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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 Publication

Catalytic activityi

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH.UniRule annotation

Cofactori

Potassium By similarity.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 Publication

Kineticsi

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

Pathwayi

Sites

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

Regions

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

GO - Molecular functioni

  1. IMP dehydrogenase activity Source: UniProtKB-HAMAP
  2. adenyl nucleotide binding Source: InterPro
  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 dehydrogenase (EC:1.1.1.205)
Short name:
IMP dehydrogenase
Short name:
IMPD
Short name:
IMPDH
Gene namesi
Name:IMPDH
OrganismiTritrichomonas foetus (Trichomonas foetus) (Tritrichomonas suis)
Taxonomic identifieri56690 [NCBI]
Taxonomic lineageiEukaryotaParabasaliaTritrichomonadidaTritrichomonadidaeTritrichomonas

Subcellular locationi

Cytoplasm By similarity UniRule annotation

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
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 dehydrogenaseUniRule annotation
PRO_0000093676Add
BLAST

Interactioni

Subunit structurei

Homotetramer.

Structurei

Secondary structure

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.

Miscellaneous databases

EvolutionaryTraceiP50097.

Family & Domainsi

Domains and Repeats

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

Region

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

Sequence similaritiesi

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

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

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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: June 11, 2014
This is version 106 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 (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

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