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Protein

Inosine-5'-monophosphate dehydrogenase

Gene

56k.02

Organism
Cryptosporidium parvum
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.1 Publication

Catalytic activityi

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH.1 Publication

Cofactori

K+By similarity

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. Resistant to mycophenolic acid (MPA) inhibition (PubMed:15269207).By similarity1 Publication

Kineticsi

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

    Pathwayi: XMP biosynthesis via de novo pathway

    This protein is involved in step 1 of the subpathway that synthesizes XMP from IMP.1 Publication
    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)DescriptionActionsGraphical viewLength
    Binding sitei163NADBy similarity1
    Metal bindingi214Potassium; via carbonyl oxygenBy similarity1
    Metal bindingi216Potassium; via carbonyl oxygenBy similarity1
    Binding sitei217IMP1 Publication1
    Active sitei219Thioimidate intermediateBy similarity1
    Metal bindingi219Potassium; via carbonyl oxygenBy similarity1
    Active sitei315Proton acceptorBy similarity1
    Binding sitei329IMP1 Publication1
    Metal bindingi383Potassium; via carbonyl oxygen; shared with tetrameric partnerBy similarity1
    Metal bindingi384Potassium; via carbonyl oxygen; shared with tetrameric partnerBy similarity1
    Metal bindingi385Potassium; via carbonyl oxygen; shared with tetrameric partnerBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi212 – 214NADBy similarity3

    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 dehydrogenase1 Publication (EC:1.1.1.2051 Publication)
    Short name:
    IMP dehydrogenase1 Publication
    Short name:
    IMPD
    Short name:
    IMPDH1 Publication
    Gene namesi
    ORF Names:56k.02, cgd6_20
    OrganismiCryptosporidium parvum
    Taxonomic identifieri5807 [NCBI]
    Taxonomic lineageiEukaryotaAlveolataApicomplexaConoidasidaCoccidiaEucoccidioridaEimeriorinaCryptosporidiidaeCryptosporidium

    Subcellular locationi

    • Cytoplasm By similarity

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Chemistry databases

    ChEMBLiCHEMBL6145.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004156821 – 400Inosine-5'-monophosphate dehydrogenaseAdd BLAST400

    Interactioni

    Subunit structurei

    Homotetramer.1 Publication

    Protein-protein interaction databases

    STRINGi353152.XP_625342.1.

    Chemistry databases

    BindingDBiQ8T6T2.

    Structurei

    Secondary structure

    1400
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi5 – 8Combined sources4
    Helixi12 – 14Combined sources3
    Beta strandi15 – 17Combined sources3
    Helixi26 – 28Combined sources3
    Beta strandi33 – 36Combined sources4
    Beta strandi39 – 47Combined sources9
    Turni51 – 53Combined sources3
    Helixi56 – 64Combined sources9
    Beta strandi68 – 71Combined sources4
    Beta strandi73 – 75Combined sources3
    Helixi77 – 88Combined sources12
    Turni132 – 134Combined sources3
    Beta strandi138 – 141Combined sources4
    Helixi146 – 155Combined sources10
    Beta strandi158 – 163Combined sources6
    Beta strandi167 – 169Combined sources3
    Helixi170 – 182Combined sources13
    Beta strandi186 – 192Combined sources7
    Helixi195 – 203Combined sources9
    Beta strandi207 – 211Combined sources5
    Helixi221 – 224Combined sources4
    Helixi231 – 242Combined sources12
    Helixi243 – 245Combined sources3
    Beta strandi249 – 253Combined sources5
    Helixi258 – 266Combined sources9
    Beta strandi270 – 274Combined sources5
    Helixi276 – 279Combined sources4
    Beta strandi281 – 284Combined sources4
    Beta strandi288 – 291Combined sources4
    Beta strandi294 – 300Combined sources7
    Helixi305 – 309Combined sources5
    Beta strandi332 – 336Combined sources5
    Helixi341 – 358Combined sources18
    Helixi364 – 370Combined sources7
    Beta strandi373 – 375Combined sources3
    Helixi378 – 384Combined sources7
    Beta strandi388 – 391Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8T6T2.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni252 – 254IMP binding1 Publication3
    Regioni275 – 276IMP binding1 Publication2
    Regioni299 – 303IMP binding1 Publication5

    Sequence similaritiesi

    Belongs to the IMPDH/GMPR family.Curated

    Phylogenomic databases

    eggNOGiKOG2550. Eukaryota.
    COG0516. LUCA.

    Family and domain databases

    CDDicd00381. IMPDH. 1 hit.
    Gene3Di3.20.20.70. 2 hits.
    InterProiIPR013785. Aldolase_TIM.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 2 hits.
    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

    Mass spectrometryi

    Molecular mass is 42904 Da from positions 2 - 400. Determined by MALDI. 1 Publication

    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.

    Genome annotation databases

    EnsemblProtistsiCAD98604; CAD98604; 56k.02.

    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
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi353152.XP_625342.1.

    Chemistry databases

    BindingDBiQ8T6T2.
    ChEMBLiCHEMBL6145.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblProtistsiCAD98604; CAD98604; 56k.02.

    Phylogenomic databases

    eggNOGiKOG2550. Eukaryota.
    COG0516. LUCA.

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BRENDAi1.1.1.205. 1728.

    Miscellaneous databases

    EvolutionaryTraceiQ8T6T2.

    Family and domain databases

    CDDicd00381. IMPDH. 1 hit.
    Gene3Di3.20.20.70. 2 hits.
    InterProiIPR013785. Aldolase_TIM.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 2 hits.
    PfamiPF00478. IMPDH. 1 hit.
    [Graphical view]
    PROSITEiPS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    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: November 2, 2016
    This is version 86 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.1 Publication

    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

    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.