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Protein

Inosine-5'-monophosphate dehydrogenase

Gene

56k.02

Organism
Cryptosporidium parvum
Status
Reviewed-Annotation score: Annotation score: 4 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.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 (By similarity). Resistant to mycophenolic acid (MPA) inhibition.1 PublicationUniRule annotation

Kineticsi

  1. KM=29 µM for Inosine 5'-phosphate1 Publication
  2. KM=150 µM for NAD+1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei163 – 1631NADUniRule annotation
Metal bindingi214 – 2141Potassium; via carbonyl oxygenUniRule annotation
Metal bindingi216 – 2161Potassium; via carbonyl oxygenUniRule annotation
Binding sitei217 – 2171IMPUniRule annotation
Active sitei219 – 2191Thioimidate intermediateUniRule annotation
Metal bindingi219 – 2191Potassium; via carbonyl oxygenUniRule annotation
Binding sitei329 – 3291IMPUniRule annotation
Metal bindingi383 – 3831Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
Metal bindingi384 – 3841Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
Metal bindingi385 – 3851Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi212 – 2143NADUniRule annotation

GO - Molecular functioni

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

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

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
ORF Names:56k.02, cgd6_20
OrganismiCryptosporidium parvum
Taxonomic identifieri5807 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaConoidasidaCoccidiaEucoccidioridaEimeriorinaCryptosporidiidaeCryptosporidium

Subcellular locationi

Cytoplasm UniRule annotation

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 400400Inosine-5'-monophosphate dehydrogenasePRO_0000415682Add
BLAST

Interactioni

Subunit structurei

Homotetramer.1 PublicationUniRule annotation

Structurei

Secondary structure

1
400
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 84Combined sources
Helixi12 – 143Combined sources
Beta strandi15 – 173Combined sources
Helixi26 – 283Combined sources
Beta strandi33 – 364Combined sources
Beta strandi39 – 479Combined sources
Turni51 – 533Combined sources
Helixi56 – 649Combined sources
Beta strandi68 – 714Combined sources
Beta strandi73 – 753Combined sources
Helixi77 – 8812Combined sources
Turni132 – 1343Combined sources
Beta strandi138 – 1414Combined sources
Helixi146 – 1549Combined sources
Beta strandi158 – 1636Combined sources
Beta strandi167 – 1693Combined sources
Helixi170 – 18213Combined sources
Beta strandi186 – 1927Combined sources
Helixi195 – 2039Combined sources
Beta strandi207 – 2115Combined sources
Helixi221 – 2244Combined sources
Helixi231 – 24515Combined sources
Beta strandi249 – 2535Combined sources
Helixi258 – 2669Combined sources
Beta strandi270 – 2756Combined sources
Helixi276 – 2794Combined sources
Beta strandi281 – 2844Combined sources
Beta strandi288 – 2914Combined sources
Beta strandi294 – 3007Combined sources
Helixi305 – 3095Combined sources
Beta strandi332 – 3365Combined sources
Helixi341 – 35818Combined sources
Helixi364 – 3707Combined sources
Beta strandi373 – 3753Combined sources
Helixi378 – 3847Combined sources
Beta strandi388 – 3914Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3FFSX-ray3.19A/B/C/D1-400[»]
4IXHX-ray2.10A/B/C/D1-89[»]
A/B/C/D135-400[»]
4QJ1X-ray2.42A/B/C/D1-400[»]
ProteinModelPortaliQ8T6T2.
SMRiQ8T6T2. Positions 7-377.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8T6T2.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni252 – 2543IMP bindingUniRule annotation
Regioni275 – 2762IMP bindingUniRule annotation
Regioni299 – 3035IMP bindingUniRule annotation

Sequence similaritiesi

Belongs to the IMPDH/GMPR family.UniRule annotation

Family and domain databases

Gene3Di3.20.20.70. 2 hits.
HAMAPiMF_01964. IMPDH.
InterProiIPR013785. Aldolase_TIM.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]
PfamiPF00478. IMPDH. 1 hit.
[Graphical view]
PROSITEiPS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8T6T2-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGTKNIGKGL TFEDILLVPN YSEVLPREVS LETKLTKNVS LKIPLISSAM
60 70 80 90 100
DTVTEHLMAV GMARLGGIGI IHKNMDMESQ VNEVLKVKNW ISNLEKNEST
110 120 130 140 150
PDQNLDKEST DGKDTKSNNN IDAYSNENLD NKGRLRVGAA IGVNEIERAK
160 170 180 190 200
LLVEAGVDVI VLDSAHGHSL NIIRTLKEIK SKMNIDVIVG NVVTEEATKE
210 220 230 240 250
LIENGADGIK VGIGPGSICT TRIVAGVGVP QITAIEKCSS VASKFGIPII
260 270 280 290 300
ADGGIRYSGD IGKALAVGAS SVMIGSILAG TEESPGEKEL IGDTVYKYYR
310 320 330 340 350
GMGSVGAMKS GSGDRYFQEK RPENKMVPEG IEGRVKYKGE MEGVVYQLVG
360 370 380 390 400
GLRSCMGYLG SASIEELWKK SSYVEITTSG LRESHVHDVE IVKEVMNYSK
Length:400
Mass (Da):43,081
Last modified:June 1, 2002 - v1
Checksum:iDAAF96B44050DD18
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF426177 Genomic DNA. Translation: AAL83208.1.
BX538350 Genomic DNA. Translation: CAD98604.1.
FX115298 mRNA. Translation: BAJ77401.1.
FX115945 mRNA. Translation: BAJ78048.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF426177 Genomic DNA. Translation: AAL83208.1.
BX538350 Genomic DNA. Translation: CAD98604.1.
FX115298 mRNA. Translation: BAJ77401.1.
FX115945 mRNA. Translation: BAJ78048.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3FFSX-ray3.19A/B/C/D1-400[»]
4IXHX-ray2.10A/B/C/D1-89[»]
A/B/C/D135-400[»]
4QJ1X-ray2.42A/B/C/D1-400[»]
ProteinModelPortaliQ8T6T2.
SMRiQ8T6T2. Positions 7-377.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiQ8T6T2.
ChEMBLiCHEMBL6145.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00601; UER00295.

Miscellaneous databases

EvolutionaryTraceiQ8T6T2.

Family and domain databases

Gene3Di3.20.20.70. 2 hits.
HAMAPiMF_01964. IMPDH.
InterProiIPR013785. Aldolase_TIM.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]
PfamiPF00478. IMPDH. 1 hit.
[Graphical view]
PROSITEiPS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: Iowa.
  2. "Integrated mapping, chromosomal sequencing and sequence analysis of Cryptosporidium parvum."
    Bankier A.T., Spriggs H.F., Fartmann B., Konfortov B.A., Madera M., Vogel C., Teichmann S.A., Ivens A., Dear P.H.
    Genome Res. 13:1787-1799(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Iowa.
  3. "Construction and analysis of full-length cDNA library of Cryptosporidium parvum."
    Yamagishi J., Wakaguri H., Sugano S., Kawano S., Fujisaki K., Sugimoto C., Watanabe J., Suzuki Y., Kimata I., Xuan X.
    Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: HNJ-1.
  4. "Cryptosporidium parvum IMP dehydrogenase: identification of functional, structural, and dynamic properties that can be exploited for drug design."
    Umejiego N.N., Li C., Riera T., Hedstrom L., Striepen B.
    J. Biol. Chem. 279:40320-40327(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-11, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ENZYME REGULATION.
  5. "The structural basis of Cryptosporidium-specific IMP dehydrogenase inhibitor selectivity."
    Macpherson I.S., Kirubakaran S., Gorla S.K., Riera T.V., D'Aquino J.A., Zhang M., Cuny G.D., Hedstrom L.
    J. Am. Chem. Soc. 132:1230-1231(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.19 ANGSTROMS).

Entry informationi

Entry nameiIMDH_CRYPV
AccessioniPrimary (citable) accession number: Q8T6T2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 22, 2012
Last sequence update: June 1, 2002
Last modified: January 7, 2015
This is version 76 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Miscellaneous

Cryptosporidium IMPDH was acquired through lateral transfer from eubacteria, and predictably the sensitivity to MPA differs from that of mammalian IMPDH forms. This divergence of parasite and host enzymes is exploited to design more potent parasite-specific inhibitors.

Keywords - Technical termi

3D-structure, Direct protein sequencing

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

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 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.