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Protein

Inosine-5'-monophosphate dehydrogenase

Gene
N/A
Organism
Leishmania donovani
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.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. Potently inhibited by MPA. Inhibited by XMP and GMP.UniRule annotation1 Publication

Kineticsi

  1. KM=33 µM for Inosine 5'-phosphate1 Publication
  2. KM=390 µM for NAD+1 Publication

    Pathway: XMP 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
    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
    Metal bindingi322 – 3221Potassium; via carbonyl oxygenUniRule annotation
    Metal bindingi324 – 3241Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei325 – 3251IMPUniRule annotation
    Active sitei327 – 3271Thioimidate intermediateUniRule annotation
    Metal bindingi327 – 3271Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei437 – 4371IMPUniRule annotation
    Metal bindingi496 – 4961Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi497 – 4971Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi498 – 4981Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi270 – 2723NADUniRule annotation
    Nucleotide bindingi320 – 3223NADUniRule 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. 2947.
    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
    OrganismiLeishmania donovani
    Taxonomic identifieri5661 [NCBI]
    Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeLeishmaniinaeLeishmania

    Subcellular locationi

    • Glycosome UniRule annotation1 Publication

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Glycosome, Peroxisome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 514514Inosine-5'-monophosphate dehydrogenasePRO_0000093675Add
    BLAST

    Interactioni

    Subunit structurei

    Heterotetramer. Interacts with glycosomal protein sorting receptor PEX5.1 Publication

    Protein-protein interaction databases

    STRINGi5661.XP_003860332.1.

    Structurei

    3D structure databases

    ProteinModelPortaliP21620.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini112 – 17160CBS 1UniRule annotationAdd
    BLAST
    Domaini175 – 23359CBS 2UniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni360 – 3623IMP bindingUniRule annotation
    Regioni383 – 3842IMP bindingUniRule annotation
    Regioni407 – 4115IMP bindingUniRule annotation

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi512 – 5143Microbody targeting signalUniRule annotation

    Sequence similaritiesi

    Belongs to the IMPDH/GMPR family.UniRule annotation
    Contains 2 CBS domains.UniRule annotation

    Keywords - Domaini

    CBS domain, Repeat

    Phylogenomic databases

    KOiK00088.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    HAMAPiMF_01964. IMPDH.
    InterProiIPR013785. Aldolase_TIM.
    IPR000644. CBS_dom.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 1 hit.
    PfamiPF00571. CBS. 2 hits.
    PF00478. IMPDH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000130. IMPDH. 1 hit.
    SMARTiSM00116. CBS. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P21620-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MATNNANYRI KTIKDGCTAE ELFRGDGLTY NDFIILPGFI DFGAADVNIS
    60 70 80 90 100
    GQFTKRIRLH IPIVSSPMDT ITENEMAKTM ALMGGVGVLH NNCTVERQVE
    110 120 130 140 150
    MVKSVKAYRN GFISKPKSVP PNTPISNIIR IKEEKGISGI LVTENGDPHG
    160 170 180 190 200
    KLLGIVCTKD IDYVKNKDTP VSAVMTRREK MTVERAPIQL EEAMDVLNRS
    210 220 230 240 250
    RYGYLPIVNE NDEVVNLCSR RDAVRARDYP HSTLDKSGRL ICAAATSTRP
    260 270 280 290 300
    EDKRRVAALA DVGVDVLVLD SSQGNTIYQI AFIKWVKSTY PHLEVVAGNV
    310 320 330 340 350
    VTQDQAKNLI DAGADGIRIG MGSGSICITQ EVLACGRPQG TAVYKVAQYC
    360 370 380 390 400
    ASRGVPCTAD GGLRQVGDIC KALAIGANCA MLGGMLSGTT ETPGEYFFKG
    410 420 430 440 450
    GVRLKVYRGM GSLEAMSQGK ESGKRYLSEN EAVQVAQGVS GNVVDKGSAA
    460 470 480 490 500
    KLIAYVSKGL QQSAQDIGEI SFDAIREKMY AGQVLFSRRS PTAQGEGGVH
    510
    SLHSYEKKLF AAKM
    Length:514
    Mass (Da):55,552
    Last modified:May 1, 1991 - v1
    Checksum:iE251FCC1362D60E5
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M55667 Genomic DNA. Translation: AAA29253.1.
    PIRiA38668.
    RefSeqiXP_003860332.1. XM_003860284.1.

    Genome annotation databases

    GeneIDi13386143.
    KEGGildo:LDBPK_191590.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M55667 Genomic DNA. Translation: AAA29253.1.
    PIRiA38668.
    RefSeqiXP_003860332.1. XM_003860284.1.

    3D structure databases

    ProteinModelPortaliP21620.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi5661.XP_003860332.1.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi13386143.
    KEGGildo:LDBPK_191590.

    Phylogenomic databases

    KOiK00088.

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BRENDAi1.1.1.205. 2947.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    HAMAPiMF_01964. IMPDH.
    InterProiIPR013785. Aldolase_TIM.
    IPR000644. CBS_dom.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 1 hit.
    PfamiPF00571. CBS. 2 hits.
    PF00478. IMPDH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000130. IMPDH. 1 hit.
    SMARTiSM00116. CBS. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    1. "Amplification and molecular cloning of the IMP dehydrogenase gene of Leishmania donovani."
      Wilson K.E., Collart F.R., Huberman E., Stringer J.R., Ullman B.
      J. Biol. Chem. 266:1665-1671(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Kinetic characterization of inosine monophosphate dehydrogenase of Leishmania donovani."
      Dobie F., Berg A., Boitz J.M., Jardim A.
      Mol. Biochem. Parasitol. 152:11-21(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH PEX5, SUBUNIT.

    Entry informationi

    Entry nameiIMDH_LEIDO
    AccessioniPrimary (citable) accession number: P21620
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 1991
    Last sequence update: May 1, 1991
    Last modified: June 24, 2015
    This is version 102 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)

    Miscellaneousi

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. 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.