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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)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi8 – 81Divalent metal cation
    Metal bindingi10 – 101Divalent metal cation
    Sitei34 – 341Transition state stabilizer
    Metal bindingi42 – 421Divalent metal cation
    Binding sitei65 – 651Substrate; via carbonyl oxygen
    Sitei133 – 1331Transition state stabilizer
    Binding sitei139 – 1391Substrate; via carbonyl oxygen
    Binding sitei142 – 1421Substrate

    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 lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    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)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi8 – 81D → S: Loss of activity. 1 Publication
    Mutagenesisi42 – 421H → S: Loss of activity. 1 Publication
    Mutagenesisi56 – 561D → S: 35% decrease of activity. 1 Publication
    Mutagenesisi142 – 1421R → M: Little effect on the overall structure; when associated with L-144. 1 Publication
    Mutagenesisi144 – 1441E → L: Little effect on the overall structure; when associated with M-142. 1 Publication

    Chemistry

    ChEMBLiCHEMBL3217375.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 1591592-C-methyl-D-erythritol 2,4-cyclodiphosphate synthasePRO_0000189464Add
    BLAST

    Proteomic databases

    PaxDbiP62617.

    Interactioni

    Subunit structurei

    Homotrimer.7 Publications

    GO - Molecular functioni

    • identical protein binding Source: EcoCyc

    Protein-protein interaction databases

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

    Chemistry

    BindingDBiP62617.

    Structurei

    Secondary structure

    159
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi1 – 1616Combined sources
    Beta strandi18 – 203Combined sources
    Beta strandi23 – 253Combined sources
    Beta strandi28 – 314Combined sources
    Beta strandi33 – 353Combined sources
    Helixi39 – 5113Combined sources
    Helixi57 – 604Combined sources
    Beta strandi63 – 653Combined sources
    Helixi66 – 683Combined sources
    Beta strandi69 – 713Combined sources
    Helixi73 – 8614Combined sources
    Beta strandi90 – 9910Combined sources
    Beta strandi101 – 1033Combined sources
    Helixi106 – 1083Combined sources
    Helixi109 – 11911Combined sources
    Helixi124 – 1263Combined sources
    Beta strandi127 – 1326Combined sources
    Helixi138 – 1414Combined sources
    Beta strandi144 – 15512Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    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. Positions 1-156.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP62617.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni8 – 103Substrate binding
    Regioni34 – 352Substrate binding
    Regioni38 – 469Substrate binding
    Regioni56 – 583Substrate binding
    Regioni61 – 655Substrate binding
    Regioni100 – 1067Substrate binding
    Regioni131 – 1355Substrate binding

    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
    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. Positions 1-156.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

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

    Chemistry

    BindingDBiP62617.
    ChEMBLiCHEMBL3217375.

    Proteomic databases

    PaxDbiP62617.

    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: September 7, 2016
    This is version 119 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.