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P50097 (IMDH_TRIFO) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inosine-5'-monophosphate dehydrogenase

Short name=IMP dehydrogenase
Short name=IMPD
Short name=IMPDH
EC=1.1.1.205
Gene names
Name:IMPDH
OrganismTritrichomonas foetus (Trichomonas foetus) (Tritrichomonas suis)
Taxonomic identifier56690 [NCBI]
Taxonomic lineageEukaryotaParabasaliaTritrichomonadidaTritrichomonadidaeTritrichomonas

Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5

Catalytic activity

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH. HAMAP-Rule MF_03156

Cofactor

Potassium By similarity. HAMAP-Rule MF_03156

Enzyme regulation

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. Ref.3

Pathway

Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1. HAMAP-Rule MF_03156

Subunit structure

Homotetramer.

Subcellular location

Cytoplasm By similarity HAMAP-Rule MF_03156.

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 (Ref.8).

Sequence similarities

Belongs to the IMPDH/GMPR family.

Contains 2 CBS domains.

Biophysicochemical properties

Kinetic parameters:

KM=1.7 µM for Inosine 5'-phosphate Ref.5

KM=150 µM for NAD+

Ontologies

Keywords
   Biological processGMP biosynthesis
Purine biosynthesis
   Cellular componentCytoplasm
   DomainCBS domain
Repeat
   LigandMetal-binding
NAD
Potassium
   Molecular functionOxidoreductase
   Technical term3D-structure
Gene Ontology (GO)
   Biological_processGMP biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-HAMAP

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionIMP dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-HAMAP

adenyl nucleotide binding

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

nucleotide binding

Inferred from direct assay Ref.6. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 503503Inosine-5'-monophosphate dehydrogenase HAMAP-Rule MF_03156
PRO_0000093676

Regions

Domain103 – 16361CBS 1
Domain167 – 22862CBS 2
Nucleotide binding261 – 2633NAD HAMAP-Rule MF_03156
Nucleotide binding312 – 3143NAD HAMAP-Rule MF_03156
Region358 – 3603IMP binding HAMAP-Rule MF_03156
Region381 – 3822IMP binding HAMAP-Rule MF_03156
Region405 – 4095IMP binding HAMAP-Rule MF_03156

Sites

Active site3191Thioimidate intermediate Ref.9 Ref.10
Metal binding201Potassium 2; via carbonyl oxygen
Metal binding221Potassium 2
Metal binding2641Potassium 2; shared with tetrameric partner
Metal binding2661Potassium 2; via carbonyl oxygen; shared with tetrameric partner
Metal binding3141Potassium 1; via carbonyl oxygen
Metal binding3161Potassium 1; via carbonyl oxygen
Metal binding3191Potassium 1; via carbonyl oxygen
Metal binding4601Potassium 2; via carbonyl oxygen
Metal binding4851Potassium 1; via carbonyl oxygen; shared with tetrameric partner
Metal binding4861Potassium 1; via carbonyl oxygen; shared with tetrameric partner
Metal binding4871Potassium 1; via carbonyl oxygen; shared with tetrameric partner
Binding site3171IMP
Binding site4311IMP

Experimental info

Mutagenesis3191C → S: Has less than 0.06% of the wild-type activity. Ref.5

Secondary structure

.......................................................................... 503
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P50097 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: E204EADE7ECC4134

FASTA50355,473
        10         20         30         40         50         60 
MAKYYNEPCH TFNEYLLIPG LSTVDCIPSN VNLSTPLVKF QKGQQSEINL KIPLVSAIMQ 

        70         80         90        100        110        120 
SVSGEKMAIA LAREGGISFI FGSQSIESQA AMVHAVKNFK AGFVVSDSNV KPDQTFADVL 

       130        140        150        160        170        180 
AISQRTTHNT VAVTDDGTPH GVLLGLVTQR DYPIDLTQTE TKVSDMMTPF SKLVTAHQDT 

       190        200        210        220        230        240 
KLSEANKIIW EKKLNALPII DDDQHLRYIV FRKDYDRSQV CHNELVDSQK RYLVGAGINT 

       250        260        270        280        290        300 
RDFRERVPAL VEAGADVLCI DSSDGFSEWQ KITIGWIREK YGDKVKVGAG NIVDGEGFRY 

       310        320        330        340        350        360 
LADAGADFIK IGIGGGSICI TREQKGIGRG QATAVIDVVA ERNKYFEETG IYIPVCSDGG 

       370        380        390        400        410        420 
IVYDYHMTLA LAMGADFIML GRYFARFEES PTRKVTINGS VMKEYWGEGS SRARNWQRYD 

       430        440        450        460        470        480 
LGGKQKLSFE EGVDSYVPYA GKLKDNVEAS LNKVKSTMCN CGALTIPQLQ SKAKITLVSS 

       490        500 
VSIVEGGAHD VIVKDRINDY HPK 

« Hide

References

[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(+).

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L18917 Genomic DNA. Translation: AAB01581.1.
PIRA58910.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
DisProtDP00399.
ProteinModelPortalP50097.
SMRP50097. Positions 2-494.
ModBaseSearch...
MobiDBSearch...

Chemistry

DrugBankDB01024. Mycophenolic acid.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKP50097.
UniPathwayUPA00601; UER00295.

Family and domain databases

Gene3D3.20.20.70. 1 hit.
HAMAPMF_01964. IMPDH.
InterProIPR013785. Aldolase_TIM.
IPR000644. CBS_dom.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]
PANTHERPTHR11911:SF6. PTHR11911:SF6. 1 hit.
PfamPF00571. CBS. 2 hits.
PF00478. IMPDH. 1 hit.
[Graphical view]
PIRSFPIRSF000130. IMPDH. 1 hit.
SMARTSM00116. CBS. 2 hits.
[Graphical view]
PROSITEPS51371. CBS. 2 hits.
PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP50097.

Entry information

Entry nameIMDH_TRIFO
AccessionPrimary (citable) accession number: P50097
Entry history
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 statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways