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P0ADG7 (IMDH_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 82. 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:guaR
Ordered Locus Names:b2508, JW5401
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length488 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.11

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. IMP dehydrogenase subunit of E.coli contains a cysteine at the IMP binding site and is inhibited in a simple competitive manner by GMP. It does not exhibit allosteric properties as does IMP dehydrogenase from B.subtilis or S.typhimurium. Ref.11

Pathway

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

Subunit structure

Homotetramer. Ref.11

Domain

The CBS domain of IMPDH is a negative trans-regulator of adenylate nucleotide synthesis, and this role is independent of the catalytic function of IMPDH in the de novo GMP biosynthesis. Deletion of the CBS domain derepresses the synthesis of AMP from IMP. Ref.12 Ref.13

Sequence similarities

Belongs to the IMPDH/GMPR family.

Contains 2 CBS domains.

Biophysicochemical properties

Kinetic parameters:

KM=61 µM for Inosine 5'-phosphate Ref.11

KM=2000 µM for NAD+

KM=2.8 mM for K+

Sequence caution

The sequence CAA26133.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 488488Inosine-5'-monophosphate dehydrogenase HAMAP-Rule MF_01964
PRO_0000093695

Regions

Domain93 – 14957CBS 1
Domain153 – 21462CBS 2
Nucleotide binding248 – 2503NAD By similarity
Nucleotide binding298 – 3003NAD By similarity
Region338 – 3403IMP binding By similarity
Region361 – 3622IMP binding By similarity
Region385 – 3895IMP binding By similarity

Sites

Active site3051Thioimidate intermediate By similarity
Metal binding3001Potassium; via carbonyl oxygen By similarity
Metal binding3021Potassium; via carbonyl oxygen By similarity
Metal binding3051Potassium; via carbonyl oxygen By similarity
Metal binding4691Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding4701Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Metal binding4711Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity
Binding site2481NAD By similarity
Binding site3031IMP By similarity
Binding site4151IMP By similarity

Amino acid modifications

Modified residue2671N6-acetyllysine Ref.14
Modified residue4281N6-acetyllysine Ref.14

Experimental info

Mutagenesis131D → A: Causes a 38-fold increase in the value of Km for K(+). No change is observed in the value of Km for IMP. Ref.11
Mutagenesis501D → A: Causes a 17-fold increase in the value of Km for K(+). Ref.11
Mutagenesis541E → A: No effect. Ref.11
Mutagenesis1381D → A: No effect. Ref.11
Mutagenesis2001D → A: No effect. Ref.11
Mutagenesis2431D → A: No effect. Ref.11
Mutagenesis2481D → A: Causes a 130-fold decrease in the value of kcat. Ref.11
Mutagenesis3381D → A: Decreases the value of kcat by 600-fold. Increases the value of Km for IMP by 12-fold. Ref.11
Mutagenesis3691E → A: No effect. Ref.11
Mutagenesis3731E → A: No effect. Ref.11
Mutagenesis4691E → A: Increases the value of Km for K(+) by 17-fold. Ref.11
Sequence conflict2061R → A in CAA26133. Ref.1
Sequence conflict2061R → A in AAB18618. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P0ADG7 [UniParc].

Last modified December 6, 2005. Version 1.
Checksum: B0FD0A786779C98E

FASTA48852,022
        10         20         30         40         50         60 
MLRIAKEALT FDDVLLVPAH STVLPNTADL STQLTKTIRL NIPMLSAAMD TVTEARLAIA 

        70         80         90        100        110        120 
LAQEGGIGFI HKNMSIERQA EEVRRVKKHE SGVVTDPQTV LPTTTLREVK ELTERNGFAG 

       130        140        150        160        170        180 
YPVVTEENEL VGIITGRDVR FVTDLNQPVS VYMTPKERLV TVREGEAREV VLAKMHEKRV 

       190        200        210        220        230        240 
EKALVVDDEF HLIGMITVKD FQKAERKPNA CKDEQGRLRV GAAVGAGAGN EERVDALVAA 

       250        260        270        280        290        300 
GVDVLLIDSS HGHSEGVLQR IRETRAKYPD LQIIGGNVAT AAGARALAEA GCSAVKVGIG 

       310        320        330        340        350        360 
PGSICTTRIV TGVGVPQITA VADAVEALEG TGIPVIADGG IRFSGDIAKA IAAGASAVMV 

       370        380        390        400        410        420 
GSMLAGTEES PGEIELYQGR SYKSYRGMGS LGAMSKGSSD RYFQSDNAAD KLVPEGIEGR 

       430        440        450        460        470        480 
VAYKGRLKEI IHQQMGGLRS CMGLTGCGTI DELRTKAEFV RISGAGIQES HVHDVTITKE 


SPNYRLGS 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the guaB locus encoding IMP dehydrogenase of Escherichia coli K12."
Tiedeman A.A., Smith J.M.
Nucleic Acids Res. 13:1303-1316(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: K12.
[2]"Construction of a contiguous 874-kb sequence of the Escherichia coli-K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features."
Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T., Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K., Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T. expand/collapse author list , Oyama S., Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H., Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.
DNA Res. 4:91-113(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[3]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[4]"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]"Nucleotide sequence and organisation of the gua promoter region of Escherichia coli."
Thomas M.S., Drabble W.T.
Gene 36:45-53(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-96.
[6]"Regulation of the gua operon of Escherichia coli by the DnaA protein."
Tesfa-Selase F., Drabble W.T.
Mol. Gen. Genet. 231:256-264(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-90.
[7]"Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12."
Link A.J., Robison K., Church G.M.
Electrophoresis 18:1259-1313(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-12.
Strain: K12 / EMG2.
[8]Frutiger S., Hughes G.J., Pasquali C., Hochstrasser D.F.
Submitted (FEB-1996) to UniProtKB
Cited for: PARTIAL PROTEIN SEQUENCE OF 1-11.
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[9]"Extraction of membrane proteins by differential solubilization for separation using two-dimensional gel electrophoresis."
Molloy M.P., Herbert B.R., Walsh B.J., Tyler M.I., Traini M., Sanchez J.-C., Hochstrasser D.F., Williams K.L., Gooley A.A.
Electrophoresis 19:837-844(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-5.
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[10]"Protein identification with N and C-terminal sequence tags in proteome projects."
Wilkins M.R., Gasteiger E., Tonella L., Ou K., Tyler M., Sanchez J.-C., Gooley A.A., Walsh B.J., Bairoch A., Appel R.D., Williams K.L., Hochstrasser D.F.
J. Mol. Biol. 278:599-608(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-4.
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[11]"The roles of conserved carboxylate residues in IMP dehydrogenase and identification of a transition state analog."
Kerr K.M., Hedstrom L.
Biochemistry 36:13365-13373(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ENZYME REGULATION, MUTAGENESIS OF ASP-13; ASP-50; GLU-54; ASP-138; ASP-200; ASP-243; ASP-248; ASP-338; GLU-369; GLU-373 AND GLU-469.
Strain: K12.
[12]"The CBS subdomain of inosine 5'-monophosphate dehydrogenase regulates purine nucleotide turnover."
Pimkin M., Markham G.D.
Mol. Microbiol. 68:342-359(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN CBS.
Strain: K12 / BW25113.
[13]"A regulatory role of the Bateman domain of IMP dehydrogenase in adenylate nucleotide biosynthesis."
Pimkin M., Pimkina J., Markham G.D.
J. Biol. Chem. 284:7960-7969(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN CBS.
Strain: K12 / BW25113.
[14]"Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli."
Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F., Grishin N.V., Zhao Y.
Mol. Cell. Proteomics 8:215-225(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-267 AND LYS-428, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: K12 / JW1106 and K12 / MG1655 / ATCC 47076.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X02209 Genomic DNA. Translation: CAA26133.1. Different initiation.
U00096 Genomic DNA. Translation: AAC75561.1.
AP009048 Genomic DNA. Translation: BAA16395.2.
M10101 Genomic DNA. Translation: AAB18618.1.
PIRDEECIP. C65027.
RefSeqNP_417003.1. NC_000913.3.
YP_490736.1. NC_007779.1.

3D structure databases

ProteinModelPortalP0ADG7.
SMRP0ADG7. Positions 1-487.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid851324. 1 interaction.
DIPDIP-36207N.
IntActP0ADG7. 1 interaction.
MINTMINT-1235980.
STRING511145.b2508.

Chemistry

BindingDBP0ADG7.
ChEMBLCHEMBL3630.

2D gel databases

SWISS-2DPAGEP0ADG7.

Proteomic databases

PaxDbP0ADG7.
PRIDEP0ADG7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC75561; AAC75561; b2508.
BAA16395; BAA16395; BAA16395.
GeneID12934227.
946985.
KEGGecj:Y75_p2461.
eco:b2508.
PATRIC32120407. VBIEscCol129921_2606.

Organism-specific databases

EchoBASEEB0416.
EcoGeneEG10421. guaB.

Phylogenomic databases

eggNOGCOG0517.
HOGENOMHOG000165755.
KOK00088.
OMASSMGYCG.
OrthoDBEOG6GTZPV.
PhylomeDBP0ADG7.
ProtClustDBPRK05567.

Enzyme and pathway databases

BioCycEcoCyc:IMP-DEHYDROG-MONOMER.
ECOL316407:JW5401-MONOMER.
MetaCyc:IMP-DEHYDROG-MONOMER.
UniPathwayUPA00601; UER00295.

Gene expression databases

GenevestigatorP0ADG7.

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

PROP0ADG7.

Entry information

Entry nameIMDH_ECOLI
AccessionPrimary (citable) accession number: P0ADG7
Secondary accession number(s): P06981, P76574, P78202
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: December 6, 2005
Last modified: April 16, 2014
This is version 82 of the entry and version 1 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene