synthase_CS.
    [Graphical view]
    PfamiPF02542. YgbB. 1 hit.
    [Graphical view]
    SUPFAMiSSF69765. SSF69765. 1 hit.
    TIGRFAMsiTIGR00151. ispF. 1 hit.
    PROSITEiPS01350. ISPF. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiISPF_ECOLI
    AccessioniPrimary (citable) accession number: P62617
    Secondary accession number(s): P36663, Q2MA83
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: July 19, 2004
    Last modified: November 2, 2016
    This is version 121 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. 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.