Any feedback?
Literature summary for 1.1.1.205 extracted from
- Inosine monophosphate dehydrogenase (IMPDH) as a target in drug discovery (2008), Med. Res. Rev., 28, 219-232.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | differences between the human and Mycobacterium tuberculosis IMPDHs in the region of binding of nucleotide inhibitors on the inosine 5'-phosphate binding site. These and other differences, may be exploited for the design of new inhibitors with selectivity against Mycobacterium tuberculosis IMPDH | Mycobacterium tuberculosis |
| drug development | type I IMPDH is identified as an antiangiogenic drug target. Inhibition may cause endothelial cell cycle arrest | Homo sapiens |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| at 2.18 A resolution | Thermotoga maritima |
| at 2.3 A resolution, in complex with inosine 5'-phosphate and beta-methylene-thiazole-4-carboxyamide-adenine dinucleotide at 2.2 A resolution, in complex with xanthosine 5'-phosphate and NAD+ at 2.15 A resolution, in complex with xanthosine 5'-phosphate and mycophenolic acid at 2.2 A resolution, in complex with RVP and mycophenolic acid at 2.15 A resolution, in complex with 4-carbamoyl-1-beta-D-ribofuranosylimidazolium-5-olate-5'-phosphate at 2.0 A resolution | Tritrichomonas suis |
| at 2.4 A resolution | Borreliella burgdorferi |
| in complex with inosine 5'-phosphate and mycophenolic acid at 2.6 A resolution | Cricetulus griseus |
| in complex with inosine 5'-phosphate at 1.9 A resolution | Streptococcus pyogenes |
| in complex with xanthosine 5'-phosphate at 2.1 A resolution | Pyrococcus horikoshii OT3 |
| type I isoform, in complex with 6-chloropurine riboside 5'-monophosphate at 2.5 A resolution | Homo sapiens |
| type II isoform, in complex with 6-chloropurine riboside 5'-monophosphate and selenazole-4-carboxyamide-adenine dinucleotide at 2.9 A resolution, in complex with ribavirin monophosphate and phosphonic acidmono-[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-ethyl] ester at 2.65 resolution, in complex with with 6-chloropurine riboside 5'-monophosphate and NAD+ at 2.9 A resolution | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| benzamide riboside | inhibitory activity is higher than tiazofurin and lower than selenazofurin; inhibitory activity is higher than tiazofurin and lower than selenazofurin | Homo sapiens |  |
| beta-methylene-thiazole-4-carboxyamide-adenine dinucleotide | - |
Tritrichomonas suis | |
| BMS-337197 | is a potent IMPDH inhibitor, shows in vivo activity for inhibition of antibody production in mice | Mus musculus | |
| BMS-337197 | is a potent IMPDH inhibitor, shows in vivo activity for inhibition of antibody production in the adjuvant-induced arthritis model in rats | Rattus norvegicus | |
| Mycophenolic acid | - |
Cricetulus griseus | |
| Mycophenolic acid | - |
Escherichia coli | |
| Mycophenolic acid | is a uncompetitive inhibitor of IMPDH with respect to both inosine 5'-phosphate and NAD+, inhibits IMPDH by trapping the covalent intermediate. It it is easily converted to mycophenolic acid-7-O-glucuronide, which limits the inhibitory efficacy and higher doses are therefore needed in order to maintain appropriate therapeutic levels; is a uncompetitive inhibitor of IMPDH with respect to both inosine 5'-phosphate and NAD+, inhibits IMPDH by trapping the covalent intermediate. It it is easily converted to mycophenolic acid-7-O-glucuronide, which limits the inhibitory efficacy and higher doses are therefore needed in order to maintain appropriate therapeutic levels | Homo sapiens | |
| Mycophenolic acid | - |
Leishmania donovani | |
| Mycophenolic acid | - |
Tritrichomonas suis | |
| NAD+ | - |
Tritrichomonas suis | |
| ribavirin monophosphate | - |
Homo sapiens | |
| ribavirin monophosphate | - |
Mycobacterium tuberculosis | |
| Selenazofurin | - |
Homo sapiens | |
| selenazole-4-carboxyamide-adenine dinucleotide | - |
Homo sapiens | |
| tiazofurin | - |
Homo sapiens | |
| VX-148 | - |
Homo sapiens | |
| VX-497 | - |
Homo sapiens | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 56000 | - |
4 * 56000 | Homo sapiens |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Borreliella burgdorferi | - |
- |
- |
| Cricetulus griseus | - |
chinese hamster | - |
| Escherichia coli | - |
- |
- |
| Homo sapiens | P12268 | - |
- |
| Homo sapiens | P20839 | - |
- |
| Leishmania donovani | - |
- |
- |
| Mus musculus | - |
- |
- |
| Mycobacterium tuberculosis | - |
strains CDC1551 and H37Rv | - |
| Pyrococcus horikoshii OT3 | - |
- |
- |
| Rattus norvegicus | - |
- |
- |
| Streptococcus pyogenes | - |
- |
- |
| Thermotoga maritima | - |
- |
- |
| Tritrichomonas suis | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| carcinoma cell | - |
Homo sapiens | - |
| carcinoma cell | type II isoform predominates | Homo sapiens | - |
| K-562 cell | - |
Homo sapiens | - |
| leukocyte | - |
Homo sapiens | - |
| leukocyte | type I isoform is prevalent | Homo sapiens | - |
| lymphocyte | - |
Homo sapiens | - |
| lymphocyte | type I isoform is prevalent | Homo sapiens | - |
| additional information | type II isoform predominates in proliferating cells and is upregulated in neoplastic cells | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| inosine 5'-phosphate + NAD+ + H2O | - |
Homo sapiens | xanthosine 5'-phosphate + NADH | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Cricetulus griseus | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Mus musculus | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Escherichia coli | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Rattus norvegicus | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Streptococcus pyogenes | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Mycobacterium tuberculosis | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Leishmania donovani | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Thermotoga maritima | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Tritrichomonas suis | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Borreliella burgdorferi | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Pyrococcus horikoshii OT3 | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| tetramer | 4 * 56000 | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| IMPDH | - |
Cricetulus griseus |
| IMPDH | - |
Mus musculus |
| IMPDH | - |
Escherichia coli |
| IMPDH | - |
Rattus norvegicus |
| IMPDH | - |
Streptococcus pyogenes |
| IMPDH | - |
Mycobacterium tuberculosis |
| IMPDH | - |
Leishmania donovani |
| IMPDH | - |
Thermotoga maritima |
| IMPDH | - |
Tritrichomonas suis |
| IMPDH | - |
Borreliella burgdorferi |
| IMPDH | - |
Pyrococcus horikoshii OT3 |
| IMPDH | - |
Homo sapiens |
| inosine monophosphate dehydrogenase | - |
Cricetulus griseus |
| inosine monophosphate dehydrogenase | - |
Mus musculus |
| inosine monophosphate dehydrogenase | - |
Escherichia coli |
| inosine monophosphate dehydrogenase | - |
Rattus norvegicus |
| inosine monophosphate dehydrogenase | - |
Streptococcus pyogenes |
| inosine monophosphate dehydrogenase | - |
Mycobacterium tuberculosis |
| inosine monophosphate dehydrogenase | - |
Leishmania donovani |
| inosine monophosphate dehydrogenase | - |
Thermotoga maritima |
| inosine monophosphate dehydrogenase | - |
Tritrichomonas suis |
| inosine monophosphate dehydrogenase | - |
Borreliella burgdorferi |
| inosine monophosphate dehydrogenase | - |
Pyrococcus horikoshii OT3 |
| inosine monophosphate dehydrogenase | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NAD+ | - |
Mycobacterium tuberculosis | |
| NAD+ | dependent on | Cricetulus griseus | |
| NAD+ | dependent on | Mus musculus | |
| NAD+ | dependent on | Escherichia coli | |
| NAD+ | dependent on | Rattus norvegicus | |
| NAD+ | dependent on | Streptococcus pyogenes | |
| NAD+ | dependent on | Leishmania donovani | |
| NAD+ | dependent on | Thermotoga maritima | |
| NAD+ | dependent on | Tritrichomonas suis | |
| NAD+ | dependent on | Borreliella burgdorferi | |
| NAD+ | dependent on | Pyrococcus horikoshii OT3 | |
| NAD+ | dependent on | Homo sapiens | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0000002 | - |
Mycophenolic acid | - |
Leishmania donovani | |
| 0.000007 | - |
Mycophenolic acid | against type II isoform | Homo sapiens | |
| 0.000007 | - |
VX-497 | type I isoform | Homo sapiens | |
| 0.000009 | - |
Mycophenolic acid | - |
Tritrichomonas suis | |
| 0.00001 | - |
VX-497 | against type II isoform | Homo sapiens | |
| 0.00002 | - |
Mycophenolic acid | - |
Escherichia coli | |
| 0.00002 | - |
Mycophenolic acid | against IMPDH in general | Homo sapiens | |
| 0.000033 | - |
Mycophenolic acid | type I isoform | Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Cricetulus griseus |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Escherichia coli |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Rattus norvegicus |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Streptococcus pyogenes |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Leishmania donovani |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Thermotoga maritima |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Tritrichomonas suis |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Borreliella burgdorferi |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Pyrococcus horikoshii OT3 |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides | Homo sapiens |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides. Loss of both alleles of the type 2 gene results in very early embryonic lethality. Type I enzymatic activity appears not to be essential for normal mouse development or fertility | Mus musculus |
| physiological function | is a key enzyme in the biosynthesis of purine nucleotides. Mutations in the type I gene cause the RP10 form of autosomal dominant retinitis pigmentosa | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
