Application | Comment | Organism |
---|---|---|
drug development | IMPDH from Mycobacterium tuberculosis (MtIMPDH) is a potential molecular target to inhibitor development | Mycobacterium tuberculosis |
Cloned (Comment) | Organism |
---|---|
gene guaB2, recombinant expression in Escherichia coli strain C41(DE3) | Mycobacterium tuberculosis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
APAD+ | substrate inhibition, uncompetitive substrate inhibition versus IMP | Mycobacterium tuberculosis | |
additional information | several inhibitors compete with the flap for the vacant NADH site, thus preventing the hydrolysis of E-XMP* reaction intermediate | Mycobacterium tuberculosis | |
NAD+ | substrate inhibition | Mycobacterium tuberculosis | |
NADH | product inhibition, noncompetitive versus IMP, NAD+, and K+ | Mycobacterium tuberculosis | |
XMP | product inhibition, competitive versus IMP, noncompetitive versus NAD+ and K+ | Mycobacterium tuberculosis |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | steady-state kinetics and kinetic analysis, detailed overview | Mycobacterium tuberculosis | |
0.887 | - |
NAD+ | recombinant enzyme, pH 8.5, 37°C | Mycobacterium tuberculosis |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
K+ | required, activates, the enzyme contains one K+ per subunit | Mycobacterium tuberculosis | |
additional information | the enzyme activity is dependent on the presence of a monovalent cation, preferaby K+. Neither Na+ nor Li+, which have lower ionic radii than K+, activate the MtIMPDH. Divalent cations, such as Mg2+ and Ca2+, do not activate the enzyme even at 200 mM | Mycobacterium tuberculosis |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
54775 | - |
- |
Mycobacterium tuberculosis |
220000 | - |
about, molecular weight determination by cross-linking experiments and 12% SDS-PAGE analysis, since the enzyme elutes as different species depending on its concentration, indicating the presence of different aggregated forms | Mycobacterium tuberculosis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
IMP + NAD+ + H2O | Mycobacterium tuberculosis | - |
XMP + NADH + H+ | - |
? | |
IMP + NAD+ + H2O | Mycobacterium tuberculosis H37Rv | - |
XMP + NADH + H+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacterium tuberculosis | P9WKI7 | - |
- |
Mycobacterium tuberculosis H37Rv | P9WKI7 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant soluble enzyme 1.7fold from Escherichia coli strain C41(DE3) by affinity chromatography and gel filtration | Mycobacterium tuberculosis |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
IMP + NAD+ + H2O = XMP + NADH + H+ | a steady-state ordered Bi Bi kinetic mechanism in which IMP binds first followed by NAD+, and product release is ordered. Hydride transfer appears not to be rate-limiting. The pH-rate profile indicates one deprotonated group essential for catalysis | Mycobacterium tuberculosis |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
2 | - |
purified recombinant enzyme, pH 8.5, 37°C | Mycobacterium tuberculosis |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
IMP + APAD+ + H2O | - |
Mycobacterium tuberculosis | XMP + APADH + H+ | - |
? | |
IMP + APAD+ + H2O | - |
Mycobacterium tuberculosis H37Rv | XMP + APADH + H+ | - |
? | |
IMP + NAD+ + H2O | - |
Mycobacterium tuberculosis | XMP + NADH + H+ | - |
? | |
IMP + NAD+ + H2O | - |
Mycobacterium tuberculosis H37Rv | XMP + NADH + H+ | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | MtIMPDH predominates as a tetramer | Mycobacterium tuberculosis |
tetramer | 4 * 54775, mass spectrometry, x * 55000, recombinnat enzyme, SDS-PAGE, 4 * 54700, about, sequence calculation | Mycobacterium tuberculosis |
Synonyms | Comment | Organism |
---|---|---|
guaB2 | - |
Mycobacterium tuberculosis |
IMP dehydrogenase | - |
Mycobacterium tuberculosis |
IMPDH | - |
Mycobacterium tuberculosis |
inosine 5'-monophosphate dehydrogenase | - |
Mycobacterium tuberculosis |
Rv3411c | - |
Mycobacterium tuberculosis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Mycobacterium tuberculosis |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
3.1 | - |
NAD+ | recombinant enzyme, pH 8.5, 37°C | Mycobacterium tuberculosis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | 8.5 | - |
Mycobacterium tuberculosis |
pH Minimum | pH Maximum | Comment | Organism |
---|---|---|---|
7 | 10 | activity range, profile overview | Mycobacterium tuberculosis |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
3-acetylpyridine adenine dinucleotide | the NAD+ analog 3-acetylpyridine adenine dinucleotide (APAD+) is a substrate for MtIMPDH and the dependence of velocity on increasing concentrations of APAD+ (Fig. 4B) also displayed substrate inhibition | Mycobacterium tuberculosis | |
NAD+ | groups with pK values of 7.5 and 9.0 are important for NAD+ binding | Mycobacterium tuberculosis |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | inhibition kinetic analysis, detailed overview | Mycobacterium tuberculosis | |
6.3 | - |
NAD+ | recombinant enzyme, pH 8.5, 37°C | Mycobacterium tuberculosis |
General Information | Comment | Organism |
---|---|---|
malfunction | inhibition of IMPDH causes an overall reduction in guanine nucleotide pools and, as phosphoribosyl pyrophosphate (PRPP) synthetase and ribonucleotide reductase are allosterically regulated by these nucleotides, it may affect several metabolic pathways | Mycobacterium tuberculosis |