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Protein

Inosine-5'-monophosphate dehydrogenase

Gene

guaB

Organism
Borrelia burgdorferi (strain ATCC 35210 / B31 / CIP 102532 / DSM 4680)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Essential for mouse infection by tick bite and critical for the survival in environments that appear to lack sufficient amounts of guanine, guanosine, and/or deoxyguanosine to support spirochete growth, such as mammalian host tissues.UniRule annotation2 Publications

Catalytic activityi

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH.UniRule annotation

Cofactori

K(+)UniRule annotation

Enzyme regulationi

Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.UniRule annotation

Kineticsi

  1. KM=29 µM for Inosine 5'-phosphate1 Publication
  2. KM=1100 µM for NAD+1 Publication

    Pathway:iXMP biosynthesis via de novo pathway

    This protein is involved in step 1 of the subpathway that synthesizes XMP from IMP.UniRule annotation
    Proteins known to be involved in this subpathway in this organism are:
    1. Inosine-5'-monophosphate dehydrogenase (guaB)
    This subpathway is part of the pathway XMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes XMP from IMP, the pathway XMP biosynthesis via de novo pathway and in Purine metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei172 – 1721NADUniRule annotation
    Metal bindingi224 – 2241Potassium; via carbonyl oxygenUniRule annotation
    Metal bindingi226 – 2261Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei227 – 2271IMPUniRule annotation
    Active sitei229 – 2291Thioimidate intermediateUniRule annotation
    Metal bindingi229 – 2291Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei340 – 3401IMPUniRule annotation
    Metal bindingi394 – 3941Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi395 – 3951Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi396 – 3961Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi222 – 2243NADUniRule annotation

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    GMP biosynthesis, Purine biosynthesis

    Keywords - Ligandi

    Metal-binding, NAD, Potassium

    Enzyme and pathway databases

    BioCyciBBUR224326:G9SO-1498-MONOMER.
    BRENDAi1.1.1.205. 902.
    UniPathwayiUPA00601; UER00295.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inosine-5'-monophosphate dehydrogenaseUniRule annotation (EC:1.1.1.205UniRule annotation)
    Short name:
    IMP dehydrogenaseUniRule annotation
    Short name:
    IMPDUniRule annotation
    Short name:
    IMPDHUniRule annotation
    Gene namesi
    Name:guaBUniRule annotation
    Ordered Locus Names:BB_B17
    Encoded oniPlasmid cp26 (circular 26 kb)0 Publication
    OrganismiBorrelia burgdorferi (strain ATCC 35210 / B31 / CIP 102532 / DSM 4680)
    Taxonomic identifieri224326 [NCBI]
    Taxonomic lineageiBacteriaSpirochaetesSpirochaetalesBorreliaceaeBorreliaBorrelia burgdorferi group
    ProteomesiUP000001807 Componenti: Plasmid cp26

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 404403Inosine-5'-monophosphate dehydrogenasePRO_0000093692Add
    BLAST

    Proteomic databases

    PRIDEiP49058.

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation1 Publication

    Structurei

    Secondary structure

    1
    404
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi12 – 143Combined sources
    Beta strandi15 – 173Combined sources
    Helixi26 – 283Combined sources
    Beta strandi33 – 386Combined sources
    Beta strandi40 – 478Combined sources
    Turni51 – 533Combined sources
    Helixi56 – 6510Combined sources
    Beta strandi67 – 715Combined sources
    Beta strandi73 – 753Combined sources
    Helixi77 – 8812Combined sources
    Beta strandi145 – 1484Combined sources
    Helixi154 – 16310Combined sources
    Beta strandi167 – 1715Combined sources
    Helixi179 – 19113Combined sources
    Beta strandi196 – 2027Combined sources
    Helixi205 – 2128Combined sources
    Turni213 – 2153Combined sources
    Beta strandi217 – 2215Combined sources
    Helixi230 – 2356Combined sources
    Helixi241 – 25212Combined sources
    Beta strandi258 – 2636Combined sources
    Helixi268 – 27710Combined sources
    Beta strandi280 – 2845Combined sources
    Helixi286 – 2894Combined sources
    Beta strandi294 – 2963Combined sources
    Beta strandi298 – 3014Combined sources
    Beta strandi304 – 3074Combined sources
    Helixi352 – 37019Combined sources
    Helixi375 – 3806Combined sources
    Beta strandi384 – 3863Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1EEPX-ray2.40A/B1-404[»]
    ProteinModelPortaliP49058.
    SMRiP49058. Positions 3-389.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP49058.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni262 – 2643IMP bindingUniRule annotation
    Regioni285 – 2862IMP bindingUniRule annotation
    Regioni309 – 3135IMP bindingUniRule annotation

    Sequence similaritiesi

    Belongs to the IMPDH/GMPR family.UniRule annotation

    Phylogenomic databases

    eggNOGiCOG0517.
    KOiK00088.
    OMAiPEHEPYS.
    OrthoDBiEOG6GTZPV.

    Family and domain databases

    Gene3Di3.20.20.70. 2 hits.
    HAMAPiMF_01964. IMPDH.
    InterProiIPR013785. Aldolase_TIM.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 1 hit.
    PfamiPF00478. IMPDH. 1 hit.
    [Graphical view]
    PROSITEiPS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P49058-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPNKITKEAL TFDDVSLIPR KSSVLPSEVS LKTQLTKNIS LNIPFLSSAM
    60 70 80 90 100
    DTVTESQMAI AIAKEGGIGI IHKNMSIEAQ RKEIEKVKTY KFQKTINTNG
    110 120 130 140 150
    DTNEQKPEIF TAKQHLEKSD AYKNAEHKED FPNACKDLNN KLRVGAAVSI
    160 170 180 190 200
    DIDTIERVEE LVKAHVDILV IDSAHGHSTR IIELIKKIKT KYPNLDLIAG
    210 220 230 240 250
    NIVTKEAALD LISVGADCLK VGIGPGSICT TRIVAGVGVP QITAICDVYE
    260 270 280 290 300
    ACNNTNICII ADGGIRFSGD VVKAIAAGAD SVMIGNLFAG TKESPSEEII
    310 320 330 340 350
    YNGKKFKSYV GMGSISAMKR GSKSRYFQLE NNEPKKLVPE GIEGMVPYSG
    360 370 380 390 400
    KLKDILTQLK GGLMSGMGYL GAATISDLKI NSKFVKISHS SLKESHPHDV

    FSIT
    Length:404
    Mass (Da):43,768
    Last modified:February 1, 1996 - v1
    Checksum:iA91D6D6C5CE522F1
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U13372 Genomic DNA. Translation: AAA53247.1.
    AE000792 Genomic DNA. Translation: AAC66314.1.
    PIRiE70218.
    RefSeqiNP_047003.1. NC_001903.1.
    WP_010890582.1. NC_001903.1.

    Genome annotation databases

    EnsemblBacteriaiAAC66314; AAC66314; BB_B17.
    GeneIDi1194400.
    KEGGibbu:BB_B17.
    PATRICi20559101. VBIBorBur75917_1605.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U13372 Genomic DNA. Translation: AAA53247.1.
    AE000792 Genomic DNA. Translation: AAC66314.1.
    PIRiE70218.
    RefSeqiNP_047003.1. NC_001903.1.
    WP_010890582.1. NC_001903.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1EEPX-ray2.40A/B1-404[»]
    ProteinModelPortaliP49058.
    SMRiP49058. Positions 3-389.
    ModBaseiSearch...
    MobiDBiSearch...

    Chemistry

    BindingDBiP49058.

    Proteomic databases

    PRIDEiP49058.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC66314; AAC66314; BB_B17.
    GeneIDi1194400.
    KEGGibbu:BB_B17.
    PATRICi20559101. VBIBorBur75917_1605.

    Phylogenomic databases

    eggNOGiCOG0517.
    KOiK00088.
    OMAiPEHEPYS.
    OrthoDBiEOG6GTZPV.

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BioCyciBBUR224326:G9SO-1498-MONOMER.
    BRENDAi1.1.1.205. 902.

    Miscellaneous databases

    EvolutionaryTraceiP49058.

    Family and domain databases

    Gene3Di3.20.20.70. 2 hits.
    HAMAPiMF_01964. IMPDH.
    InterProiIPR013785. Aldolase_TIM.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 1 hit.
    PfamiPF00478. IMPDH. 1 hit.
    [Graphical view]
    PROSITEiPS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Plasmid location of Borrelia purine biosynthesis gene homologs."
      Margolis N., Hogan D., Tilly K., Rosa P.
      J. Bacteriol. 176:6427-6432(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: ATCC 35210 / B31 / CIP 102532 / DSM 4680.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 35210 / B31 / CIP 102532 / DSM 4680.
    3. "Expression, purification, and characterization of inosine 5'-monophosphate dehydrogenase from Borrelia burgdorferi."
      Zhou X., Cahoon M., Rosa P., Hedstrom L.
      J. Biol. Chem. 272:21977-21981(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-7, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
      Strain: ATCC 35210 / B31 / CIP 102532 / DSM 4680.
    4. "GuaA and GuaB are essential for Borrelia burgdorferi survival in the tick-mouse infection cycle."
      Jewett M.W., Lawrence K.A., Bestor A., Byram R., Gherardini F., Rosa P.A.
      J. Bacteriol. 191:6231-6241(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
      Strain: ATCC 35210 / B31 / CIP 102532 / DSM 4680.
    5. "Crystal structure at 2.4-A resolution of Borrelia burgdorferi inosine 5'-monophosphate dehydrogenase: evidence of a substrate-induced hinged-lid motion by loop 6."
      McMillan F.M., Cahoon M., White A., Hedstrom L., Petsko G.A., Ringe D.
      Biochemistry 39:4533-4542(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).

    Entry informationi

    Entry nameiIMDH_BORBU
    AccessioniPrimary (citable) accession number: P49058
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: July 22, 2015
    This is version 116 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, Plasmid, Reference proteome

    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.