Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a potential therapeutic target, and the NAD+ site may be an exploitable target for the design of antimicrobial drugs | Tritrichomonas suis |
Cloned (Comment) | Organism |
---|---|
expression of the full-length enzyme and the alphabeta core domain of the enzyme in Escherichia coli | Tritrichomonas suis |
Crystallization (Comment) | Organism |
---|---|
purified recombinant full-length enzyme and alphabeta core domain in complex with inosine 5'-phosphate and beta-methylene-thiazole-4-carboxamide adenine dinucleotide, X-ray diffraction structure determination and analysis at 2.2 A resolution, molecular replacement | Tritrichomonas suis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
beta-methylene-thiazole-4-carboxamide adenine dinucleotide | i.e. beta-Me-TAD, enzyme binding structure analysis, the enzyme active site loop is ordered in this complex, and the catalytic Cys319 is 3.6 A from IMP, in the same plane as the hypoxanthine ring, the active site loop forms hydrogen bonds to the carboxamide of beta-Me-TAD, overview | Tritrichomonas suis | |
additional information | structural basis of the drug selectivity, overview | Tritrichomonas suis | |
Mycophenolic acid | i.e. MPA, slight inhibition, microbial IMPDHs differ from mammalian enzymes in their lower affinity for inhibitors such as mycophenolic acid and thiazole-4-carboxamide adenine dinucleotide, part of this resistance is determined by the coupling between nicotinamide and adenosine subsites in the NAD+ binding site that is postulated to involve an active site flap | Tritrichomonas suis | |
NAD+ | - |
Tritrichomonas suis | |
thiazole-4-carboxamide adenine dinucleotide | i.e. TAD, slight inhibition, microbial IMPDHs differ from mammalian enzymes in their lower affinity for inhibitors such as mycophenolic acid and thiazole-4-carboxamide adenine dinucleotide, part of this resistance is determined by the coupling between nicotinamide and adenosine subsites in the NAD+ binding site that is postulated to involve an active site flap | Tritrichomonas suis |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0017 | - |
inosine 5'-phosphate | pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl | Tritrichomonas suis | |
0.0024 | - |
inosine 5'-phosphate | pH 8.0, 25°C, recombinant alphabeta core domain, in absence of 100 mM KCl | Tritrichomonas suis | |
0.0026 | - |
inosine 5'-phosphate | pH 8.0, 25°C, recombinant full-length enzyme, in absence of 100 mM KCl | Tritrichomonas suis | |
0.003 | - |
inosine 5'-phosphate | pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl | Tritrichomonas suis | |
0.11 | - |
NAD+ | pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl | Tritrichomonas suis | |
0.15 | - |
NAD+ | pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl | Tritrichomonas suis | |
1.1 | - |
NAD+ | pH 8.0, 25°C, recombinant full-length enzyme, in absence of 100 mM KCl | Tritrichomonas suis | |
1.2 | - |
NAD+ | pH 8.0, 25°C, recombinant alphabeta core domain, in absence of 100 mM KCl | Tritrichomonas suis |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
K+ | strong activation, the K+ site is observed at the subunit interface, the activation is linked to NAD+ | Tritrichomonas suis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
inosine 5'-phosphate + NAD+ + H2O | Tritrichomonas suis | rate-limiting step of the de novo guanine nucleotide biosynthesis | xanthosine 5'-phosphate + NADH | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Tritrichomonas suis | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant full-length enzyme and alphabeta core domain of the enzyme from Escherichia coli | Tritrichomonas suis |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
IMP + NAD+ + H2O = XMP + NADH + H+ | substrate binding and catalytic reaction mechanism, Cys319 is the catalytic residue, NAD+ promotes the nucleophilic attack of Cys319 on IMP | Tritrichomonas suis |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
inosine 5'-phosphate + NAD+ + H2O | - |
Tritrichomonas suis | xanthosine 5'-phosphate + NADH | - |
? | |
inosine 5'-phosphate + NAD+ + H2O | rate-limiting step of the de novo guanine nucleotide biosynthesis | Tritrichomonas suis | xanthosine 5'-phosphate + NADH | - |
? |
Synonyms | Comment | Organism |
---|---|---|
IMPDH | - |
Tritrichomonas suis |
inosine 5'-monophosphate dehydrogenase | - |
Tritrichomonas suis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Tritrichomonas suis |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
1.4 | - |
NAD+ | pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl | Tritrichomonas suis | |
1.4 | - |
inosine 5'-phosphate | pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl | Tritrichomonas suis | |
1.9 | - |
NAD+ | pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl | Tritrichomonas suis | |
1.9 | - |
inosine 5'-phosphate | pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl | Tritrichomonas suis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Tritrichomonas suis |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | NAD+ promotes the nucleophilic attack of Cys319 on IMP, the NAD+ site may be an exploitable target for the design of antimicrobial drugs | Tritrichomonas suis |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
2.9 | - |
NAD+ | pH 8.0, 25°C, recombinant alphabeta core domain, in presence of 100 mM KCl | Tritrichomonas suis | |
6.8 | - |
NAD+ | pH 8.0, 25°C, recombinant full-length enzyme, in presence of 100 mM KCl | Tritrichomonas suis |