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Q8T6T2 (IMDH_CRYPV) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 72. 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
ORF Names:56k.02, cgd6_20
OrganismCryptosporidium parvum
Taxonomic identifier5807 [NCBI]
Taxonomic lineageEukaryotaAlveolataApicomplexaConoidasidaCoccidiaEucoccidioridaEimeriorinaCryptosporidiidaeCryptosporidium

Protein attributes

Sequence length400 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. Ref.4

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 By similarity. Resistant to mycophenolic acid (MPA) inhibition. Ref.4

Pathway

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

Subunit structure

Homotetramer. Ref.4

Subcellular location

Cytoplasm By similarity HAMAP-Rule MF_03156.

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.

Sequence similarities

Belongs to the IMPDH/GMPR family.

Biophysicochemical properties

Kinetic parameters:

KM=29 µM for Inosine 5'-phosphate Ref.4

KM=150 µM for NAD+

Ontologies

Keywords
   Biological processGMP biosynthesis
Purine biosynthesis
   Cellular componentCytoplasm
   LigandMetal-binding
NAD
Potassium
   Molecular functionOxidoreductase
   Technical term3D-structure
Direct protein sequencing
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

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

nucleotide binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 400400Inosine-5'-monophosphate dehydrogenase HAMAP-Rule MF_03156
PRO_0000415682

Regions

Nucleotide binding212 – 2143NAD By similarity
Region252 – 2543IMP binding By similarity
Region275 – 2762IMP binding By similarity
Region299 – 3035IMP binding By similarity

Sites

Active site2191Thioimidate intermediate By similarity
Metal binding2141Potassium; via carbonyl oxygen By similarity
Metal binding2161Potassium; via carbonyl oxygen By similarity
Metal binding2191Potassium; via carbonyl oxygen By similarity
Metal binding3831Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding3841Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding3851Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Binding site1631NAD By similarity
Binding site2171IMP By similarity
Binding site3291IMP By similarity

Secondary structure

................................................................... 400
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8T6T2 [UniParc].

Last modified June 1, 2002. Version 1.
Checksum: DAAF96B44050DD18

FASTA40043,081
        10         20         30         40         50         60 
MGTKNIGKGL TFEDILLVPN YSEVLPREVS LETKLTKNVS LKIPLISSAM DTVTEHLMAV 

        70         80         90        100        110        120 
GMARLGGIGI IHKNMDMESQ VNEVLKVKNW ISNLEKNEST PDQNLDKEST DGKDTKSNNN 

       130        140        150        160        170        180 
IDAYSNENLD NKGRLRVGAA IGVNEIERAK LLVEAGVDVI VLDSAHGHSL NIIRTLKEIK 

       190        200        210        220        230        240 
SKMNIDVIVG NVVTEEATKE LIENGADGIK VGIGPGSICT TRIVAGVGVP QITAIEKCSS 

       250        260        270        280        290        300 
VASKFGIPII ADGGIRYSGD IGKALAVGAS SVMIGSILAG TEESPGEKEL IGDTVYKYYR 

       310        320        330        340        350        360 
GMGSVGAMKS GSGDRYFQEK RPENKMVPEG IEGRVKYKGE MEGVVYQLVG GLRSCMGYLG 

       370        380        390        400 
SASIEELWKK SSYVEITTSG LRESHVHDVE IVKEVMNYSK 

« Hide

References

« Hide 'large scale' references
[1]"Genetic complementation in apicomplexan parasites."
Striepen B., White M.W., Li C., Guerini M.N., Malik S.B., Logsdon J.M. Jr., Liu C., Abrahamsen M.S.
Proc. Natl. Acad. Sci. U.S.A. 99:6304-6309(2002) [PubMed] [Europe PMC] [Abstract]
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).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3FFSX-ray3.19A/B/C/D1-400[»]
4IXHX-ray2.10A/B/C/D1-89[»]
A/B/C/D135-400[»]
ProteinModelPortalQ8T6T2.
SMRQ8T6T2. Positions 7-377.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ8T6T2.
ChEMBLCHEMBL6145.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayUPA00601; UER00295.

Family and domain databases

Gene3D3.20.20.70. 2 hits.
HAMAPMF_01964. IMPDH.
InterProIPR013785. Aldolase_TIM.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]
PfamPF00478. IMPDH. 1 hit.
[Graphical view]
PROSITEPS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8T6T2.

Entry information

Entry nameIMDH_CRYPV
AccessionPrimary (citable) accession number: Q8T6T2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 22, 2012
Last sequence update: June 1, 2002
Last modified: July 9, 2014
This is version 72 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