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P50097

- IMDH_TRIFO

UniProt

P50097 - IMDH_TRIFO

Protein

Inosine-5'-monophosphate dehydrogenase

Gene

IMPDH

Organism
Tritrichomonas foetus (Trichomonas foetus) (Tritrichomonas suis)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      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. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism.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.1 PublicationUniRule annotation

    Kineticsi

    1. KM=1.7 µM for Inosine 5'-phosphate1 Publication
    2. KM=150 µM for NAD+1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi20 – 201Potassium 2; via carbonyl oxygen1 Publication
    Metal bindingi22 – 221Potassium 21 Publication
    Metal bindingi264 – 2641Potassium 2; shared with tetrameric partner1 Publication
    Metal bindingi266 – 2661Potassium 2; via carbonyl oxygen; shared with tetrameric partner1 Publication
    Metal bindingi314 – 3141Potassium 1; via carbonyl oxygen1 Publication
    Metal bindingi316 – 3161Potassium 1; via carbonyl oxygen1 Publication
    Binding sitei317 – 3171IMP
    Active sitei319 – 3191Thioimidate intermediate2 PublicationsUniRule annotation
    Metal bindingi319 – 3191Potassium 1; via carbonyl oxygen1 Publication
    Binding sitei431 – 4311IMP
    Metal bindingi460 – 4601Potassium 2; via carbonyl oxygen1 Publication
    Metal bindingi485 – 4851Potassium 1; via carbonyl oxygen; shared with tetrameric partner1 Publication
    Metal bindingi486 – 4861Potassium 1; via carbonyl oxygen; shared with tetrameric partner1 Publication
    Metal bindingi487 – 4871Potassium 1; via carbonyl oxygen; shared with tetrameric partner1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi261 – 2633NAD
    Nucleotide bindingi312 – 3143NAD

    GO - Molecular functioni

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

    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

    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

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi319 – 3191C → S: Has less than 0.06% of the wild-type activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 503503Inosine-5'-monophosphate dehydrogenasePRO_0000093676Add
    BLAST

    Interactioni

    Subunit structurei

    Homotetramer.4 PublicationsUniRule annotation

    Structurei

    Secondary structure

    1
    503
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi12 – 143
    Beta strandi15 – 173
    Helixi28 – 303
    Beta strandi49 – 568
    Turni60 – 623
    Helixi65 – 739
    Beta strandi77 – 804
    Beta strandi82 – 843
    Helixi86 – 9712
    Turni98 – 1003
    Beta strandi235 – 2384
    Beta strandi240 – 2423
    Helixi243 – 25311
    Beta strandi256 – 2605
    Helixi268 – 28114
    Helixi282 – 2843
    Beta strandi287 – 2926
    Helixi295 – 30410
    Beta strandi307 – 3115
    Helixi317 – 3215
    Turni322 – 3254
    Helixi331 – 34919
    Beta strandi350 – 3523
    Beta strandi355 – 3595
    Helixi364 – 3729
    Beta strandi376 – 3816
    Helixi382 – 3854
    Beta strandi390 – 3923
    Beta strandi394 – 3974
    Beta strandi400 – 4067
    Helixi411 – 4144
    Helixi416 – 4194
    Beta strandi421 – 4233
    Beta strandi434 – 4385
    Helixi443 – 46018
    Helixi466 – 4727
    Beta strandi475 – 4773
    Turni480 – 4823
    Turni484 – 4863
    Beta strandi490 – 4934

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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. Positions 2-494.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP50097.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini103 – 16361CBS 1UniRule annotationAdd
    BLAST
    Domaini167 – 22862CBS 2UniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni358 – 3603IMP binding
    Regioni381 – 3822IMP binding
    Regioni405 – 4095IMP binding

    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

    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]
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P50097-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAKYYNEPCH TFNEYLLIPG LSTVDCIPSN VNLSTPLVKF QKGQQSEINL    50
    KIPLVSAIMQ SVSGEKMAIA LAREGGISFI FGSQSIESQA AMVHAVKNFK 100
    AGFVVSDSNV KPDQTFADVL AISQRTTHNT VAVTDDGTPH GVLLGLVTQR 150
    DYPIDLTQTE TKVSDMMTPF SKLVTAHQDT KLSEANKIIW EKKLNALPII 200
    DDDQHLRYIV FRKDYDRSQV CHNELVDSQK RYLVGAGINT RDFRERVPAL 250
    VEAGADVLCI DSSDGFSEWQ KITIGWIREK YGDKVKVGAG NIVDGEGFRY 300
    LADAGADFIK IGIGGGSICI TREQKGIGRG QATAVIDVVA ERNKYFEETG 350
    IYIPVCSDGG IVYDYHMTLA LAMGADFIML GRYFARFEES PTRKVTINGS 400
    VMKEYWGEGS SRARNWQRYD LGGKQKLSFE EGVDSYVPYA GKLKDNVEAS 450
    LNKVKSTMCN CGALTIPQLQ SKAKITLVSS VSIVEGGAHD VIVKDRINDY 500
    HPK 503
    Length:503
    Mass (Da):55,473
    Last modified:October 1, 1996 - v1
    Checksum:iE204EADE7ECC4134
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L18917 Genomic DNA. Translation: AAB01581.1.
    PIRiA58910.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L18917 Genomic DNA. Translation: AAB01581.1 .
    PIRi A58910.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AK5 X-ray 2.30 A 1-503 [» ]
    1LRT X-ray 2.20 A/B/C/D 2-503 [» ]
    1ME7 X-ray 2.15 A 1-503 [» ]
    1ME8 X-ray 1.90 A 1-503 [» ]
    1ME9 X-ray 2.20 A 1-503 [» ]
    1MEH X-ray 1.95 A 1-503 [» ]
    1MEI X-ray 2.20 A 1-503 [» ]
    1MEW X-ray 2.15 A 1-503 [» ]
    1PVN X-ray 2.00 A/B/C/D 2-503 [» ]
    DisProti DP00399.
    ProteinModelPortali P50097.
    SMRi P50097. Positions 2-494.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    DrugBanki DB01024. Mycophenolic acid.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Enzyme and pathway databases

    UniPathwayi UPA00601 ; UER00295 .
    SABIO-RK P50097.

    Miscellaneous databases

    EvolutionaryTracei P50097.

    Family and domain databases

    Gene3Di 3.20.20.70. 1 hit.
    HAMAPi MF_01964. IMPDH.
    InterProi IPR013785. Aldolase_TIM.
    IPR000644. CBS_dom.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view ]
    PANTHERi PTHR11911:SF6. PTHR11911:SF6. 1 hit.
    Pfami PF00571. CBS. 2 hits.
    PF00478. IMPDH. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000130. IMPDH. 1 hit.
    SMARTi SM00116. CBS. 2 hits.
    [Graphical view ]
    PROSITEi PS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning, sequencing, and structural analysis of the DNA encoding inosine monophosphate dehydrogenase (EC 1.1.1.205) from Tritrichomonas foetus."
      Beck J.T., Zhao S., Wang C.C.
      Exp. Parasitol. 78:101-112(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: UNK.
    2. Wang C.C.
      Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    3. "A novel mechanism of mycophenolic acid resistance in the protozoan parasite Tritrichomonas foetus."
      Hedstrom L., Cheung K.S., Wang C.C.
      Biochem. Pharmacol. 39:151-160(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    4. "Identification of the IMP binding site in the IMP dehydrogenase from Tritrichomonas foetus."
      Huete-Perez J.A., Wu J.C., Whitby F.G., Wang C.C.
      Biochemistry 34:13889-13894(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION.
    5. "Kinetic mechanism of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase."
      Digits J.A., Hedstrom L.
      Biochemistry 38:2295-2306(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-319.
    6. "Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo."
      McLean J.E., Hamaguchi N., Belenky P., Mortimer S.E., Stanton M., Hedstrom L.
      Biochem. J. 379:243-251(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEIC ACID-BINDING.
    7. "Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex."
      Whitby F.G., Luecke H., Kuhn P., Somoza J.R., Huete-Perez J.A., Phillips J.D., Hill C.P., Fletterick R.J., Wang C.C.
      Biochemistry 36:10666-10674(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
    8. "Crystal structure of a ternary complex of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase: NAD+ orients the active site loop for catalysis."
      Gan L., Petsko G.A., Hedstrom L.
      Biochemistry 41:13309-13317(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 4-377 IN COMPLEX WITH SUBSTRATE AND INHIBITOR, POTASSIUM-BINDING.
    9. "Crystal structure of Tritrichomonas foetus inosine monophosphate dehydrogenase in complex with the inhibitor ribavirin monophosphate reveals a catalysis-dependent ion-binding site."
      Prosise G.L., Wu J.Z., Luecke H.
      J. Biol. Chem. 277:50654-50659(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH INHIBITOR, ACTIVE SITE.
    10. "The immunosuppressive agent mizoribine monophosphate forms a transition state analogue complex with inosine monophosphate dehydrogenase."
      Gan L., Seyedsayamdost M.R., Shuto S., Matsuda A., Petsko G.A., Hedstrom L.
      Biochemistry 42:857-863(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 4-377 IN COMPLEX WITH INHIBITOR (MIZORIBINE MONOPHOSPHATE; MZP) AND POTASSIUM, ACTIVE SITE.
    11. "Crystal structures of Tritrichomonas foetus inosine monophosphate dehydrogenase in complex with substrate, cofactor and analogs: a structural basis for the random-in ordered-out kinetic mechanism."
      Prosise G.L., Luecke H.
      J. Mol. Biol. 326:517-527(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-483 IN COMPLEX WITH SUBSTRATE; PRODUCT; INHIBITOR (MYCOPHENOLIC ACID; MPA) AND NAD(+).

    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: October 1, 2014
    This is version 107 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

    External Data

    Dasty 3