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Protein

4-hydroxy-3-methylbut-2-enyl diphosphate reductase

Gene

ispH

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

Functioni

Converts 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Is also involved in penicillin tolerance and control of the stringent response. Seems to directly or indirectly interact with RelA to maintain it in an inactive form during normal growth.3 Publications

Catalytic activityi

Isopentenyl diphosphate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+.2 Publications
Dimethylallyl diphosphate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+.2 Publications

Cofactori

[3Fe-4S] cluster3 PublicationsNote: Binds 1 [3Fe-4S] cluster per subunit.3 Publications

Enzyme regulationi

Addition of Ca2+, Mg2+, Mn2+, Ni2+, Co2+ or Fe2+ decreases the activity. Addition of Zn2+ results in complete loss of activity.1 Publication

Kineticsi

  1. KM=30 µM for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate1 Publication

    pH dependencei

    Optimum pH is 7.0.

    Pathwayi: dimethylallyl diphosphate biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes dimethylallyl diphosphate from (2E)-4-hydroxy-3-methylbutenyl diphosphate.
    Proteins known to be involved in this subpathway in this organism are:
    1. 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (ispH)
    This subpathway is part of the pathway dimethylallyl diphosphate biosynthesis, which is itself part of Isoprenoid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes dimethylallyl diphosphate from (2E)-4-hydroxy-3-methylbutenyl diphosphate, the pathway dimethylallyl diphosphate biosynthesis and in Isoprenoid biosynthesis.

    Pathwayi: isopentenyl diphosphate biosynthesis via DXP pathway

    This protein is involved in step 6 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 bindingi12Iron-sulfur (3Fe-4S)2 Publications1
    Binding sitei41Substrate2 Publications1
    Binding sitei74Substrate2 Publications1
    Metal bindingi96Iron-sulfur (3Fe-4S)2 Publications1
    Binding sitei124Substrate2 Publications1
    Binding sitei167Substrate2 Publications1
    Metal bindingi197Iron-sulfur (3Fe-4S)2 Publications1
    Binding sitei269Substrate2 Publications1

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Isoprene biosynthesis

    Keywords - Ligandi

    3Fe-4S, Iron, Iron-sulfur, Metal-binding, NADP

    Enzyme and pathway databases

    BioCyciEcoCyc:EG11081-MONOMER.
    ECOL316407:JW0027-MONOMER.
    MetaCyc:EG11081-MONOMER.
    UniPathwayiUPA00056; UER00097.
    UPA00059; UER00105.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    4-hydroxy-3-methylbut-2-enyl diphosphate reductase (EC:1.17.7.42 Publications)
    Gene namesi
    Name:ispH
    Synonyms:lytB, yaaE
    Ordered Locus Names:b0029, JW0027
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG11081. ispH.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: EcoCyc
    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi12C → S: Loss of activity. 2 Publications1
    Mutagenesisi41H → N: No effect on the activity. 1 Publication1
    Mutagenesisi74H → N: Reduces activity 2-fold. 1 Publication1
    Mutagenesisi96C → S: Loss of activity. 2 Publications1
    Mutagenesisi99V → A: No effect on the activity. 1 Publication1
    Mutagenesisi124H → N: Reduces activity 100-fold. 1 Publication1
    Mutagenesisi126E → D or Q: Reduces activity 100-fold. 2 Publications1
    Mutagenesisi167T → C: Reduces activity 3-fold. 2 Publications1
    Mutagenesisi167T → S: No effect on the activity. 2 Publications1
    Mutagenesisi197C → S: Loss of activity. 2 Publications1
    Mutagenesisi225S → C: Reduces activity 100-fold. 1 Publication1
    Mutagenesisi227N → Q: Reduces activity 20-fold. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001288121 – 3164-hydroxy-3-methylbut-2-enyl diphosphate reductaseAdd BLAST316

    Proteomic databases

    EPDiP62623.
    PaxDbiP62623.
    PRIDEiP62623.

    Interactioni

    Subunit structurei

    Homodimer.4 Publications

    Protein-protein interaction databases

    BioGridi4262917. 321 interactors.
    DIPiDIP-35808N.
    IntActiP62623. 7 interactors.
    STRINGi511145.b0029.

    Structurei

    Secondary structure

    1316
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi2 – 5Combined sources4
    Helixi13 – 29Combined sources17
    Beta strandi33 – 37Combined sources5
    Beta strandi39 – 41Combined sources3
    Helixi43 – 51Combined sources9
    Beta strandi54 – 59Combined sources6
    Helixi60 – 62Combined sources3
    Beta strandi68 – 71Combined sources4
    Helixi78 – 86Combined sources9
    Beta strandi90 – 93Combined sources4
    Helixi97 – 112Combined sources16
    Beta strandi115 – 120Combined sources6
    Helixi125 – 131Combined sources7
    Beta strandi137 – 139Combined sources3
    Beta strandi141 – 144Combined sources4
    Helixi147 – 152Combined sources6
    Beta strandi160 – 165Combined sources6
    Beta strandi167 – 169Combined sources3
    Helixi171 – 184Combined sources14
    Beta strandi191 – 193Combined sources3
    Helixi198 – 213Combined sources16
    Beta strandi215 – 220Combined sources6
    Helixi226 – 237Combined sources12
    Beta strandi241 – 247Combined sources7
    Helixi248 – 250Combined sources3
    Helixi253 – 255Combined sources3
    Turni256 – 258Combined sources3
    Beta strandi260 – 266Combined sources7
    Helixi272 – 284Combined sources13
    Beta strandi289 – 292Combined sources4
    Beta strandi300 – 302Combined sources3
    Helixi306 – 308Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3F7TX-ray1.80A/B1-316[»]
    3KE8X-ray1.70A/B1-316[»]
    3KE9X-ray1.90A/B1-316[»]
    3KEFX-ray1.70A/B1-316[»]
    3KELX-ray1.80A/B1-316[»]
    3KEMX-ray2.00A/B1-316[»]
    3SZLX-ray1.60A/B1-316[»]
    3SZOX-ray1.60A/B1-316[»]
    3SZUX-ray1.40A/B1-316[»]
    3T0FX-ray1.90A/B1-316[»]
    3T0GX-ray2.10A/B1-316[»]
    3URKX-ray1.50A/B1-316[»]
    3UTCX-ray1.90A/B1-316[»]
    3UTDX-ray1.70A/B1-316[»]
    3UV3X-ray1.60A/B1-316[»]
    3UV6X-ray1.70A/B1-316[»]
    3UV7X-ray1.60A/B1-316[»]
    3UWMX-ray1.80A/B1-316[»]
    3ZGLX-ray1.68A/B1-316[»]
    3ZGNX-ray1.95A/B1-316[»]
    4EB3X-ray1.90A/B1-315[»]
    4H4CX-ray1.80A/B1-315[»]
    4H4DX-ray1.35A/B1-315[»]
    4H4EX-ray1.70A/B1-315[»]
    ProteinModelPortaliP62623.
    SMRiP62623.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP62623.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni225 – 227Substrate binding3

    Sequence similaritiesi

    Belongs to the IspH family.Curated

    Phylogenomic databases

    eggNOGiENOG4105C48. Bacteria.
    COG0761. LUCA.
    HOGENOMiHOG000220192.
    InParanoidiP62623.
    KOiK03527.
    OMAiDDLTFMT.
    PhylomeDBiP62623.

    Family and domain databases

    CDDicd13944. lytB_ispH. 1 hit.
    HAMAPiMF_00191. IspH. 1 hit.
    InterProiIPR003451. LytB/IspH.
    [Graphical view]
    PfamiPF02401. LYTB. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00216. ispH_lytB. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P62623-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MQILLANPRG FCAGVDRAIS IVENALAIYG APIYVRHEVV HNRYVVDSLR
    60 70 80 90 100
    ERGAIFIEQI SEVPDGAILI FSAHGVSQAV RNEAKSRDLT VFDATCPLVT
    110 120 130 140 150
    KVHMEVARAS RRGEESILIG HAGHPEVEGT MGQYSNPEGG MYLVESPDDV
    160 170 180 190 200
    WKLTVKNEEK LSFMTQTTLS VDDTSDVIDA LRKRFPKIVG PRKDDICYAT
    210 220 230 240 250
    TNRQEAVRAL AEQAEVVLVV GSKNSSNSNR LAELAQRMGK RAFLIDDAKD
    260 270 280 290 300
    IQEEWVKEVK CVGVTAGASA PDILVQNVVA RLQQLGGGEA IPLEGREENI
    310
    VFEVPKELRV DIREVD
    Length:316
    Mass (Da):34,775
    Last modified:July 19, 2004 - v1
    Checksum:i0E7B378BD49AB771
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY062212 Genomic DNA. Translation: AAL38655.1.
    X54945 Genomic DNA. Translation: CAA38707.1.
    U00096 Genomic DNA. Translation: AAC73140.1.
    AP009048 Genomic DNA. Translation: BAB96598.1.
    PIRiJE0403.
    RefSeqiNP_414570.1. NC_000913.3.
    WP_001166395.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC73140; AAC73140; b0029.
    BAB96598; BAB96598; BAB96598.
    GeneIDi944777.
    KEGGiecj:JW0027.
    eco:b0029.
    PATRICi32115149. VBIEscCol129921_0026.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY062212 Genomic DNA. Translation: AAL38655.1.
    X54945 Genomic DNA. Translation: CAA38707.1.
    U00096 Genomic DNA. Translation: AAC73140.1.
    AP009048 Genomic DNA. Translation: BAB96598.1.
    PIRiJE0403.
    RefSeqiNP_414570.1. NC_000913.3.
    WP_001166395.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3F7TX-ray1.80A/B1-316[»]
    3KE8X-ray1.70A/B1-316[»]
    3KE9X-ray1.90A/B1-316[»]
    3KEFX-ray1.70A/B1-316[»]
    3KELX-ray1.80A/B1-316[»]
    3KEMX-ray2.00A/B1-316[»]
    3SZLX-ray1.60A/B1-316[»]
    3SZOX-ray1.60A/B1-316[»]
    3SZUX-ray1.40A/B1-316[»]
    3T0FX-ray1.90A/B1-316[»]
    3T0GX-ray2.10A/B1-316[»]
    3URKX-ray1.50A/B1-316[»]
    3UTCX-ray1.90A/B1-316[»]
    3UTDX-ray1.70A/B1-316[»]
    3UV3X-ray1.60A/B1-316[»]
    3UV6X-ray1.70A/B1-316[»]
    3UV7X-ray1.60A/B1-316[»]
    3UWMX-ray1.80A/B1-316[»]
    3ZGLX-ray1.68A/B1-316[»]
    3ZGNX-ray1.95A/B1-316[»]
    4EB3X-ray1.90A/B1-315[»]
    4H4CX-ray1.80A/B1-315[»]
    4H4DX-ray1.35A/B1-315[»]
    4H4EX-ray1.70A/B1-315[»]
    ProteinModelPortaliP62623.
    SMRiP62623.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4262917. 321 interactors.
    DIPiDIP-35808N.
    IntActiP62623. 7 interactors.
    STRINGi511145.b0029.

    Proteomic databases

    EPDiP62623.
    PaxDbiP62623.
    PRIDEiP62623.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC73140; AAC73140; b0029.
    BAB96598; BAB96598; BAB96598.
    GeneIDi944777.
    KEGGiecj:JW0027.
    eco:b0029.
    PATRICi32115149. VBIEscCol129921_0026.

    Organism-specific databases

    EchoBASEiEB1073.
    EcoGeneiEG11081. ispH.

    Phylogenomic databases

    eggNOGiENOG4105C48. Bacteria.
    COG0761. LUCA.
    HOGENOMiHOG000220192.
    InParanoidiP62623.
    KOiK03527.
    OMAiDDLTFMT.
    PhylomeDBiP62623.

    Enzyme and pathway databases

    UniPathwayiUPA00056; UER00097.
    UPA00059; UER00105.
    BioCyciEcoCyc:EG11081-MONOMER.
    ECOL316407:JW0027-MONOMER.
    MetaCyc:EG11081-MONOMER.

    Miscellaneous databases

    EvolutionaryTraceiP62623.
    PROiP62623.

    Family and domain databases

    CDDicd13944. lytB_ispH. 1 hit.
    HAMAPiMF_00191. IspH. 1 hit.
    InterProiIPR003451. LytB/IspH.
    [Graphical view]
    PfamiPF02401. LYTB. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00216. ispH_lytB. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiISPH_ECOLI
    AccessioniPrimary (citable) accession number: P62623
    Secondary accession number(s): P22565
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: July 19, 2004
    Last modified: November 2, 2016
    This is version 107 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    PubMed:12706830 and PubMed:22137895 authors have reported the presence of a 4Fe-4S iron-sulfur cluster. It could be due to experimental conditions.

    Keywords - Technical termi

    3D-structure, Complete proteome, 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.