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Protein

Inosine-5'-monophosphate dehydrogenase

Gene

56k.02

Organism
Cryptosporidium parvum
Status
Reviewed-Annotation score: Annotation score: 4 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.UniRule annotation1 Publication

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 (By similarity). Resistant to mycophenolic acid (MPA) inhibition.UniRule annotation1 Publication

Kineticsi

  1. KM=29 µM for Inosine 5'-phosphate1 Publication
  2. KM=150 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 (56k.02)
    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 sitei163 – 1631NADUniRule annotation
    Metal bindingi214 – 2141Potassium; via carbonyl oxygenUniRule annotation
    Metal bindingi216 – 2161Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei217 – 2171IMPUniRule annotation
    Active sitei219 – 2191Thioimidate intermediateUniRule annotation
    Metal bindingi219 – 2191Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei329 – 3291IMPUniRule annotation
    Metal bindingi383 – 3831Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi384 – 3841Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi385 – 3851Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi212 – 2143NADUniRule 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

    BRENDAi1.1.1.205. 1728.
    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
    ORF Names:56k.02, cgd6_20
    OrganismiCryptosporidium parvum
    Taxonomic identifieri5807 [NCBI]
    Taxonomic lineageiEukaryotaAlveolataApicomplexaConoidasidaCoccidiaEucoccidioridaEimeriorinaCryptosporidiidaeCryptosporidium

    Subcellular locationi

    • Cytoplasm UniRule annotation

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 400400Inosine-5'-monophosphate dehydrogenasePRO_0000415682Add
    BLAST

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation1 Publication

    Protein-protein interaction databases

    STRINGi353152.XP_625342.1.

    Structurei

    Secondary structure

    1
    400
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 84Combined sources
    Helixi12 – 143Combined sources
    Beta strandi15 – 173Combined sources
    Helixi26 – 283Combined sources
    Beta strandi33 – 364Combined sources
    Beta strandi39 – 479Combined sources
    Turni51 – 533Combined sources
    Helixi56 – 649Combined sources
    Beta strandi68 – 714Combined sources
    Beta strandi73 – 753Combined sources
    Helixi77 – 8812Combined sources
    Turni132 – 1343Combined sources
    Beta strandi138 – 1414Combined sources
    Helixi146 – 15510Combined sources
    Beta strandi158 – 1636Combined sources
    Beta strandi167 – 1693Combined sources
    Helixi170 – 18213Combined sources
    Beta strandi186 – 1927Combined sources
    Helixi195 – 2039Combined sources
    Beta strandi207 – 2115Combined sources
    Helixi221 – 2244Combined sources
    Helixi231 – 24212Combined sources
    Helixi243 – 2453Combined sources
    Beta strandi249 – 2535Combined sources
    Helixi258 – 2669Combined sources
    Beta strandi270 – 2745Combined sources
    Helixi276 – 2794Combined sources
    Beta strandi281 – 2844Combined sources
    Beta strandi288 – 2914Combined sources
    Beta strandi294 – 3007Combined sources
    Helixi305 – 3095Combined sources
    Beta strandi332 – 3365Combined sources
    Helixi341 – 35818Combined sources
    Helixi364 – 3707Combined sources
    Beta strandi373 – 3753Combined sources
    Helixi378 – 3847Combined sources
    Beta strandi388 – 3914Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3FFSX-ray3.19A/B/C/D1-400[»]
    4IXHX-ray2.10A/B/C/D1-89[»]
    A/B/C/D135-400[»]
    4QJ1X-ray2.42A/B/C/D1-400[»]
    4RV8X-ray2.05A/B/C/D1-89[»]
    A/B/C/D135-400[»]
    ProteinModelPortaliQ8T6T2.
    SMRiQ8T6T2. Positions 7-377.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8T6T2.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni252 – 2543IMP bindingUniRule annotation
    Regioni275 – 2762IMP bindingUniRule annotation
    Regioni299 – 3035IMP bindingUniRule annotation

    Sequence similaritiesi

    Belongs to the IMPDH/GMPR family.UniRule annotation

    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]
    PfamiPF00478. IMPDH. 1 hit.
    [Graphical view]
    PROSITEiPS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q8T6T2-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MGTKNIGKGL TFEDILLVPN YSEVLPREVS LETKLTKNVS LKIPLISSAM
    60 70 80 90 100
    DTVTEHLMAV GMARLGGIGI IHKNMDMESQ VNEVLKVKNW ISNLEKNEST
    110 120 130 140 150
    PDQNLDKEST DGKDTKSNNN IDAYSNENLD NKGRLRVGAA IGVNEIERAK
    160 170 180 190 200
    LLVEAGVDVI VLDSAHGHSL NIIRTLKEIK SKMNIDVIVG NVVTEEATKE
    210 220 230 240 250
    LIENGADGIK VGIGPGSICT TRIVAGVGVP QITAIEKCSS VASKFGIPII
    260 270 280 290 300
    ADGGIRYSGD IGKALAVGAS SVMIGSILAG TEESPGEKEL IGDTVYKYYR
    310 320 330 340 350
    GMGSVGAMKS GSGDRYFQEK RPENKMVPEG IEGRVKYKGE MEGVVYQLVG
    360 370 380 390 400
    GLRSCMGYLG SASIEELWKK SSYVEITTSG LRESHVHDVE IVKEVMNYSK
    Length:400
    Mass (Da):43,081
    Last modified:June 1, 2002 - v1
    Checksum:iDAAF96B44050DD18
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF426177 Genomic DNA. Translation: AAL83208.1.
    BX538350 Genomic DNA. Translation: CAD98604.1.
    FX115298 mRNA. Translation: BAJ77401.1.
    FX115945 mRNA. Translation: BAJ78048.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF426177 Genomic DNA. Translation: AAL83208.1.
    BX538350 Genomic DNA. Translation: CAD98604.1.
    FX115298 mRNA. Translation: BAJ77401.1.
    FX115945 mRNA. Translation: BAJ78048.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3FFSX-ray3.19A/B/C/D1-400[»]
    4IXHX-ray2.10A/B/C/D1-89[»]
    A/B/C/D135-400[»]
    4QJ1X-ray2.42A/B/C/D1-400[»]
    4RV8X-ray2.05A/B/C/D1-89[»]
    A/B/C/D135-400[»]
    ProteinModelPortaliQ8T6T2.
    SMRiQ8T6T2. Positions 7-377.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi353152.XP_625342.1.

    Chemistry

    BindingDBiQ8T6T2.
    ChEMBLiCHEMBL6145.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BRENDAi1.1.1.205. 1728.

    Miscellaneous databases

    EvolutionaryTraceiQ8T6T2.

    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]
    PfamiPF00478. IMPDH. 1 hit.
    [Graphical view]
    PROSITEiPS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: Iowa.
    2. "Integrated mapping, chromosomal sequencing and sequence analysis of Cryptosporidium parvum."
      Bankier A.T., Spriggs H.F., Fartmann B., Konfortov B.A., Madera M., Vogel C., Teichmann S.A., Ivens A., Dear P.H.
      Genome Res. 13:1787-1799(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Iowa.
    3. "Construction and analysis of full-length cDNA library of Cryptosporidium parvum."
      Yamagishi J., Wakaguri H., Sugano S., Kawano S., Fujisaki K., Sugimoto C., Watanabe J., Suzuki Y., Kimata I., Xuan X.
      Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: HNJ-1.
    4. "Cryptosporidium parvum IMP dehydrogenase: identification of functional, structural, and dynamic properties that can be exploited for drug design."
      Umejiego N.N., Li C., Riera T., Hedstrom L., Striepen B.
      J. Biol. Chem. 279:40320-40327(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-11, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ENZYME REGULATION.
    5. "The structural basis of Cryptosporidium-specific IMP dehydrogenase inhibitor selectivity."
      Macpherson I.S., Kirubakaran S., Gorla S.K., Riera T.V., D'Aquino J.A., Zhang M., Cuny G.D., Hedstrom L.
      J. Am. Chem. Soc. 132:1230-1231(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.19 ANGSTROMS).

    Entry informationi

    Entry nameiIMDH_CRYPV
    AccessioniPrimary (citable) accession number: Q8T6T2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 22, 2012
    Last sequence update: June 1, 2002
    Last modified: June 24, 2015
    This is version 79 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)

    Miscellaneousi

    Miscellaneous

    Cryptosporidium IMPDH was acquired through lateral transfer from eubacteria, and predictably the sensitivity to MPA differs from that of mammalian IMPDH forms. This divergence of parasite and host enzymes is exploited to design more potent parasite-specific inhibitors.

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    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.