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P0C0H6 (IMDH_STRPY) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 57. 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:guaB
Synonyms:impD
OrganismStreptococcus pyogenes
Taxonomic identifier1314 [NCBI]
Taxonomic lineageBacteriaFirmicutesBacilliLactobacillalesStreptococcaceaeStreptococcus

Protein attributes

Sequence length493 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
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 By similarity. HAMAP-Rule MF_01964

Catalytic activity

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH. HAMAP-Rule MF_01964

Cofactor

Potassium By similarity. HAMAP-Rule MF_01964

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. HAMAP-Rule MF_01964

Pathway

Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1. HAMAP-Rule MF_01964

Subunit structure

Homotetramer. Ref.2

Sequence similarities

Belongs to the IMPDH/GMPR family.

Contains 2 CBS domains.

Biophysicochemical properties

Kinetic parameters:

KM=62 µM for Inosine 5'-phosphate Ref.2

KM=1180 µM for NAD+

pH dependence:

Optimum pH is 7.8.

Mass spectrometry

Molecular mass is 52328 Da from positions 2 - 493. Determined by MALDI. Ref.2

Ontologies

Keywords
   Biological processGMP biosynthesis
Purine biosynthesis
   DomainCBS domain
Repeat
   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

   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

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2
Chain2 – 493492Inosine-5'-monophosphate dehydrogenase HAMAP-Rule MF_01964
PRO_0000093714

Regions

Domain97 – 15559CBS 1
Domain159 – 21961CBS 2
Nucleotide binding303 – 3053NAD By similarity
Region343 – 3453IMP binding HAMAP-Rule MF_01964
Region366 – 3672IMP binding HAMAP-Rule MF_01964
Region390 – 3945IMP binding HAMAP-Rule MF_01964

Sites

Active site3101Thioimidate intermediate By similarity
Metal binding3051Potassium; via carbonyl oxygen By similarity
Metal binding3071Potassium; via carbonyl oxygen By similarity
Metal binding3101Potassium; via carbonyl oxygen By similarity
Metal binding4751Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding4761Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding4771Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Binding site2531NAD By similarity
Binding site3081IMP
Binding site4211IMP By similarity

Experimental info

Mutagenesis4061R → A: No activity. Ref.2
Mutagenesis4211E → Q: No activity. Ref.2
Mutagenesis4501Y → A: No effect. Ref.2
Mutagenesis4501Y → D: Reduces activity by 75%. Ref.2
Sequence conflict4191V → L no nucleotide entry Ref.2

Secondary structure

...................................................................................... 493
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P0C0H6 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 9C317AD598CB5740

FASTA49352,807
        10         20         30         40         50         60 
MSNWDTKFLK KGYTFDDVLL IPAESHVLPN EVDLKTKLAD NLTLNIPIIT AAMDTVTGSK 

        70         80         90        100        110        120 
MAIAIARAGG LGVIHKNMSI TEQAEEVRKV KRSENGVIID PFFLTPEHKV SEAEELMQRY 

       130        140        150        160        170        180 
RISGVPIVET LANRKLVGII TNRDMRFISD YNAPISEHMT SEHLVTAAVG TDLETAERIL 

       190        200        210        220        230        240 
HEHRIEKLPL VDNSGRLSGL ITIKDIEKVI EFPHAAKDEF GRLLVAAAVG VTSDTFERAE 

       250        260        270        280        290        300 
ALFEAGADAI VIDTAHGHSA GVLRKIAEIR AHFPNRTLIA GNIATAEGAR ALYDAGVDVV 

       310        320        330        340        350        360 
KVGIGPGSIC TTRVVAGVGV PQVTAIYDAA AVAREYGKTI IADGGIKYSG DIVKALAAGG 

       370        380        390        400        410        420 
NAVMLGSMFA GTDEAPGETE IYQGRKFKTY RGMGSIAAMK KGSSDRYFQG SVNEANKLVP 

       430        440        450        460        470        480 
EGIEGRVAYK GAASDIVFQM LGGIRSGMGY VGAGDIQELH ENAQFVEMSG AGLIESHPHD 

       490 
VQITNEAPNY SVH 

« Hide

References

[1]"Cloning, sequence analysis and expression of the group A streptococcal guaB gene encoding inosine monophosphate dehydrogenase."
Ashbaugh C.D., Wessels M.R.
Gene 165:57-60(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase."
Zhang R.G., Evans G., Rotella F.J., Westbrook E.M., Beno D., Huberman E., Joachimiak A., Collart F.R.
Biochemistry 38:4691-4700(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-20, X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH IMP, BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, SUBUNIT, MUTAGENESIS OF ARG-406; GLU-421 AND TYR-450.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U26056 Genomic DNA. Translation: AAB03846.1.
PIRJC4372.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZFJX-ray1.90A2-492[»]
ProteinModelPortalP0C0H6.
SMRP0C0H6. Positions 2-491.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP0C0H6.

Proteomic databases

PRIDEP0C0H6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

eggNOGCOG0517.

Enzyme and pathway databases

SABIO-RKP0C0H6.
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]
TIGRFAMsTIGR01302. IMP_dehydrog. 1 hit.
PROSITEPS51371. CBS. 2 hits.
PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP0C0H6.

Entry information

Entry nameIMDH_STRPY
AccessionPrimary (citable) accession number: P0C0H6
Secondary accession number(s): P50099, P68838
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: January 23, 2007
Last modified: February 19, 2014
This is version 57 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

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