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P62623

- ISPH_ECOLI

UniProt

P62623 - ISPH_ECOLI

Protein

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

Gene

ispH

Organism
Escherichia coli (strain K12)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 91 (01 Oct 2014)
      Sequence version 1 (19 Jul 2004)
      Previous versions | rss
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    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 + NAD(P)+ + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H.
    Dimethylallyl diphosphate + NAD(P)+ + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H.

    Cofactori

    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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi12 – 121Iron-sulfur (3Fe-4S)2 Publications
    Binding sitei41 – 411Substrate2 Publications
    Binding sitei74 – 741Substrate2 Publications
    Metal bindingi96 – 961Iron-sulfur (3Fe-4S)2 Publications
    Binding sitei124 – 1241Substrate2 Publications
    Binding sitei167 – 1671Substrate2 Publications
    Metal bindingi197 – 1971Iron-sulfur (3Fe-4S)2 Publications
    Binding sitei269 – 2691Substrate2 Publications

    GO - Molecular functioni

    1. 3 iron, 4 sulfur cluster binding Source: UniProtKB-HAMAP
    2. 4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase activity Source: UniProtKB-HAMAP
    3. hydroxymethylbutenyl pyrophosphate reductase activity Source: EcoCyc
    4. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. dimethylallyl diphosphate biosynthetic process Source: UniProtKB-UniPathway
    2. isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway Source: UniProtKB-HAMAP
    3. response to antibiotic Source: EcoCyc
    4. terpenoid biosynthetic process Source: UniProtKB-HAMAP
    5. ubiquinone biosynthetic process Source: EcoCyc

    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.
    BRENDAi1.17.1.2. 2026.
    UniPathwayiUPA00056; UER00097.
    UPA00059; UER00105.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    4-hydroxy-3-methylbut-2-enyl diphosphate reductase (EC:1.17.1.2)
    Gene namesi
    Name:ispH
    Synonyms:lytB, yaaE
    Ordered Locus Names:b0029, JW0027
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318: Chromosome, UP000000625: Chromosome

    Organism-specific databases

    EcoGeneiEG11081. ispH.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi12 – 121C → S: Loss of activity. 2 Publications
    Mutagenesisi41 – 411H → N: No effect on the activity. 1 Publication
    Mutagenesisi74 – 741H → N: Reduces activity 2-fold. 1 Publication
    Mutagenesisi96 – 961C → S: Loss of activity. 2 Publications
    Mutagenesisi99 – 991V → A: No effect on the activity. 1 Publication
    Mutagenesisi124 – 1241H → N: Reduces activity 100-fold. 1 Publication
    Mutagenesisi126 – 1261E → D or Q: Reduces activity 100-fold. 2 Publications
    Mutagenesisi167 – 1671T → C: Reduces activity 3-fold. 2 Publications
    Mutagenesisi167 – 1671T → S: No effect on the activity. 2 Publications
    Mutagenesisi197 – 1971C → S: Loss of activity. 2 Publications
    Mutagenesisi225 – 2251S → C: Reduces activity 100-fold. 1 Publication
    Mutagenesisi227 – 2271N → Q: Reduces activity 20-fold. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 3163164-hydroxy-3-methylbut-2-enyl diphosphate reductasePRO_0000128812Add
    BLAST

    Proteomic databases

    PaxDbiP62623.
    PRIDEiP62623.

    Expressioni

    Gene expression databases

    GenevestigatoriP62623.

    Interactioni

    Subunit structurei

    Homodimer.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    dnaKP0A6Y81EBI-554022,EBI-542092

    Protein-protein interaction databases

    DIPiDIP-35808N.
    IntActiP62623. 7 interactions.
    STRINGi511145.b0029.

    Structurei

    Secondary structure

    1
    316
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi2 – 54
    Helixi13 – 2917
    Beta strandi33 – 375
    Beta strandi39 – 413
    Helixi43 – 519
    Beta strandi54 – 596
    Helixi60 – 623
    Beta strandi68 – 714
    Helixi78 – 869
    Beta strandi90 – 934
    Helixi97 – 11216
    Beta strandi115 – 1206
    Helixi125 – 1317
    Beta strandi137 – 1393
    Beta strandi141 – 1444
    Helixi147 – 1526
    Beta strandi160 – 1656
    Beta strandi167 – 1693
    Helixi171 – 18414
    Beta strandi191 – 1933
    Helixi198 – 21316
    Beta strandi215 – 2206
    Helixi226 – 23712
    Beta strandi241 – 2477
    Helixi248 – 2503
    Helixi253 – 2553
    Turni256 – 2583
    Beta strandi260 – 2667
    Helixi272 – 28413
    Beta strandi289 – 2924
    Beta strandi300 – 3023
    Helixi306 – 3083

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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. Positions 1-310.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP62623.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni225 – 2273Substrate binding

    Sequence similaritiesi

    Belongs to the IspH family.Curated

    Phylogenomic databases

    eggNOGiCOG0761.
    HOGENOMiHOG000220192.
    KOiK03527.
    OMAiLEMYGAP.
    OrthoDBiEOG6HF624.
    PhylomeDBiP62623.

    Family and domain databases

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

    Sequencei

    Sequence statusi: Complete.

    P62623-1 [UniParc]FASTAAdd to Basket

    « Hide

    MQILLANPRG FCAGVDRAIS IVENALAIYG APIYVRHEVV HNRYVVDSLR    50
    ERGAIFIEQI SEVPDGAILI FSAHGVSQAV RNEAKSRDLT VFDATCPLVT 100
    KVHMEVARAS RRGEESILIG HAGHPEVEGT MGQYSNPEGG MYLVESPDDV 150
    WKLTVKNEEK LSFMTQTTLS VDDTSDVIDA LRKRFPKIVG PRKDDICYAT 200
    TNRQEAVRAL AEQAEVVLVV GSKNSSNSNR LAELAQRMGK RAFLIDDAKD 250
    IQEEWVKEVK CVGVTAGASA PDILVQNVVA RLQQLGGGEA IPLEGREENI 300
    VFEVPKELRV DIREVD 316
    Length:316
    Mass (Da):34,775
    Last modified:July 19, 2004 - v1
    Checksum:i0E7B378BD49AB771
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    YP_488335.1. NC_007779.1.

    Genome annotation databases

    EnsemblBacteriaiAAC73140; AAC73140; b0029.
    BAB96598; BAB96598; BAB96598.
    GeneIDi12933923.
    944777.
    KEGGiecj:Y75_p0029.
    eco:b0029.
    PATRICi32115149. VBIEscCol129921_0026.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    PIRi JE0403.
    RefSeqi NP_414570.1. NC_000913.3.
    YP_488335.1. NC_007779.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3F7T X-ray 1.80 A/B 1-316 [» ]
    3KE8 X-ray 1.70 A/B 1-316 [» ]
    3KE9 X-ray 1.90 A/B 1-316 [» ]
    3KEF X-ray 1.70 A/B 1-316 [» ]
    3KEL X-ray 1.80 A/B 1-316 [» ]
    3KEM X-ray 2.00 A/B 1-316 [» ]
    3SZL X-ray 1.60 A/B 1-316 [» ]
    3SZO X-ray 1.60 A/B 1-316 [» ]
    3SZU X-ray 1.40 A/B 1-316 [» ]
    3T0F X-ray 1.90 A/B 1-316 [» ]
    3T0G X-ray 2.10 A/B 1-316 [» ]
    3URK X-ray 1.50 A/B 1-316 [» ]
    3UTC X-ray 1.90 A/B 1-316 [» ]
    3UTD X-ray 1.70 A/B 1-316 [» ]
    3UV3 X-ray 1.60 A/B 1-316 [» ]
    3UV6 X-ray 1.70 A/B 1-316 [» ]
    3UV7 X-ray 1.60 A/B 1-316 [» ]
    3UWM X-ray 1.80 A/B 1-316 [» ]
    3ZGL X-ray 1.68 A/B 1-316 [» ]
    3ZGN X-ray 1.95 A/B 1-316 [» ]
    4EB3 X-ray 1.90 A/B 1-315 [» ]
    4H4C X-ray 1.80 A/B 1-315 [» ]
    4H4D X-ray 1.35 A/B 1-315 [» ]
    4H4E X-ray 1.70 A/B 1-315 [» ]
    ProteinModelPortali P62623.
    SMRi P62623. Positions 1-310.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-35808N.
    IntActi P62623. 7 interactions.
    STRINGi 511145.b0029.

    Proteomic databases

    PaxDbi P62623.
    PRIDEi P62623.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblBacteriai AAC73140 ; AAC73140 ; b0029 .
    BAB96598 ; BAB96598 ; BAB96598 .
    GeneIDi 12933923.
    944777.
    KEGGi ecj:Y75_p0029.
    eco:b0029.
    PATRICi 32115149. VBIEscCol129921_0026.

    Organism-specific databases

    EchoBASEi EB1073.
    EcoGenei EG11081. ispH.

    Phylogenomic databases

    eggNOGi COG0761.
    HOGENOMi HOG000220192.
    KOi K03527.
    OMAi LEMYGAP.
    OrthoDBi EOG6HF624.
    PhylomeDBi P62623.

    Enzyme and pathway databases

    UniPathwayi UPA00056 ; UER00097 .
    UPA00059 ; UER00105 .
    BioCyci EcoCyc:EG11081-MONOMER.
    ECOL316407:JW0027-MONOMER.
    MetaCyc:EG11081-MONOMER.
    BRENDAi 1.17.1.2. 2026.

    Miscellaneous databases

    EvolutionaryTracei P62623.
    PROi P62623.

    Gene expression databases

    Genevestigatori P62623.

    Family and domain databases

    HAMAPi MF_00191. IspH.
    InterProi IPR003451. LytB.
    [Graphical view ]
    Pfami PF02401. LYTB. 1 hit.
    [Graphical view ]
    TIGRFAMsi TIGR00216. ispH_lytB. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Studies on the nonmevalonate terpene biosynthetic pathway: metabolic role of IspH (LytB) protein."
      Rohdich F., Hecht S., Gaertner K., Adam P., Krieger C., Amslinger S., Arigoni D., Bacher A., Eisenreich W.
      Proc. Natl. Acad. Sci. U.S.A. 99:1158-1163(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION.
    2. "Nucleotide sequence of the lsp-dapB interval in Escherichia coli."
      Bouvier J., Stragier P.
      Nucleic Acids Res. 19:180-180(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    3. "Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region."
      Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A.
      Nucleic Acids Res. 20:3305-3308(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    5. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    6. "Identification of the Escherichia coli lytB gene, which is involved in penicillin tolerance and control of the stringent response."
      Gustafson C.E., Kaul S., Ishiguro E.E.
      J. Bacteriol. 175:1203-1205(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION.
    7. "LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli."
      Altincicek B., Kollas A.-K., Eberl M., Wiesner J., Sanderbrand S., Hintz M., Beck E., Jomaa H.
      FEBS Lett. 499:37-40(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PATHWAY.
      Strain: K12 / ATCC 23716 / DSM 498.
    8. "The lytB gene of Escherichia coli is essential and specifies a product needed for isoprenoid biosynthesis."
      McAteer S., Coulson A., McLennan N., Masters M.
      J. Bacteriol. 183:7403-7407(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PATHWAY.
    9. "Biosynthesis of terpenes: studies on 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase."
      Adam P., Hecht S., Eisenreich W., Kaiser J., Graewert T., Arigoni D., Bacher A., Rohdich F.
      Proc. Natl. Acad. Sci. U.S.A. 99:12108-12113(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY.
    10. "Isoprenoid biosynthesis via the methylerythritol phosphate pathway: the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB/IspH) from Escherichia coli is a [4Fe-4S] protein."
      Wolff M., Seemann M., Tse Sum Bui B., Frapart Y., Tritsch D., Garcia Estrabot A., Rodriguez-Concepcion M., Boronat A., Marquet A., Rohmer M.
      FEBS Lett. 541:115-120(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: IRON-SULFUR CLUSTER, SUBUNIT.
    11. "The deoxyxylulose phosphate pathway of isoprenoid biosynthesis: studies on the mechanisms of the reactions catalyzed by IspG and IspH protein."
      Rohdich F., Zepeck F., Adam P., Hecht S., Kaiser J., Laupitz R., Graewert T., Amslinger S., Eisenreich W., Bacher A., Arigoni D.
      Proc. Natl. Acad. Sci. U.S.A. 100:1586-1591(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY.
    12. Cited for: PRESENCE OF A 3FE-4S IRON-SULFUR CLUSTER, ENZYME REGULATION, KINETIC PARAMETERS, MUTAGENESIS OF CYS-12; CYS-96 AND CYS-197.
    13. "Structure of active IspH enzyme from Escherichia coli provides mechanistic insights into substrate reduction."
      Graewert T., Rohdich F., Span I., Bacher A., Eisenreich W., Eppinger J., Groll M.
      Angew. Chem. Int. Ed. Engl. 48:5756-5759(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR (3FE-4S), FUNCTION, COFACTOR, SUBUNIT, MUTAGENESIS OF HIS-41; HIS-74; VAL-99; HIS-124; GLU-126; THR-167; SER-225 AND ASN-227.
    14. "Probing the reaction mechanism of IspH protein by x-ray structure analysis."
      Graewert T., Span I., Eisenreich W., Rohdich F., Eppinger J., Bacher A., Groll M.
      Proc. Natl. Acad. Sci. U.S.A. 107:1077-1081(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND IRON-SULFUR (3FE-4S), FUNCTION, COFACTOR, SUBUNIT, MUTAGENESIS OF CYS-12; CYS-96 AND CYS-197.
    15. "Crystal structures of mutant IspH proteins reveal a rotation of the substrate's hydroxymethyl group during catalysis."
      Span I., Graewert T., Bacher A., Eisenreich W., Groll M.
      J. Mol. Biol. 416:1-9(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND IRON-SULFUR (4FE-4S), FUNCTION, COFACTOR, SUBUNIT, MUTAGENESIS OF GLU-126 AND THR-167.

    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: October 1, 2014
    This is version 91 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

    External Data

    Dasty 3