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P50097

- IMDH_TRIFO

UniProt

P50097 - IMDH_TRIFO

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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

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

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.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
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

  1. cytoplasm Source: UniProtKB-HAMAP
Complete GO annotation...

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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

        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 .
PIRi A58910.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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...

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: November 26, 2014
This is version 109 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