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Protein

Inosine-5'-monophosphate dehydrogenase

Gene

IMPDH

Organism
Tritrichomonas foetus (Trichomonas foetus) (Tritrichomonas suis)
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. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism.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.UniRule annotation1 Publication

Kineticsi

  1. KM=1.7 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.UniRule annotation
    Proteins known to be involved in this subpathway in this organism are:
    1. Inosine-5'-monophosphate dehydrogenase (IMPDH)
    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 bindingi20Potassium 2; via carbonyl oxygen1 Publication1
    Metal bindingi22Potassium 21 Publication1
    Metal bindingi264Potassium 2; shared with tetrameric partner1 Publication1
    Metal bindingi266Potassium 2; via carbonyl oxygen; shared with tetrameric partner1 Publication1
    Metal bindingi314Potassium 1; via carbonyl oxygen1 Publication1
    Metal bindingi316Potassium 1; via carbonyl oxygen1 Publication1
    Binding sitei317IMP1
    Active sitei319Thioimidate intermediateUniRule annotation2 Publications1
    Metal bindingi319Potassium 1; via carbonyl oxygen1 Publication1
    Active sitei418Proton acceptorUniRule annotation1
    Binding sitei431IMP1
    Metal bindingi460Potassium 2; via carbonyl oxygen1 Publication1
    Metal bindingi485Potassium 1; via carbonyl oxygen; shared with tetrameric partner1 Publication1
    Metal bindingi486Potassium 1; via carbonyl oxygen; shared with tetrameric partner1 Publication1
    Metal bindingi487Potassium 1; via carbonyl oxygen; shared with tetrameric partner1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi261 – 263NAD3
    Nucleotide bindingi312 – 314NAD3

    GO - Molecular functioni

    • IMP dehydrogenase activity Source: UniProtKB-HAMAP
    • metal ion binding Source: UniProtKB-HAMAP
    • nucleotide binding Source: UniProtKB

    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

    SABIO-RKP50097.
    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
    Name:IMPDHUniRule annotation
    OrganismiTritrichomonas foetus (Trichomonas foetus) (Tritrichomonas suis)
    Taxonomic identifieri56690 [NCBI]
    Taxonomic lineageiEukaryotaParabasaliaTritrichomonadidaTritrichomonadidaeTritrichomonas

    Subcellular locationi

    • Cytoplasm UniRule annotation

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi319C → S: Has less than 0.06% of the wild-type activity. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000936761 – 503Inosine-5'-monophosphate dehydrogenaseAdd BLAST503

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation4 Publications

    Structurei

    Secondary structure

    1503
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi12 – 14Combined sources3
    Beta strandi15 – 17Combined sources3
    Helixi28 – 30Combined sources3
    Beta strandi49 – 56Combined sources8
    Turni60 – 62Combined sources3
    Helixi65 – 73Combined sources9
    Beta strandi77 – 80Combined sources4
    Beta strandi82 – 84Combined sources3
    Helixi86 – 97Combined sources12
    Turni98 – 100Combined sources3
    Beta strandi235 – 238Combined sources4
    Beta strandi240 – 242Combined sources3
    Helixi243 – 253Combined sources11
    Beta strandi256 – 260Combined sources5
    Helixi268 – 281Combined sources14
    Helixi282 – 284Combined sources3
    Beta strandi287 – 292Combined sources6
    Helixi295 – 304Combined sources10
    Beta strandi307 – 311Combined sources5
    Helixi317 – 321Combined sources5
    Turni322 – 325Combined sources4
    Helixi331 – 349Combined sources19
    Beta strandi350 – 352Combined sources3
    Beta strandi355 – 359Combined sources5
    Helixi364 – 372Combined sources9
    Beta strandi376 – 381Combined sources6
    Helixi382 – 385Combined sources4
    Beta strandi390 – 392Combined sources3
    Beta strandi394 – 397Combined sources4
    Beta strandi400 – 406Combined sources7
    Helixi411 – 414Combined sources4
    Helixi416 – 419Combined sources4
    Beta strandi421 – 423Combined sources3
    Beta strandi434 – 438Combined sources5
    Helixi443 – 460Combined sources18
    Helixi466 – 472Combined sources7
    Beta strandi475 – 477Combined sources3
    Turni480 – 482Combined sources3
    Turni484 – 486Combined sources3
    Beta strandi490 – 493Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1AK5X-ray2.30A1-503[»]
    1LRTX-ray2.20A/B/C/D2-503[»]
    1ME7X-ray2.15A1-503[»]
    1ME8X-ray1.90A1-503[»]
    1ME9X-ray2.20A1-503[»]
    1MEHX-ray1.95A1-503[»]
    1MEIX-ray2.20A1-503[»]
    1MEWX-ray2.15A1-503[»]
    1PVNX-ray2.00A/B/C/D2-503[»]
    DisProtiDP00399.
    ProteinModelPortaliP50097.
    SMRiP50097.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP50097.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini103 – 163CBS 1UniRule annotationAdd BLAST61
    Domaini167 – 228CBS 2UniRule annotationAdd BLAST62

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni358 – 360IMP binding3
    Regioni381 – 382IMP binding2
    Regioni405 – 409IMP binding5

    Sequence similaritiesi

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

    Keywords - Domaini

    CBS domain, Repeat

    Family and domain databases

    CDDicd00381. IMPDH. 1 hit.
    Gene3Di3.20.20.70. 1 hit.
    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]
    PfamiPF00571. CBS. 1 hit.
    PF00478. IMPDH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000130. IMPDH. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P50097-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAKYYNEPCH TFNEYLLIPG LSTVDCIPSN VNLSTPLVKF QKGQQSEINL
    60 70 80 90 100
    KIPLVSAIMQ SVSGEKMAIA LAREGGISFI FGSQSIESQA AMVHAVKNFK
    110 120 130 140 150
    AGFVVSDSNV KPDQTFADVL AISQRTTHNT VAVTDDGTPH GVLLGLVTQR
    160 170 180 190 200
    DYPIDLTQTE TKVSDMMTPF SKLVTAHQDT KLSEANKIIW EKKLNALPII
    210 220 230 240 250
    DDDQHLRYIV FRKDYDRSQV CHNELVDSQK RYLVGAGINT RDFRERVPAL
    260 270 280 290 300
    VEAGADVLCI DSSDGFSEWQ KITIGWIREK YGDKVKVGAG NIVDGEGFRY
    310 320 330 340 350
    LADAGADFIK IGIGGGSICI TREQKGIGRG QATAVIDVVA ERNKYFEETG
    360 370 380 390 400
    IYIPVCSDGG IVYDYHMTLA LAMGADFIML GRYFARFEES PTRKVTINGS
    410 420 430 440 450
    VMKEYWGEGS SRARNWQRYD LGGKQKLSFE EGVDSYVPYA GKLKDNVEAS
    460 470 480 490 500
    LNKVKSTMCN CGALTIPQLQ SKAKITLVSS VSIVEGGAHD VIVKDRINDY

    HPK
    Length:503
    Mass (Da):55,473
    Last modified:October 1, 1996 - v1
    Checksum:iE204EADE7ECC4134
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L18917 Genomic DNA. Translation: AAB01581.1.
    PIRiA58910.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L18917 Genomic DNA. Translation: AAB01581.1.
    PIRiA58910.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1AK5X-ray2.30A1-503[»]
    1LRTX-ray2.20A/B/C/D2-503[»]
    1ME7X-ray2.15A1-503[»]
    1ME8X-ray1.90A1-503[»]
    1ME9X-ray2.20A1-503[»]
    1MEHX-ray1.95A1-503[»]
    1MEIX-ray2.20A1-503[»]
    1MEWX-ray2.15A1-503[»]
    1PVNX-ray2.00A/B/C/D2-503[»]
    DisProtiDP00399.
    ProteinModelPortaliP50097.
    SMRiP50097.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    SABIO-RKP50097.

    Miscellaneous databases

    EvolutionaryTraceiP50097.

    Family and domain databases

    CDDicd00381. IMPDH. 1 hit.
    Gene3Di3.20.20.70. 1 hit.
    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]
    PfamiPF00571. CBS. 1 hit.
    PF00478. IMPDH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000130. IMPDH. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiIMDH_TRIFO
    AccessioniPrimary (citable) accession number: P50097
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: November 2, 2016
    This is version 120 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)

    Miscellaneousi

    Miscellaneous

    Contains 2 potassium ions bound at each subunit interface. The second potassium binding site is not conserved and not observed in crystal structures of IMPDHs from other organisms (PubMed:12403633).1 Publication

    Keywords - Technical termi

    3D-structure

    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.