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Literature summary for 1.1.1.205 extracted from

  • Hedstrom, L.
    IMP dehydrogenase: Structure, mechanism, and inhibition (2009), Chem. Rev., 109, 2903-2928.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development IMPDH2 is the major target for cancer chemotherapy Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
-
Cricetulus griseus
-
Escherichia coli
-
Pyrococcus horikoshii
-
Toxoplasma gondii
-
Streptococcus pyogenes
-
Pneumocystis carinii
-
Borreliella burgdorferi
expressed in Escherichia coli Homo sapiens
expressed in Escherichia coli Tritrichomonas suis
expressed in Escherichia coli Cryptosporidium parvum

Crystallization (Commentary)

Crystallization (Comment) Organism
tetramer structure of IMPDH shows square planar geometry Streptococcus pyogenes

Protein Variants

Protein Variants Comment Organism
D226N IMPDH1 polymorphism, which is associated with retinal degeneration Homo sapiens
D301N IMPDH1 polymorphism, which does not affect protein function Homo sapiens
G324D IMPDH1 polymorphism, which does not affect protein function Homo sapiens
G519R IMPDH1 polymorphism, which does not affect protein function Homo sapiens
H296R IMPDH1 polymorphism, which does not affect protein function Homo sapiens
H372P IMPDH1 polymorphism, which is associated with retinal degeneration Homo sapiens
L263F IMPDH2 polymorphism, which decreases the value of kcat by a factor of 10 Homo sapiens
N198K IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis Homo sapiens
R105W IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis Homo sapiens
R224P IMPDH1 polymorphism, which is associated with retinal degeneration Homo sapiens
R231P IMPDH1 polymorphism, which causes autosomal dominant retinitis pigmentosa Homo sapiens
T116M IMPDH1 polymorphism, which is associated with retinal degeneration Homo sapiens
V268I IMPDH1 polymorphism, which is associated with retinal degeneration Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
Homo sapiens
1,4-dimethyl-6-nitro-2H-cyclopenta[d]pyridazine
-
Homo sapiens
1-(benzyloxy)-3-(3-pyridin-4-yl-1H-indol-6-yl)urea
-
Homo sapiens
1-methyl-6-[(5-phenyl-1,3-oxazol-2-yl)amino]-1H-indole-3-carbonitrile
-
Homo sapiens
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate binds in the nicotinamide subsite and does not interact with ADP Cryptosporidium parvum
2-(1-benzothiophen-3-yl)-6-methoxy-5-(1,3-oxazol-5-yl)-1H-indole-3-carbaldehyde
-
Homo sapiens
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide antagonizes ADP binding Cryptosporidium parvum
2-[2-(Z)-fluorovinyl]-inosine 5'-phosphate is a time-dependent inactivator Escherichia coli
2-[methyl[2-(2-[[3-(1,3-oxazol-5-yl)-1H-indol-6-yl]amino]-1,3-oxazol-5-yl)phenyl]amino]-2-oxoethyl acetate
-
Homo sapiens
2264A inhibits lymphocyte proliferation; inhibits lymphocyte proliferation Homo sapiens
2264B inhibits lymphocyte proliferation; inhibits lymphocyte proliferation Homo sapiens
3-hydrogenkwadaphnin
-
Homo sapiens
4-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-6-phenyl-1,3,5-triazin-2-ol
-
Homo sapiens
5-bromoisoquinolin-6-amine
-
Homo sapiens
5-chloro-1,4-dimethyl-2H-cyclopenta[d]pyridazine-6-carbonitrile
-
Homo sapiens
6,6'-oxydi(1,4-dihydroquinoxaline-2,3-dione) binds in the nicotinamide subsite and does not interact with ADP Cryptosporidium parvum
6-chloroinosine 5'-phosphate
-
Homo sapiens
6-Cl-IMP
-
Klebsiella aerogenes
7-methoxy-2-(3-methylphenyl)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
Homo sapiens
7-methoxy-6-(1,3-oxazol-5-yl)-3-(2-pyridin-4-ylethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
-
Homo sapiens
ADP
-
Cryptosporidium parvum
ADP
-
Homo sapiens
ADP binds in the adenosine portion, tiazofurin and ADP are strongly synergistic inhibitors, a conformational change occurs upon the binding of one inhibitor that increases the affinity of the second inhibitor Tritrichomonas suis
AVN944 induces caspase-independent apoptosis in multiple myeloma cell lines and displays antiproliferative activity against both androgen-dependent and androgen-independent prostate cancer cell lines; induces caspase-independent apoptosis in multiple myeloma cell lines and displays antiproliferative activity against both androgen-dependent and androgen-independent prostate cancer cell lines Homo sapiens
benzamide riboside displays skeletal muscle toxicity in preclinical trials, which limits its utility; displays skeletal muscle toxicity in preclinical trials, which limits its utility Homo sapiens
beta-difluoromethylene-tiazofurin
-
Homo sapiens
beta-methylene-tiazofurin
-
Homo sapiens
blastadin 11
-
Homo sapiens
EAD
-
Escherichia coli
EICARMP
-
Escherichia coli
EICARMP
-
Homo sapiens
eicosadienoic acid competitive inhibitor versus IMPDH; competitive inhibitor versus IMPDH Homo sapiens
ethyl 9-oxo-9,10-dihydroacridine-1-carboxylate
-
Homo sapiens
FFAD
-
Homo sapiens
halicyclamine A
-
Homo sapiens
helenalin
-
Homo sapiens
imidazo[4,5-e][1,4]diazapine fat base nucleotide, inosine 5'-phosphate but not NAD+ protects against inhibition Escherichia coli
imidazo[4,5-e][1,4]diazapine fat base nucleotide, inosine 5'-phosphate but not NAD+ protects against inhibition; fat base nucleotide, inosine 5'-phosphate but not NAD+ protects against inhibition Homo sapiens
Li+
-
Borreliella burgdorferi
Li+
-
Escherichia coli
linoleic acid
-
Homo sapiens
merimepodib has immunosuppressive activity; has immunosuppressive activity Homo sapiens
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate antagonizes ADP binding Cryptosporidium parvum
mizoribine
-
Candida albicans
mizoribine
-
Eimeria tenella
mizoribine
-
Escherichia coli
mizoribine
-
Homo sapiens
mizoribine
-
Leishmania donovani
mizoribine
-
Plasmodium falciparum
mizoribine
-
Staphylococcus aureus
mizoribine
-
Tritrichomonas suis
mizoribine
-
Trypanosoma brucei
additional information IMPDH2 interacts with protein kinase B/Akt via its plekstrin homology domain, the resulting phosphorylation reduces activity Homo sapiens
additional information becomes resistant to IMPDH inhibitors by rearranging its purine salvage pathways to rely on xanthine instead of hypoxanthine Tritrichomonas suis
Mycophenolic acid
-
Candida albicans
Mycophenolic acid
-
Eimeria tenella
Mycophenolic acid
-
Homo sapiens
Mycophenolic acid
-
Leishmania donovani
Mycophenolic acid
-
Plasmodium falciparum
Mycophenolic acid
-
Staphylococcus aureus
Mycophenolic acid
-
Tritrichomonas suis
Mycophenolic acid
-
Trypanosoma brucei
N-(4-chlorophenyl)-2-phenoxypropanamide antagonizes ADP binding Cryptosporidium parvum
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide binds in the nicotinamide subsite and does not interact with ADP Cryptosporidium parvum
N-(4-methoxyphenyl)-2-naphthalen-1-ylacetamide binds in the nicotinamide subsite and does not interact with ADP Cryptosporidium parvum
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide binds in the nicotinamide subsite and does not interact with ADP Cryptosporidium parvum
N-(5-phenyl-1,3-oxazol-2-yl)isoquinolin-6-amine
-
Homo sapiens
N-[(Z)-(pyridin-3-ylimino)methyl]-2,3-dihydro-1,4-benzodioxine-2-carboxamide
-
Cryptosporidium parvum
N-[1-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]-1-methylethyl]-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide
-
Homo sapiens
N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-2-morpholin-4-ylacetamide
-
Homo sapiens
N-[2-(hydroxymethyl)cyclopentyl]-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]propanediamide
-
Homo sapiens
Na+
-
Borreliella burgdorferi
Na+
-
Escherichia coli
pellynic acid
-
Homo sapiens
phenyl N'-cyano-N-(3-[cyano[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamimidamido]benzyl)imidocarbamate
-
Homo sapiens
ribavirin
-
Homo sapiens
ribavirin
-
Tritrichomonas suis
Selenazofurin
-
Homo sapiens
SFAD
-
Homo sapiens
tert-butyl methyl (1S,4S)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1'H-spiro[cyclopentane-1,2'-quinazoline]-3,4-dicarboxylate
-
Homo sapiens
TFAD
-
Homo sapiens
tiazofurin
-
Cryptosporidium parvum
tiazofurin
-
Homo sapiens
tiazofurin binds in the nicotinamide portion of the dinucleotide site, tiazofurin and ADP are strongly synergistic inhibitors, a conformational change occurs upon the binding of one inhibitor that increases the affinity of the second inhibitor Tritrichomonas suis
VX-148 has immunosuppressive activity; has immunosuppressive activity Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Cs+ activates Escherichia coli
Cs+ activates Borreliella burgdorferi
K+
-
Streptococcus pyogenes
K+ activates Escherichia coli
K+ activates Homo sapiens
K+ activates Tritrichomonas suis
K+ activates Borreliella burgdorferi
additional information Li+ has no effect on activity of IMPDH2 Homo sapiens
additional information Na+ has no effect on activity Cryptosporidium parvum
Na+ activates Homo sapiens
Na+ activates Tritrichomonas suis
NH4+ activates Escherichia coli
NH4+ activates Homo sapiens
NH4+ activates Borreliella burgdorferi
Rb+ activates Homo sapiens
Tl+ activates Homo sapiens

Organism

Organism UniProt Comment Textmining
Borreliella burgdorferi P49058
-
-
Candida albicans
-
-
-
Cricetulus griseus
-
Chinese hamster type 2
-
Cryptosporidium parvum Q8T6T2
-
-
Eimeria tenella
-
-
-
Escherichia coli
-
-
-
Homo sapiens P12268
-
-
Homo sapiens P20839
-
-
Klebsiella aerogenes
-
-
-
Leishmania donovani P21620
-
-
no activity in Giardia lamblia
-
-
-
no activity in Trichomonas vaginalis
-
-
-
Plasmodium falciparum
-
-
-
Pneumocystis carinii Q12658
-
-
Pyrococcus horikoshii
-
-
-
Staphylococcus aureus
-
-
-
Streptococcus pyogenes P0C0H6
-
-
Toxoplasma gondii
-
-
-
Tritrichomonas suis P50097
-
-
Trypanosoma brucei P50098
-
-

Source Tissue

Source Tissue Comment Organism Textmining
myeloma cell
-
Homo sapiens
-
peripheral blood mononuclear cell
-
Homo sapiens
-
prostate cancer cell
-
Homo sapiens
-
retina
-
Homo sapiens
-
retina IMPDH1 predominates in the adult retina Homo sapiens
-
spleen
-
Homo sapiens
-

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
-
Staphylococcus aureus xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Escherichia coli xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Klebsiella aerogenes xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Candida albicans xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Plasmodium falciparum xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Eimeria tenella xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Pyrococcus horikoshii xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Homo sapiens xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Tritrichomonas suis xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Cryptosporidium parvum xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Leishmania donovani xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Trypanosoma brucei xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Streptococcus pyogenes xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Pneumocystis carinii xanthosine 5'-phosphate + NADH + H+
-
?
inosine 5'-phosphate + NAD+ + H2O
-
Borreliella burgdorferi xanthosine 5'-phosphate + NADH + H+
-
?
additional information the CBS subdomain of IMPDH coordinately regulates the adenine and guanine nucleotide pool Escherichia coli ?
-
?

Subunits

Subunits Comment Organism
tetramer crystallography Streptococcus pyogenes

Synonyms

Synonyms Comment Organism
IMPDH
-
Cricetulus griseus
IMPDH
-
Staphylococcus aureus
IMPDH
-
Escherichia coli
IMPDH
-
Klebsiella aerogenes
IMPDH
-
Candida albicans
IMPDH
-
Plasmodium falciparum
IMPDH
-
Eimeria tenella
IMPDH
-
Pyrococcus horikoshii
IMPDH
-
Toxoplasma gondii
IMPDH
-
Tritrichomonas suis
IMPDH
-
Cryptosporidium parvum
IMPDH
-
Leishmania donovani
IMPDH
-
Trypanosoma brucei
IMPDH
-
Streptococcus pyogenes
IMPDH
-
Pneumocystis carinii
IMPDH
-
Borreliella burgdorferi
IMPDH1
-
Homo sapiens
IMPDH2
-
Homo sapiens
inosine 5'-monophosphate dehydrogenase
-
Cricetulus griseus
inosine 5'-monophosphate dehydrogenase
-
Staphylococcus aureus
inosine 5'-monophosphate dehydrogenase
-
Escherichia coli
inosine 5'-monophosphate dehydrogenase
-
Klebsiella aerogenes
inosine 5'-monophosphate dehydrogenase
-
Candida albicans
inosine 5'-monophosphate dehydrogenase
-
Plasmodium falciparum
inosine 5'-monophosphate dehydrogenase
-
Eimeria tenella
inosine 5'-monophosphate dehydrogenase
-
Pyrococcus horikoshii
inosine 5'-monophosphate dehydrogenase
-
Toxoplasma gondii
inosine 5'-monophosphate dehydrogenase
-
Homo sapiens
inosine 5'-monophosphate dehydrogenase
-
Tritrichomonas suis
inosine 5'-monophosphate dehydrogenase
-
Cryptosporidium parvum
inosine 5'-monophosphate dehydrogenase
-
Leishmania donovani
inosine 5'-monophosphate dehydrogenase
-
Trypanosoma brucei
inosine 5'-monophosphate dehydrogenase
-
Streptococcus pyogenes
inosine 5'-monophosphate dehydrogenase
-
Pneumocystis carinii
inosine 5'-monophosphate dehydrogenase
-
Borreliella burgdorferi

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Cricetulus griseus
NAD+
-
Staphylococcus aureus
NAD+
-
Escherichia coli
NAD+
-
Klebsiella aerogenes
NAD+
-
Candida albicans
NAD+
-
Plasmodium falciparum
NAD+
-
Eimeria tenella
NAD+
-
Pyrococcus horikoshii
NAD+
-
Homo sapiens
NAD+
-
Tritrichomonas suis
NAD+
-
Cryptosporidium parvum
NAD+
-
Leishmania donovani
NAD+
-
Trypanosoma brucei
NAD+
-
Streptococcus pyogenes
NAD+
-
Pneumocystis carinii
NAD+
-
Borreliella burgdorferi

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0000005
-
mizoribine
-
Escherichia coli
0.000001
-
imidazo[4,5-e][1,4]diazapine
-
Homo sapiens
0.000006
-
VX-148
-
Homo sapiens
0.000006
-
AVN944
-
Homo sapiens
0.000007
-
merimepodib
-
Homo sapiens
0.000008
-
mizoribine
-
Homo sapiens
0.000014
-
VX-148
-
Homo sapiens
0.00002
-
Selenazofurin with inosine 5'-phosphate as substrate Homo sapiens
0.00003
-
Selenazofurin with inosine 5'-phosphate as substrate Homo sapiens
0.00005
-
imidazo[4,5-e][1,4]diazapine IMPDH2 Escherichia coli
0.00043
-
tiazofurin with inosine 5'-phosphate as substrate Homo sapiens
0.00043
-
TFAD with inosine 5'-phosphate as substrate Homo sapiens
0.00058
-
SFAD with inosine 5'-phosphate as substrate Homo sapiens
0.0007
-
tiazofurin with inosine 5'-phosphate as substrate Homo sapiens
0.0007
-
TFAD with inosine 5'-phosphate as substrate Homo sapiens
0.001
-
2-[2-(Z)-fluorovinyl]-inosine 5'-phosphate
-
Escherichia coli
0.0011
-
SFAD with inosine 5'-phosphate as substrate Homo sapiens
0.002
-
EICARMP
-
Escherichia coli
0.003
-
eicosadienoic acid
-
Homo sapiens
0.016
-
EICARMP
-
Homo sapiens
0.027
-
EAD
-
Escherichia coli
0.038
-
FFAD with inosine 5'-phosphate as substrate Homo sapiens
0.056
-
FFAD with inosine 5'-phosphate as substrate Homo sapiens
0.078
-
6-chloroinosine 5'-phosphate
-
Homo sapiens
0.26
-
6-Cl-IMP
-
Klebsiella aerogenes
1.3
-
tiazofurin
-
Homo sapiens
1.5
-
tiazofurin
-
Cryptosporidium parvum
8.8
-
ADP
-
Homo sapiens
31
-
ADP
-
Tritrichomonas suis
42
-
ADP
-
Cryptosporidium parvum
50
-
tiazofurin
-
Tritrichomonas suis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000005
-
-
Homo sapiens 7-methoxy-2-(3-methylphenyl)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
0.000005
-
-
Homo sapiens N-(5-phenyl-1,3-oxazol-2-yl)isoquinolin-6-amine
0.000007
-
-
Homo sapiens 2-[methyl[2-(2-[[3-(1,3-oxazol-5-yl)-1H-indol-6-yl]amino]-1,3-oxazol-5-yl)phenyl]amino]-2-oxoethyl acetate
0.000012
-
-
Homo sapiens N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-2-morpholin-4-ylacetamide
0.000013
-
-
Homo sapiens 7-methoxy-6-(1,3-oxazol-5-yl)-3-(2-pyridin-4-ylethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
0.000016
-
-
Homo sapiens phenyl N'-cyano-N-(3-[cyano[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamimidamido]benzyl)imidocarbamate
0.000017
-
-
Homo sapiens N-[1-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]-1-methylethyl]-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide
0.000018
-
-
Homo sapiens 4-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-6-phenyl-1,3,5-triazin-2-ol
0.000018
-
-
Homo sapiens N-[2-(hydroxymethyl)cyclopentyl]-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]propanediamide
0.000028
-
-
Homo sapiens (2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
0.00003
-
-
Homo sapiens 2-(1-benzothiophen-3-yl)-6-methoxy-5-(1,3-oxazol-5-yl)-1H-indole-3-carbaldehyde
0.000033
-
-
Homo sapiens 1-methyl-6-[(5-phenyl-1,3-oxazol-2-yl)amino]-1H-indole-3-carbonitrile
0.000035
-
-
Homo sapiens tert-butyl methyl (1S,4S)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1'H-spiro[cyclopentane-1,2'-quinazoline]-3,4-dicarboxylate
0.000076
-
-
Homo sapiens 1-(benzyloxy)-3-(3-pyridin-4-yl-1H-indol-6-yl)urea
0.0005
-
-
Homo sapiens 5-bromoisoquinolin-6-amine
0.00073
-
-
Homo sapiens ethyl 9-oxo-9,10-dihydroacridine-1-carboxylate
0.00076
-
-
Homo sapiens 5-chloro-1,4-dimethyl-2H-cyclopenta[d]pyridazine-6-carbonitrile
0.001
-
-
Homo sapiens pellynic acid
0.0019
-
-
Homo sapiens 1,4-dimethyl-6-nitro-2H-cyclopenta[d]pyridazine
0.07
-
-
Homo sapiens 2264A

General Information

General Information Comment Organism
physiological function mutations in the CBS subdomain of IMPDH1 account for 2-3% of autosomal dominant retinitis pigmentosa Homo sapiens