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Q8T6T2

- IMDH_CRYPV

UniProt

Q8T6T2 - IMDH_CRYPV

Protein

Inosine-5'-monophosphate dehydrogenase

Gene

56k.02

Organism
Cryptosporidium parvum
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 73 (01 Oct 2014)
      Sequence version 1 (01 Jun 2002)
      Previous versions | rss
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    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.1 PublicationUniRule annotation

    Catalytic activityi

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

    Cofactori

    Potassium.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.1 PublicationUniRule annotation

    Kineticsi

    1. KM=29 µM for Inosine 5'-phosphate1 Publication
    2. KM=150 µM for NAD+1 Publication

    Pathwayi

    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

    1. IMP dehydrogenase activity Source: UniProtKB-HAMAP
    2. metal ion binding Source: UniProtKB-HAMAP
    3. nucleotide binding Source: UniProtKB-HAMAP

    GO - Biological processi

    1. GMP biosynthetic process Source: UniProtKB-HAMAP

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    GMP biosynthesis, Purine biosynthesis

    Keywords - Ligandi

    Metal-binding, NAD, Potassium

    Enzyme and pathway databases

    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

    1. cytoplasm Source: UniProtKB-SubCell

    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.1 PublicationUniRule annotation

    Structurei

    Secondary structure

    1
    400
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 84
    Helixi12 – 143
    Beta strandi15 – 173
    Helixi26 – 283
    Beta strandi33 – 364
    Beta strandi39 – 479
    Turni51 – 533
    Helixi56 – 649
    Beta strandi68 – 714
    Beta strandi73 – 753
    Helixi77 – 8812
    Beta strandi133 – 1353
    Beta strandi138 – 1414
    Helixi146 – 1549
    Beta strandi158 – 1636
    Helixi170 – 18213
    Beta strandi186 – 1927
    Helixi195 – 2039
    Beta strandi207 – 2115
    Helixi221 – 2244
    Helixi231 – 24515
    Beta strandi249 – 2535
    Helixi258 – 2669
    Beta strandi270 – 2756
    Helixi276 – 2794
    Beta strandi288 – 2914
    Beta strandi294 – 3007
    Helixi305 – 3095
    Beta strandi332 – 3365
    Helixi341 – 35818
    Helixi364 – 3707
    Beta strandi373 – 3753
    Helixi378 – 3847
    Beta strandi388 – 3914

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3FFSX-ray3.19A/B/C/D1-400[»]
    4IXHX-ray2.10A/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

    MGTKNIGKGL TFEDILLVPN YSEVLPREVS LETKLTKNVS LKIPLISSAM    50
    DTVTEHLMAV GMARLGGIGI IHKNMDMESQ VNEVLKVKNW ISNLEKNEST 100
    PDQNLDKEST DGKDTKSNNN IDAYSNENLD NKGRLRVGAA IGVNEIERAK 150
    LLVEAGVDVI VLDSAHGHSL NIIRTLKEIK SKMNIDVIVG NVVTEEATKE 200
    LIENGADGIK VGIGPGSICT TRIVAGVGVP QITAIEKCSS VASKFGIPII 250
    ADGGIRYSGD IGKALAVGAS SVMIGSILAG TEESPGEKEL IGDTVYKYYR 300
    GMGSVGAMKS GSGDRYFQEK RPENKMVPEG IEGRVKYKGE MEGVVYQLVG 350
    GLRSCMGYLG SASIEELWKK SSYVEITTSG LRESHVHDVE IVKEVMNYSK 400
    Length:400
    Mass (Da):43,081
    Last modified:June 1, 2002 - v1
    Checksum:iDAAF96B44050DD18
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3FFS X-ray 3.19 A/B/C/D 1-400 [» ]
    4IXH X-ray 2.10 A/B/C/D 1-89 [» ]
    A/B/C/D 135-400 [» ]
    ProteinModelPortali Q8T6T2.
    SMRi Q8T6T2. Positions 7-377.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi Q8T6T2.
    ChEMBLi CHEMBL6145.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Enzyme and pathway databases

    UniPathwayi UPA00601 ; UER00295 .

    Miscellaneous databases

    EvolutionaryTracei Q8T6T2.

    Family and domain databases

    Gene3Di 3.20.20.70. 2 hits.
    HAMAPi MF_01964. IMPDH.
    InterProi IPR013785. Aldolase_TIM.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view ]
    Pfami PF00478. IMPDH. 1 hit.
    [Graphical view ]
    PROSITEi PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 73 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