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Information on EC 1.1.1.205 - IMP dehydrogenase and Organism(s) Pseudomonas aeruginosa and UniProt Accession Q9HXM5
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1.1.1.205 IMP dehydrogenaseIUBMB Comments
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
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Word Map
- 1.1.1.205
-
mycophenolic
- purine
- guanine
- mofetil
- ribavirin
- leukemia
- tiazofurin
-
rejection
- xmp
-
pharmacodynamic
-
salvage
- hypoxanthine
-
cyclosporine
-
allograft
-
prodrugs
- mizoribine
- phosphoribosyltransferase
- ribonucleotide
- xanthosine
-
guanylate
- tad
- calcineurin
- dgtp
- adenylosuccinate
- 6-mercaptopurine
- dihydrofolate
-
hypoxanthine-guanine
- cryptosporidium
- tacrolimus
- thiopurine
- riboside
- azathioprine
- glucuronide
- parvum
- benzamide
- pigmentosa
- sirolimus
- 6-thioguanine
- analysis
- rbv
-
amido
- cryptosporidiosis
-
c-nucleoside
- tritrichomonas
-
enteric-coated
-
predose
- hgprt
- pharmacology
- diagnostics
- drug development
- medicine
The taxonomic range for the selected organisms is: Pseudomonas aeruginosa
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
impdh, imp dehydrogenase, inosine monophosphate dehydrogenase, impdh2, impdh1, inosine 5'-monophosphate dehydrogenase, inosine-5'-monophosphate dehydrogenase, impdh ii, imp dh, inosinate dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dehydrogenase, inosinate
-
-
-
-
IMP dehydrogenase
-
-
-
-
IMP oxidoreductase
-
-
-
-
IMPD
-
-
-
-
IMPDH
-
-
-
-
inosinate dehydrogenase
-
-
-
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inosine 5'-monophosphate dehydrogenase
-
-
-
-
inosine monophosphate dehydrogenase
-
-
-
-
inosine monophosphate oxidoreductase
-
-
-
-
inosine-5'-phosphate dehydrogenase
-
-
-
-
inosinic acid dehydrogenase
-
-
-
-
Raspberry protein
-
-
-
-
SOI12
-
-
-
-
Superoxide-inducible protein 12
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
IMP:NAD+ oxidoreductase
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
CAS REGISTRY NUMBER
COMMENTARY
9028-93-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
MgATP2-
allosteric regulation of Pseudomonas aeruginosa IMPDH by MgATP2-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5S)-7-amino-5-(4-chlorophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile
F2K
3-(4-chlorophenyl)-4-(4-ethoxyphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
-
4-(3-bromo-4-methoxyphenyl)-3-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
-
4-(4-acetamidophenyl)-3-(4-chlorophenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
-
4-(4-acetamidophenyl)-3-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
-
4-(5-bromo-2-fluorophenyl)-3-(4-chlorophenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
-
4-(5-bromo-2-methoxyphenyl)-3-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
-
4-acetyl-N-(3-chloro-4-fluorophenyl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide
-
7-amino-5-(4-chlorophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile
-
7-amino-5-(4-nitrophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile
-
7-amino-5-(5-nitrothiophen-2-yl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile
-
N-[4-(1-benzyl-2,4,6-trioxo-2,3,4,5,6,11-hexahydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidin-5-yl)phenyl]acetamide
-
tetrasodium 6,6'-[(3,3'-dimethoxy[1,1'-biphenyl]-4,4'-diyl)bis[(E)-diazene-2,1-diyl]]bis(4-amino-5-hydroxynaphthalene-1,3-disulfonate)
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
MgATP2-
allosteric regulation of Pseudomonas aeruginosa IMPDH by MgATP2-. The the ATP-binding sites are located within the two CBS motifs. The compound acts as a positive effector increasing the catalytic activity of the wild-type enzyme, and also of the D199N variant, influencing both the maximal rate and the affinity for IMP, and showing a cooperativity effect for IMP, that is lost in mutant D199N
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0183
3-(4-chlorophenyl)-4-(4-ethoxyphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.0117
4-(3-bromo-4-methoxyphenyl)-3-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.019
4-(4-acetamidophenyl)-3-(4-chlorophenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.023
4-(4-acetamidophenyl)-3-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.0074
4-(5-bromo-2-fluorophenyl)-3-(4-chlorophenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.0117
4-(5-bromo-2-methoxyphenyl)-3-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.017
4-acetyl-N-(3-chloro-4-fluorophenyl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.004
7-amino-5-(4-chlorophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.007
7-amino-5-(4-nitrophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.004
7-amino-5-(5-nitrothiophen-2-yl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitrile
Pseudomonas aeruginosa
pH and temperature not specified in the publication
0.0028
N-[4-(1-benzyl-2,4,6-trioxo-2,3,4,5,6,11-hexahydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidin-5-yl)phenyl]acetamide
Pseudomonas aeruginosa
pH and temperature not specified in the publication
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
the key metabolic enzyme inosine-50-monophosphate dehydrogenase (IMPDH) occupies a central role in the de novo synthesis of guanosine nucleotides. The binding of Mg-ATP to Pseudomonas aeruginosa IMPDH and its crucial role in the regulation of the catalytic activity of the enzyme and its quaternary structure
additional information
additional information
three conserved loops seem to be key players in the allosteric regulation of enzyme activity as they connect the tetramer-tetramer interface with the active site and show significant modification upon substrate binding, mechanism for the allosteric regulation of IMPDH through the CBS motifs. Conerved residue Asp199 is involved in the recognition of the ribose moiety of ATP in IMPDHpa. Structure analysis of wild-type and mutant enzymes, overview
additional information
-
three conserved loops seem to be key players in the allosteric regulation of enzyme activity as they connect the tetramer-tetramer interface with the active site and show significant modification upon substrate binding, mechanism for the allosteric regulation of IMPDH through the CBS motifs. Conerved residue Asp199 is involved in the recognition of the ribose moiety of ATP in IMPDHpa. Structure analysis of wild-type and mutant enzymes, overview
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
IMPDHs share a two-domain organization composed of a catalytic domain and a smaller flanking domain containing two CBS motifs
additional information
-
IMPDHs share a two-domain organization composed of a catalytic domain and a smaller flanking domain containing two CBS motifs
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
apoenzyme and enzyme in complex with 18, hanging drop vapor diffusion method, using 500 mM lithium chloride, 50 mM ammonium sulfate and 8% (w/v) PEG 8000
purified recombinant IMPDH enzyme mutant DELTACBS in the apo form and in complex with IMP, sitting drop vapour diffusion method, mixing of 0.0015 ml of 9.2 mg/ml protein in 20 mM potassium phosphate, pH 8.0, 25 mM KCl, with 0.0015 ml reservoir solution consisting of either 4.3 M sodium chloride, 100 mM HEPES, pH 7.5, or 10 mM sodium citrate, and 33% PEG 8000 for the apoenzyme and containing 1.26 M ammonium sulfate, 100 mM HEPES, pH 7.5, for the IMP-complexed enzyme, equilibration against 0.15 ml or reservoir solution. For the D199N variant in complex with IMP, the optimized crystals are obtained by mixing 0.0015 ml of 11.7 mg/ml protein in solution in 20 mM potassium phosphate, pH 8.0, 25 mM KCl, and 10 mM IMP, with 0.0015 ml of reservoir solution containing 10% w/v PEG 4000, 200 mM magnesium chloride, 100 mM MES pH 6.5, and equilibration against 0.15 ml or reservoir solution, 18°C, X-ray diffraction structure determination and analysis at 1.65-1.95 A resolution, molecular replacement using a previously solved structure of wild-type IMPDHpa, PDB ID 4dqw, as a template
to 2.25 A resolution. Structure is a homotetramer of subunits dominated by a (beta/alpha)8-barrel fold. The cystathionine beta-synthase domains, residues 92-204, are not present in the model owing to disorder. A loop that creates part of the active site is composed of residues 297-315, links alpha8 and beta9 and carries the catalytic Cys304
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of a mutant lacking the CBS domains, IMPDH mutant DELTACBS. The DELTACBS variant lacks the CBS motifs from Ala92 to Lys202 of the full-length enzyme. This variant is fully active and its kinetic parameters are similar to those of wild-type IMPDHpa in the presence of its positive effector Mg-ATP. The catalytic activity of the D199N variant is still sensitive to Mg-ATP, influencing both the maximal rate and the affinity for IMP, but the cooperativity effect for IMP is lost
additional information
-
construction of a mutant lacking the CBS domains, IMPDH mutant DELTACBS. The DELTACBS variant lacks the CBS motifs from Ala92 to Lys202 of the full-length enzyme. This variant is fully active and its kinetic parameters are similar to those of wild-type IMPDHpa in the presence of its positive effector Mg-ATP. The catalytic activity of the D199N variant is still sensitive to Mg-ATP, influencing both the maximal rate and the affinity for IMP, but the cooperativity effect for IMP is lost
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant enzymes from Escherichia coli by affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene guaB, sequence comparisons, recombinant expression of wild-type and mutant enzymes in Escherichia coli
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rao, V.A.; Shepherd, S.M.; Owen, R.; Hunter, W.N.
Structure of Pseudomonas aeruginosa inosine 5-monophosphate dehydrogenase
Acta Crystallogr. Sect. F
69
243-247
2013
Pseudomonas aeruginosa (Q9HXM5), Pseudomonas aeruginosa
Labesse, G.; Alexandre, T.; Gelin, M.; Haouz, A.; Munier-Lehmann, H.
Crystallographic studies of two variants of Pseudomonas aeruginosa IMPDH with impaired allosteric regulation
Acta Crystallogr. Sect. D
71
1890-1899
2015
Pseudomonas aeruginosa (Q9HXM5), Pseudomonas aeruginosa
Alexandre, T.; Lupan, A.; Helynck, O.; Vichier-Guerre, S.; Dugue, L.; Gelin, M.; Haouz, A.; Labesse, G.; Munier-Lehmann, H.
First-in-class allosteric inhibitors of bacterial IMPDHs
Eur. J. Med. Chem.
167
124-132
2019
Eremothecium gossypii, Pseudomonas aeruginosa (Q9HXM5)
Juvale, K.; Shaik, A.; Kirubakaran, S.
Inhibitors of inosine 5'-monophosphate dehydrogenase as emerging new generation antimicrobial agents
MedChemComm
10
1290-1301
2019
Bacillus anthracis, Bacillus anthracis (A0A6L8P2U9), Cryptosporidium parvum, Clostridium perfringens (A0A127ELD1), Campylobacter jejuni (A0A2R4D3F6), Mycolicibacterium thermoresistibile (G7CNL4), Mycobacterium tuberculosis (P9WKI7), Listeria monocytogenes (Q926Y9), Pseudomonas aeruginosa (Q9HXM5), Vibrio cholerae (Q9KTW3), Bacillus anthracis Ames, Mycolicibacterium thermoresistibile ATCC 19527 (G7CNL4), Listeria monocytogenes ATCC BAA-679 (Q926Y9), Mycobacterium tuberculosis H37Rv (P9WKI7), Vibrio cholerae ATCC 39315 (Q9KTW3)
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