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Literature summary for 1.1.1.205 extracted from
- Inosine 5-monophosphate dehydrogenase (2009), Adv. Enzymol. Relat. Areas Mol. Biol., 76, 1-53.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | genes IMD2, IMD3 and IMD4 support growth in the absence of guanine | Saccharomyces cerevisiae |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| in complex with inosine 5'-phosphate, at 1.9 A resolution | Streptococcus pyogenes |
| in complex with sulfate, at 2.4 A resolution | Borreliella burgdorferi |
| in complex with xanthosine 5'-phosphate, inhibitor mycophenolic acid and K+, at 2.6 A resolution | Cricetulus griseus |
| type 1 in complex with inhibitor 6-Cl-inosine 5'-phosphate, at 2.6 A resolution, type 2 in complex with inhibitor 6-Cl-inosine 5'-phosphate and SAD or NAD, at 2.9 A resolution, and with inhibitors ribavirin-monophosphate and C2-mycophenolic adenine nucleotide, at 2.65 A resolution | Homo sapiens |
| wild-type at 2.3 A resolution, in complex with xanthosine 5'-phosphate, at 2.6 A resolution, in complex with inhibitor ribavirin-monophosphate, at 1.9 A resolution, in complex with inhibitors ribavirin-monophosphate and mycophenolic acid, at 2.5 A resolution, in complex with inosine 5'-phosphate, at 2.2 A resolution, in complex with inosine 5'-phosphate and inhibitor mycophenolic acid, at 1.95 A resolution, in complex with xanthosine 5'-phosphate and inhibitor mycophenolic acid, at 2.2 A resolution, in complex with xanthosine 5'-phosphate and NAD+, at 2.15 A resolution. Mutant DELTA(101-226) in complex with inosine 5'-phosphate and inhibitor beta-CH2-tiazofurin adenine dinucletoide, at 2.2 A resolution or in complex with inhibitor mizoribine monophosphate, at 2 A resolution | Tritrichomonas suis |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| A251T | is 4fold less sensitive to mycophenolic acid but 40fold more sensitve to mizoribine monophosphate. Mutation does not affect kcat but decreases Km values for both substrates, is catalytically more efficient. Mutation renders the enzyme resistant to NAD+ substrate inhibition, stabilizes the closed conformation, which has opposing effects on enzyme susceptiblities to mycophenolic acid and mizoribine monophosphate | Candida albicans |
| C319S | is essentially inactive, two-step binding process for inosine 5'-phosphate remains | Tritrichomonas suis |
| C331A | mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity | Homo sapiens |
| D13A | is activated by Mg2+ and Ca2+ in lieu of K+ | Escherichia coli |
| D248A | selectively impairs NAD binding | Escherichia coli |
| D338A | affects Kcat more than 600fold and increases the Km for inosine 5'-phosphate, hydride transfer rate is diminished at least 5000fold, rate of inactivation by 6-chloroinosine 5'-phosphate is increased 3fold | Escherichia coli |
| D364A | mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity | Homo sapiens |
| D50A | is inhibited by Mg2+ and Ca2+, Mg2+ inhibition becomes uncompetitive with respect to K+ and competitive with both inosine 5'-phosphate and NAD+, in contrast to the wild-type enzyme, the mutant is inactive in the absence of K+ | Escherichia coli |
| DELTA(101-226) | crystallized in complex with inosine 5'-phosphate and inhibitor beta-CH2-tiazofurin adenine dinucletoide, at 2.2 A resolution or in complex with inhibitor mizoribine monophosphate, at 2 A resolution | Tritrichomonas suis |
| E460A | is activated by Mg2+ and Ca2+ in lieu of K+ | Escherichia coli |
| G326A | mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity | Homo sapiens |
| K409A | mutated type 2 isozyme, low-activity protein with increased Km value | Homo sapiens |
| M70A | mutated type 2 isozyme, low-activity protein with increased Km value | Homo sapiens |
| R418A | decreases steady-state enzymic activity 500fold but presteady burst of NADH production in the first enzyme turnover is unaffected nor is the rate NADH release. Guanidine derivates rescue the mutation, which is attributed to an acceleration of the E-XMP hydrolysis | Tritrichomonas suis |
| R418K | does not impair E-XMP hydrolysis but destabilizes the closed conformation, resulting in a strong enzyme inhibition by NAD and NADH | Tritrichomonas suis |
| R418Q | stabilizes the closed conformation but it is defective in E-XMP hydrolysis | Tritrichomonas suis |
| S329A | mutated type 2 isozyme, increases the Km for both inosine 5'-phosphate and NAD without altering kcat | Homo sapiens |
| Y111A | mutated type 2 isozyme, low-activity protein with increased Km value | Homo sapiens |
| Y419F | decreases steady-state enzymic activity 500fold but presteady burst of NADH production in the first enzyme turnover is unaffected nor is the rate NADH release | Tritrichomonas suis |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 6-chloroinosine 5'-phosphate | - |
Escherichia coli |  |
| 6-chloroinosine 5'-phosphate | - |
Homo sapiens | |
| C2-mycophenolic adenine dinucleotide | - |
Homo sapiens | |
| Ca2+ | competitive inhibition with respect to both K+ and NAD+ | Escherichia coli | |
| imidazo[4,5-e][1,4]diazapine | - |
Escherichia coli | |
| imidazo[4,5-e][1,4]diazapine | - |
Homo sapiens | |
| Li+ | competitive inhibition with respect to both K+ and NAD+ | Escherichia coli | |
| Mg2+ | competitive inhibition with respect to both K+ and NAD+ | Escherichia coli | |
| mizoribine monophosphate | - |
Candida albicans | |
| mizoribine monophosphate | - |
Cryptosporidium parvum | |
| mizoribine monophosphate | - |
Escherichia coli | |
| mizoribine monophosphate | - |
Homo sapiens | |
| mizoribine monophosphate | - |
Streptococcus pyogenes | |
| Mycophenolic acid | - |
Borreliella burgdorferi | |
| Mycophenolic acid | - |
Candida albicans | |
| Mycophenolic acid | - |
Cricetulus griseus | |
| Mycophenolic acid | - |
Cryptosporidium parvum | |
| Mycophenolic acid | - |
Homo sapiens | |
| Mycophenolic acid | IMD2 imparts mycophenolic acid resistance due to A253S as a critical amino acid substitution | Saccharomyces cerevisiae | |
| Mycophenolic acid | - |
Streptococcus pyogenes | |
| Mycophenolic acid | - |
Tritrichomonas suis | |
| Na+ | competitive inhibition with respect to both K+ and NAD+ | Escherichia coli | |
| NAD+ | - |
Candida albicans | |
| NAD+ | - |
Homo sapiens | |
| P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Borreliella burgdorferi | |
| P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Cryptosporidium parvum | |
| P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Escherichia coli | |
| P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Homo sapiens | |
| P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Tritrichomonas suis | |
| ribavirin monophosphate | - |
Cryptosporidium parvum | |
| ribavirin monophosphate | - |
Homo sapiens | |
| ribavirin monophosphate | - |
Streptococcus pyogenes | |
| ribavirin monophosphate | - |
Tritrichomonas suis | |
| selenazole adenine dinucleotide | - |
Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0017 | - |
inosine 5'-phosphate | in the presence of 12 mM K+ | Tritrichomonas suis | |
| 0.0092 | - |
inosine 5'-phosphate | type 2 isozyme, in the presence of 0.39 mM K+ | Homo sapiens | |
| 0.014 | - |
inosine 5'-phosphate | type 1 isozyme, in the presence of 0.65 mM K+ | Homo sapiens | |
| 0.029 | - |
inosine 5'-phosphate | - |
Cryptosporidium parvum | |
| 0.029 | - |
inosine 5'-phosphate | in the presence of 25 mM K+ | Borreliella burgdorferi | |
| 0.032 | - |
NAD+ | type 2 isozyme, in the presence of 0.39 mM K+ | Homo sapiens | |
| 0.042 | - |
NAD+ | type 1 isozyme, in the presence of 0.65 mM K+ | Homo sapiens | |
| 0.06 | - |
inosine 5'-phosphate | in the presence of 2.8 mM K+ | Escherichia coli | |
| 0.062 | - |
inosine 5'-phosphate | - |
Streptococcus pyogenes | |
| 0.15 | - |
NAD+ | - |
Cryptosporidium parvum | |
| 0.15 | - |
NAD+ | in the presence of 12 mM K+ | Tritrichomonas suis | |
| 1.1 | - |
NAD+ | in the presence of 25 mM K+ | Borreliella burgdorferi | |
| 1.18 | - |
NAD+ | - |
Streptococcus pyogenes | |
| 2 | - |
NAD+ | in the presence of 2.8 mM K+ | Escherichia coli | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| K+ | - |
Cricetulus griseus | |
| K+ | - |
Escherichia coli | |
| K+ | - |
Tritrichomonas suis | |
| K+ | - |
Borreliella burgdorferi | |
| K+ | enhances inosine 5'-phosphate bound at a stoichiometry of four sites per tetramer and the affinity of the type 2 isozyme by 2fold | Homo sapiens | |
| additional information | inosine 5'-phosphate binding is not altered by K+ | Klebsiella aerogenes | |
| Na+ | - |
Tritrichomonas suis | |
| Na+ | activates type 2 isozyme | Homo sapiens | |
| NH4+ | activates type 2 isozyme | Homo sapiens | |
| Rb+ | activates type 2 isozyme | Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Borreliella burgdorferi | - |
- |
- |
| Candida albicans | - |
- |
- |
| Cricetulus griseus | - |
hamster type 2 | - |
| Cryptosporidium parvum | - |
- |
- |
| Escherichia coli | - |
- |
- |
| Homo sapiens | - |
- |
- |
| Klebsiella aerogenes | - |
- |
- |
| Mus musculus | - |
- |
- |
| Saccharomyces cerevisiae | - |
- |
- |
| Streptococcus pyogenes | - |
- |
- |
| Tritrichomonas suis | - |
- |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| inosine 5'-phosphate + NAD+ + H2O | - |
Cricetulus griseus | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Escherichia coli | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Homo sapiens | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Cryptosporidium parvum | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Klebsiella aerogenes | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Streptococcus pyogenes | xanthosine 5'-phosphate + NADH + H+ | - |
? | |
| inosine 5'-phosphate + NAD+ + H2O | - |
Candida albicans | 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+ | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| tetramer | - |
Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| IMD2 | - |
Saccharomyces cerevisiae |
| IMD3 | - |
Saccharomyces cerevisiae |
| IMD4 | - |
Saccharomyces cerevisiae |
| IMPDH | - |
Cricetulus griseus |
| IMPDH | - |
Mus musculus |
| IMPDH | - |
Escherichia coli |
| IMPDH | - |
Homo sapiens |
| IMPDH | - |
Saccharomyces cerevisiae |
| IMPDH | - |
Cryptosporidium parvum |
| IMPDH | - |
Klebsiella aerogenes |
| IMPDH | - |
Streptococcus pyogenes |
| IMPDH | - |
Candida albicans |
| IMPDH | - |
Tritrichomonas suis |
| IMPDH | - |
Borreliella burgdorferi |
| inosine 5'-monophosphate dehydrogenase | - |
Cricetulus griseus |
| inosine 5'-monophosphate dehydrogenase | - |
Mus musculus |
| inosine 5'-monophosphate dehydrogenase | - |
Escherichia coli |
| inosine 5'-monophosphate dehydrogenase | - |
Homo sapiens |
| inosine 5'-monophosphate dehydrogenase | - |
Saccharomyces cerevisiae |
| inosine 5'-monophosphate dehydrogenase | - |
Cryptosporidium parvum |
| inosine 5'-monophosphate dehydrogenase | - |
Klebsiella aerogenes |
| inosine 5'-monophosphate dehydrogenase | - |
Streptococcus pyogenes |
| inosine 5'-monophosphate dehydrogenase | - |
Candida albicans |
| inosine 5'-monophosphate dehydrogenase | - |
Tritrichomonas suis |
| inosine 5'-monophosphate dehydrogenase | - |
Borreliella burgdorferi |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 1.4 | - |
inosine 5'-phosphate | type 2 isozyme, in the presence of 0.39 mM K+ | Homo sapiens | |
| 1.8 | - |
inosine 5'-phosphate | type 1 isozyme, in the presence of 0.65 mM K+ | Homo sapiens | |
| 1.9 | - |
inosine 5'-phosphate | in the presence of 12 mM K+ | Tritrichomonas suis | |
| 2.6 | - |
inosine 5'-phosphate | in the presence of 25 mM K+ | Borreliella burgdorferi | |
| 3.3 | - |
inosine 5'-phosphate | - |
Cryptosporidium parvum | |
| 13 | - |
inosine 5'-phosphate | in the presence of 2.8 mM K+ | Escherichia coli | |
| 24 | - |
inosine 5'-phosphate | - |
Streptococcus pyogenes | |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NAD+ | - |
Cricetulus griseus | |
| NAD+ | - |
Escherichia coli | |
| NAD+ | - |
Homo sapiens | |
| NAD+ | - |
Cryptosporidium parvum | |
| NAD+ | - |
Klebsiella aerogenes | |
| NAD+ | - |
Streptococcus pyogenes | |
| NAD+ | - |
Candida albicans | |
| NAD+ | - |
Tritrichomonas suis | |
| NAD+ | - |
Borreliella burgdorferi | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.000065 | - |
ribavirin monophosphate | - |
Tritrichomonas suis | |
| 0.000095 | - |
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | type 1 isozyme | Homo sapiens | |
| 0.00014 | - |
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | type 2 isozyme | Homo sapiens | |
| 0.00039 | - |
ribavirin monophosphate | type 2 isozyme | Homo sapiens | |
| 0.0005 | - |
mizoribine monophosphate | - |
Escherichia coli | |
| 0.0005 | - |
mizoribine monophosphate | - |
Streptococcus pyogenes | |
| 0.00065 | - |
ribavirin monophosphate | type 1 isozyme | Homo sapiens | |
| 0.0011 | - |
Mycophenolic acid | type 1 isozyme | Homo sapiens | |
| 0.0015 | - |
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Cryptosporidium parvum | |
| 0.0016 | - |
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Borreliella burgdorferi | |
| 0.0023 | - |
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Tritrichomonas suis | |
| 0.0039 | - |
mizoribine monophosphate | type 2 isozyme | Homo sapiens | |
| 0.006 | - |
ribavirin monophosphate | - |
Cryptosporidium parvum | |
| 0.006 | - |
ribavirin monophosphate | - |
Streptococcus pyogenes | |
| 0.006 | - |
Mycophenolic acid | type 2 isozyme | Homo sapiens | |
| 0.0082 | - |
mizoribine monophosphate | type 1 isozyme | Homo sapiens | |
| 0.0085 | - |
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate | - |
Escherichia coli | |
| 0.0115 | - |
mizoribine monophosphate | - |
Cryptosporidium parvum | |
| 8 | - |
Mycophenolic acid | - |
Borreliella burgdorferi | |
| 9 | - |
Mycophenolic acid | - |
Tritrichomonas suis | |
| 10 | - |
Mycophenolic acid | - |
Cryptosporidium parvum | |
| 10 | - |
Mycophenolic acid | - |
Streptococcus pyogenes | |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | enhanced expression of the type 2 isozyme in leukemias and other proliferating human cells | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | mice that are homozygotic knockouts for the gene that encodes the type 2 isozyme die in early embryonic stages, despite presumptive expression of a functional type 1 isozyme and purine salvage enzymes | Mus musculus |
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