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Protein

Inosine-5'-monophosphate dehydrogenase

Gene
N/A
Organism
Toxoplasma gondii
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. Potently inhibited by MPA and adenine dinucleotide analogs such as thiazole-4-carboxamide adenine dinucleotide (TAD).UniRule annotation1 Publication

Kineticsi

  1. KM=144 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.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)DescriptionActionsGraphical viewLength
    Metal bindingi310Potassium; via carbonyl oxygenUniRule annotation1
    Metal bindingi312Potassium; via carbonyl oxygenUniRule annotation1
    Binding sitei313IMPUniRule annotation1
    Active sitei315Thioimidate intermediateUniRule annotation1
    Metal bindingi315Potassium; via carbonyl oxygenUniRule annotation1
    Active sitei465Proton acceptorUniRule annotation1
    Binding sitei477IMPUniRule annotation1
    Metal bindingi536Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1
    Metal bindingi537Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi258 – 260NADUniRule annotation3
    Nucleotide bindingi308 – 310NADUniRule annotation3

    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. 6411.
    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
    OrganismiToxoplasma gondii
    Taxonomic identifieri5811 [NCBI]
    Taxonomic lineageiEukaryotaAlveolataApicomplexaConoidasidaCoccidiaEucoccidioridaEimeriorinaSarcocystidaeToxoplasma

    Subcellular locationi

    • Cytoplasm UniRule annotation1 Publication

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004156831 – 551Inosine-5'-monophosphate dehydrogenaseAdd BLAST551

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation

    Protein-protein interaction databases

    STRINGi5811.TGME49_033110.

    Structurei

    3D structure databases

    ProteinModelPortaliQ4VRV8.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini102 – 163CBS 1UniRule annotationAdd BLAST62
    Domaini165 – 221CBS 2UniRule annotationAdd BLAST57

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni349 – 351IMP bindingUniRule annotation3
    Regioni372 – 373IMP bindingUniRule annotation2
    Regioni396 – 400IMP bindingUniRule annotation5

    Sequence similaritiesi

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

    Keywords - Domaini

    CBS domain, Repeat

    Phylogenomic databases

    eggNOGiKOG2550. Eukaryota.
    COG0516. LUCA.
    COG0517. LUCA.

    Family and domain databases

    CDDicd00381. IMPDH. 1 hit.
    Gene3Di3.20.20.70. 2 hits.
    HAMAPiMF_01964. IMPDH. 1 hit.
    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. 3 hits.
    PfamiPF00571. CBS. 2 hits.
    PF00478. IMPDH. 2 hits.
    [Graphical view]
    SMARTiSM00116. CBS. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform TgIMPDH (identifier: Q4VRV8-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MADGWDAEKI FNTTVFGFTY DDLILMPGHI DFGVNDVDLS TRITRNLHVR
    60 70 80 90 100
    TPIVSSPMDT VTEHRMAIGC ALMGGMGVIH NNMETARQVA EVQKVKRYEN
    110 120 130 140 150
    GFILDPFVLR PSDSVADVYR IKEKYGYSSV PITDTGMLGG KLLGIVTSRD
    160 170 180 190 200
    IDFLTDVHTP LSEVMTSDLV VGHEPVQLAE ANELLRESKK GKLPIVNDNF
    210 220 230 240 250
    ELVALISRND LKKNREFPLA SKDSNKQLLV GAAVSTKPHD IERAKALQEA
    260 270 280 290 300
    GADVLVVDSS QGDSIYQVDL VKRLKAAFPE LQIIGGNVVT ARQAKSLIDA
    310 320 330 340 350
    GVDGLRIGMG SGSICTTQVV CAVGRAQATA VYHVCKYARE HGDVPCIADG
    360 370 380 390 400
    GIQNSGHVMK ALALGANAVM MGSMLAGTEE APGEYYFHNG VRVKTYRGMG
    410 420 430 440 450
    SLDAMRAGTR RTASPPARGL RSPEASPSTA ASSGGASRAS ALSEASPSAK
    460 470 480 490 500
    SEASRTSTST GSAARYFAEN QTIRVAQGVS GCVVDKGTVM QLIPYVIQGV
    510 520 530 540 550
    KHGMQDIGAR TLRDLHAQLV GGELRFDVRS GAAQREGDVH DLHSFERKLY

    A
    Length:551
    Mass (Da):59,047
    Last modified:July 5, 2005 - v1
    Checksum:i788A1DAC369E3DE9
    GO
    Isoform TgIMPDH-S (identifier: Q4VRV8-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         361-551: ALALGANAVM...LHSFERKLYA → VWRCAEGRRCS

    Note: Lacks the active-site flap.
    Show »
    Length:371
    Mass (Da):40,366
    Checksum:i8376164171422C8F
    GO

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_042319361 – 551ALALG…RKLYA → VWRCAEGRRCS in isoform TgIMPDH-S. 1 PublicationAdd BLAST191

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY663109 mRNA. Translation: AAV73841.1.
    AY661469 mRNA. Translation: AAV74388.1.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY663109 mRNA. Translation: AAV73841.1.
    AY661469 mRNA. Translation: AAV74388.1.

    3D structure databases

    ProteinModelPortaliQ4VRV8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi5811.TGME49_033110.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Phylogenomic databases

    eggNOGiKOG2550. Eukaryota.
    COG0516. LUCA.
    COG0517. LUCA.

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BRENDAi1.1.1.205. 6411.

    Family and domain databases

    CDDicd00381. IMPDH. 1 hit.
    Gene3Di3.20.20.70. 2 hits.
    HAMAPiMF_01964. IMPDH. 1 hit.
    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. 3 hits.
    PfamiPF00571. CBS. 2 hits.
    PF00478. IMPDH. 2 hits.
    [Graphical view]
    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...

    Entry informationi

    Entry nameiIMDH_TOXGO
    AccessioniPrimary (citable) accession number: Q4VRV8
    Secondary accession number(s): Q4VRV6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 22, 2012
    Last sequence update: July 5, 2005
    Last modified: October 5, 2016
    This is version 69 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

    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.