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Information on EC 1.1.1.205 - IMP dehydrogenase and Organism(s) Cryptosporidium parvum and UniProt Accession Q8T6T2
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1.1.1.205 IMP dehydrogenaseIUBMB Comments
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
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Word Map
- 1.1.1.205
-
mycophenolic
- purine
- guanine
- mofetil
- ribavirin
- leukemia
- tiazofurin
-
rejection
- xmp
-
pharmacodynamic
-
salvage
- hypoxanthine
-
cyclosporine
-
allograft
-
prodrugs
- mizoribine
- phosphoribosyltransferase
- ribonucleotide
- xanthosine
-
guanylate
- tad
- calcineurin
- dgtp
- adenylosuccinate
- 6-mercaptopurine
- dihydrofolate
-
hypoxanthine-guanine
- cryptosporidium
- tacrolimus
- thiopurine
- riboside
- azathioprine
- glucuronide
- parvum
- benzamide
- pigmentosa
- sirolimus
- 6-thioguanine
- analysis
- rbv
-
amido
- cryptosporidiosis
-
c-nucleoside
- tritrichomonas
-
enteric-coated
-
predose
- hgprt
- pharmacology
- diagnostics
- drug development
- medicine
The taxonomic range for the selected organisms is: Cryptosporidium parvum
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
impdh, imp dehydrogenase, inosine monophosphate dehydrogenase, impdh2, impdh1, inosine 5'-monophosphate dehydrogenase, inosine-5'-monophosphate dehydrogenase, impdh ii, imp dh, inosinate dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dehydrogenase, inosinate
-
-
-
-
IMP dehydrogenase
-
-
-
-
IMP oxidoreductase
-
-
-
-
IMPD
-
-
-
-
IMPDH
inosinate dehydrogenase
-
-
-
-
inosine 5'-monophosphate dehydrogenase
inosine monophosphate dehydrogenase
inosine monophosphate oxidoreductase
-
-
-
-
inosine-5'-phosphate dehydrogenase
-
-
-
-
inosinic acid dehydrogenase
-
-
-
-
Raspberry protein
-
-
-
-
SOI12
-
-
-
-
Superoxide-inducible protein 12
-
-
-
-
IMPDH
-
-
-
-
inosine 5'-monophosphate dehydrogenase
-
-
-
-
inosine monophosphate dehydrogenase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
IMP:NAD+ oxidoreductase
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
CAS REGISTRY NUMBER
COMMENTARY
9028-93-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
-
-
-
?
inosine 5'-phosphate + 3-acetylpyridine adenine dinucleotide + H2O
xanthosine 5'-phosphate + reduced 3-acetylpyridine adenine dinucleotide
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
-
-
-
?
inosine 5'-phosphate + acetylpyridine adenine dinucleotide + H2O
xanthosine 5'-phosphate + reduced acetylpyridine adenine dinucleotide
-
-
-
-
?
additional information
?
-
-
the enzyme does not hydrolyze oxanosine monophosphate
-
-
-
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
-
IMPDH catalyzes a dehydrogenase reaction and a hydrolysis reaction, a redox step producing NADH and the covalent intermediate E-xanthosine 5'-monophosphate and a hydrolysis step that produces xanthosine 5'-monophosphate. The enzyme toggles between the open conformation required for the dehydrogenase reaction and the closed conformation of the hydrolase reaction by moving a mobile flap into the NAD site. The dehydrogenase and hydrolase reactions display significant differences in the host (Homo sapiens) and parasite (Cryptosporidium parvum) enzymes, in keeping with the phylogenetic and structural divergence of their active sites
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-[(1-naphthyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
competitive versus NAD+
(2S)-2-[(3,4-dichlorophenyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
competitive versus NAD+, displays excellent IMPDH inhibitory activity and moderate stability in mouse liver microsomes
1-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)-3-quinolin-7-ylurea
displays high potency against Cryptosporidium parvum IMPDH, more than 1000fold selectivity versus human IMPDH type 2 and good stability in mouse liver microsomes
1-(4-chloro-5-nitrocyclohexa-1,5-dien-1-yl)-3-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)urea
displays high potency against Cryptosporidium parvum IMPDH, more than 1000fold selectivity versus human IMPDH type 2 and good stability in mouse liver microsomes
1-[2-[3-(prop-1-en-2-yl)phenyl]propan-2-yl]-3-quinolin-7-ylurea
displays high potency against Cryptosporidium parvum IMPDH, more than 1000fold selectivity versus human IMPDH type 2 and good stability in mouse liver microsomes
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
binds in the nicotinamide subsite and does not interact with ADP
2-[(3,4-dichlorophenyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
racemic variant, competitive versus NAD+. Compound displays good antiparasitic activity in a Toxoplasma gondii strain that relies on Cryptosporidium parvum IMPDH, EC50 20 nM. No toxicity is observed against four mammalian cells lines
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
antagonizes ADP binding
6,6'-oxydi(1,4-dihydroquinoxaline-2,3-dione)
binds in the nicotinamide subsite and does not interact with ADP
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
antagonizes ADP binding
N-(2,3-dichlorophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
poor inhibition of human IMPDH2
N-(2-{3-[(1E)-N-(2-aminoethoxy)ethanimidoyl]phenyl}propan-2-yl)-N'-(4-chloro-3-nitrophenyl)urea
an inhibitor with in vivo anticryptosporidial activity, binding structure determination and analysi, P131 contains two aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while the second interacts with the aromatic ring of a tyrosine in the adjacent subunit. In addition, the amine and NO2 moieties bind in hydrated cavities, forming water-mediated hydrogen bonds to the proteins. The oxime group of P131 lies across the hypoxanthine ring of IMP, while the N5 amine forms hydrogen bonds to the main chain carbonyl O atom of Gly212 and N3 of IMP in all of the subunits
N-(4-chloro-3-methoxyphenyl)-2-(4-oxo[1]benzopyrano[4,3-c]pyrazol-1(4H)-yl)acetamide
-
N-(4-chlorophenyl)-2-phenoxypropanamide
antagonizes ADP binding
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
N-(4-methoxyphenyl)-2-naphthalen-1-ylacetamide
binds in the nicotinamide subsite and does not interact with ADP
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
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
poor inhibition of human IMPDH2
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
poor inhibition of human IMPDH2
N-[(Z)-(pyridin-3-ylimino)methyl]-2,3-dihydro-1,4-benzodioxine-2-carboxamide
-
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
noncompetitive with respect to NAD+, displays submicromolar activity in a Toxoplasma gondii model of Cryptosporidium parvum infection and displays good stability in mouse liver microsome. No antiparasitic activity is observed in mouse with once per day oral dosing of 250 mg/kg for 7 days
(2E)-N-(4-chlorophenyl)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)but-2-enamide
-
-
(2R)-2-[(naphthalen-1-yl)oxy]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
-
Q21
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[4-(trifluoromethyl)phenyl]hex-4-enamide
-
-
(4E)-N-(2,3-dichlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
-
(4E)-N-(3,4-dichlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
-
(4E)-N-(4-chloro-3-methoxyphenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
-
(4E)-N-(4-chlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
-
(4E)-N-(4-chlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-N,4-dimethylhex-4-enamide
-
-
(4E)-N-(4-cyanophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
-
(4E)-N-(4-fluorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
-
(4E)-N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4,6-dimethoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
-
(4E)-N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
-
2-oxo-4-(trifluoromethyl)-2H-1-benzopyran-7-yl 5-methylquinoline-8-sulfonate
-
ZINC46542062
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
-
3-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)propyl (4-chlorophenyl)carbamate
-
-
5,6,7,8-tetrahydroquinoxalin-6-yl 8-methylquinoline-5-sulfonate
-
ZINC89780094
5-([[2-([1,1'-biphenyl]-3-yl)propan-2-yl]carbamoyl]amino)-2-chlorobenzamide
-
-
N-(2-[3-[(1E)-N-(2-aminoethoxy)ethanimidoyl]phenyl[propan-2-yl)-N'-(4-chloro-3-nitrophenyl)urea
-
P131
N-(2-{3-[(1E)-N-(2-aminoethoxy)ethanimidoyl]phenyl}propan-2-yl)-N'-(4-chloro-3-nitrophenyl)urea
-
P131
N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
-
-
N-(4-chloro-3-methoxyphenyl)-2-(4-oxo[1]benzopyrano[4,3-c]pyrazol-1(4H)-yl)acetamide
-
-
N-(4-chlorophenyl)-2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
-
-
N-(4-chlorophenyl)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)butanamide
-
-
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
-
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
-
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
-
N-naphthalen-2-yl-N'-[2-[3-(prop-1-en-2-yl)phenyl]propan-2-yl]urea
-
-
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(1R,2S)-2-[(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)methyl]-1-methylcyclopropyl]propanamide
-
-
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(1S,2R)-2-[(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)methyl]-1-methylcyclopropyl]propanamide
-
-
N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhexanamide
-
-
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
-
additional information
-
1,2,3-triazole containing ether IMPDH inhibitors, small alkyl group on the alpha-position of the ether is required, with the (R)-enantiomer significantly more active than the (S)-enantiomer. Electron-withdrawing groups in the 3- and/or 4-positions of the pendent phenyl ring are best, and conversion of the quinoline containing inhibitors to quinoline-N-oxides retains inhibitory activity both in the presence and absence of bovine serum albumin
-
N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
-
N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
crystallization data. Poor inhibition of human IMPDH2
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
K+
the K+ dependence of kcat value derives from the rate of flap closure, which increases by more than 65fold in the presence of K+. When K+ is replaced with a dummy ion, the residues of the K+ binding site relax into ordered secondary structure, creating a barrier to conformational exchange. K+ mobilizes these residues by providing alternate interactions for the main chain carbonyls. So K+ changes the shape of the energy well, shrinking the reaction coordinate by shifting the closed conformation toward the open state
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.19
3-acetylpyridine adenine dinucleotide
presence of 100 mM K+, pH 8.0, 25°C
0.22
3-acetylpyridine adenine dinucleotide
absence of K+, pH 8.0, 25°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.16
3-acetylpyridine adenine dinucleotide
absence of K+, pH 8.0, 25°C
3
3-acetylpyridine adenine dinucleotide
presence of 100 mM K+, pH 8.0, 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000032
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
pH not specified in the publication, temperature not specified in the publication
0.00048
(2E)-N-(4-chlorophenyl)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)but-2-enamide
-
at pH 8.0 and 25°C
0.000151
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[4-(trifluoromethyl)phenyl]hex-4-enamide
-
at pH 8.0 and 25°C
0.000681
(4E)-N-(2,3-dichlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
at pH 8.0 and 25°C
0.000041
(4E)-N-(3,4-dichlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
at pH 8.0 and 25°C
0.000046
(4E)-N-(4-chloro-3-methoxyphenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
at pH 8.0 and 25°C
0.000042
(4E)-N-(4-chlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
at pH 8.0 and 25°C
0.00087
(4E)-N-(4-chlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-N,4-dimethylhex-4-enamide
-
at pH 8.0 and 25°C
0.00011
(4E)-N-(4-cyanophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
at pH 8.0 and 25°C
0.00018
(4E)-N-(4-fluorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
at pH 8.0 and 25°C
0.0017
(4E)-N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4,6-dimethoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
at pH 8.0 and 25°C
0.000016
(4E)-N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
at pH 8.0 and 25°C
0.000405
3-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)propyl (4-chlorophenyl)carbamate
-
at pH 8.0 and 25°C
0.0028
N-(4-chlorophenyl)-2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
-
at pH 8.0 and 25°C
0.00045
N-(4-chlorophenyl)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)butanamide
-
at pH 8.0 and 25°C
0.000066
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(1R,2S)-2-[(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)methyl]-1-methylcyclopropyl]propanamide
-
at pH 8.0 and 25°C
0.00057
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(1S,2R)-2-[(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)methyl]-1-methylcyclopropyl]propanamide
-
at pH 8.0 and 25°C
0.00006
N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhexanamide
-
at pH 8.0 and 25°C
0.0015
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000014
(2S)-2-[(1-naphthyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
Cryptosporidium parvum
pH 8.0, 25°C
0.0000005
(2S)-2-[(3,4-dichlorophenyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
Cryptosporidium parvum
pH 8.0, 25°C
0.0000009
1-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)-3-quinolin-7-ylurea
Cryptosporidium parvum
pH 8.0, 25°C
0.00000066
1-(4-chloro-5-nitrocyclohexa-1,5-dien-1-yl)-3-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)urea
Cryptosporidium parvum
pH 8.0, 25°C
0.0000008
1-[2-[3-(prop-1-en-2-yl)phenyl]propan-2-yl]-3-quinolin-7-ylurea
Cryptosporidium parvum
pH 8.0, 25°C
0.000002
2-[(3,4-dichlorophenyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
Cryptosporidium parvum
pH 8.0, 25°C
0.000018
N-(2,3-dichlorophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
Cryptosporidium parvum
pH not specified in the publication, temperature not specified in the publication
0.000028
N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
Cryptosporidium parvum
pH not specified in the publication, temperature not specified in the publication
0.000008
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
Cryptosporidium parvum
pH not specified in the publication, temperature not specified in the publication
0.000007
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
Cryptosporidium parvum
pH not specified in the publication, temperature not specified in the publication
0.0001
(1H-naphtho[2,3-d]imidazol-2-yl)methyl 4-aminobenzoate
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.0014
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.0009
3-(1H-naphtho[2,3-d]imidazol-2-yl)propyl 4-aminobenzoate
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.000004
5-([[2-([1,1'-biphenyl]-3-yl)propan-2-yl]carbamoyl]amino)-2-chlorobenzamide
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.0016
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.0033
N-(4-chlorophenyl)-2-phenoxypropanamide
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.0054
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.0016
N-(4-methoxyphenyl)-2-(naphthalen-1-yl)acetamide
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.0012
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
Cryptosporidium parvum
-
pH and temperature not specified in the publication
0.0000021
N-naphthalen-2-yl-N'-[2-[3-(prop-1-en-2-yl)phenyl]propan-2-yl]urea
Cryptosporidium parvum
-
pH and temperature not specified in the publication
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
substrate-binding siteinvolving Cys219 and Met302-Gly303, modelling, overview
additional information
-
substrate-binding siteinvolving Cys219 and Met302-Gly303, modelling, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). IMDH_CRYPV
400
0
43081
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
IMPDH is a homotetramer with square-planar symmetry. The four active sites are located near the subunit interfaces. The IMP site is contained within a monomer, and the residues that contact IMP are strongly conserved among all IMPDHs
additional information
-
IMPDH is a homotetramer with square-planar symmetry. The four active sites are located near the subunit interfaces. The IMP site is contained within a monomer, and the residues that contact IMP are strongly conserved among all IMPDHs
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapour diffusion method, to 3.2 A resolution, space group P21212. In complex with inhibitor N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide, to 2.8 A resolution. The thiazole ring of the inhibitor stacks against the purine ring of IMP perpendicularly, and the remainder of the inhibitor extends across the subunit interface into a pocket in the adjacent monomer, where the bromoaniline moiety interacts with Tyr358 from the adjacent subunit. This residue forms a hydrogen-bonding network involving Glu329, Ser354, Thr221, and possibly the amide nitrogen of N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide. Residues Ser22, Pro26, Gly357 of the adjacent subunit and Ala165 form the remainder of the inhibitor binding pocket. With the exception of Thr221, all of these residues are different in human IMPDHs
purified recombinant enzyme in complex with substrate IMP and inhibitor P131, sitting drop vapor diffusion method, mixing of 400 nl of 13.4 mg/ml protein in 20 mM HEPES, pH 8.0, 150 mM KCl, and 1.5 mM TCEP with 400 nl of reservoir solution containing 0.1 M bicine-NaOH, pH 9.0, and 20% PEG 6000, and equilibration against 0.134 ml of reservoir solution, at 16°C, X-ray diffraction structure determination and analysis at 2.053 A resolution, molecular replacement using the structure of CpIMPDH, PDB ID 3ffs, as search model, modelling
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, His6-tag cleavage using recombinant TEV protease, and additional nickel affinity chromatography to remove the protease, the uncut protein and the affinity tag, followed by dialysis
Ni-NTA Sepharose bead chromatography and Superdex 200 gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of N-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3)
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the enzyme IMPDH is a promising target for the treatment of Cryptosporidium infections
drug development
-
1,2,3-triazole IMPDH inhibitors provide new tools for elucidating the role of IMPDH in Cryptosporidium parvum and may serve as potential therapeutics for treating cryptosporidiosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pimkin, M.; Markham, G.
Inosine 5-monophosphate dehydrogenase
Adv. Enzymol. Relat. Areas Mol. Biol.
76
1-53
2009
Klebsiella aerogenes, Borreliella burgdorferi, Saccharomyces cerevisiae, Candida albicans, Cricetulus griseus, Cryptosporidium parvum, Escherichia coli, Homo sapiens, Mus musculus, Streptococcus pyogenes, Tritrichomonas suis
Riera, T.V.; Wang, W.; Josephine, H.R.; Hedstrom, L.
A kinetic alignment of orthologous inosine-5-monophosphate dehydrogenases
Biochemistry
47
8689-8696
2008
Cryptosporidium parvum, Homo sapiens
Hedstrom, L.
IMP dehydrogenase: Structure, mechanism, and inhibition
Chem. Rev.
109
2903-2928
2009
Klebsiella aerogenes, Candida albicans, Cricetulus griseus, Escherichia coli, Eimeria tenella, Staphylococcus aureus, Plasmodium falciparum, Pyrococcus horikoshii, Toxoplasma gondii, no activity in Giardia lamblia, no activity in Trichomonas vaginalis, Streptococcus pyogenes (P0C0H6), Homo sapiens (P12268), Homo sapiens (P20839), Leishmania donovani (P21620), Borreliella burgdorferi (P49058), Tritrichomonas suis (P50097), Trypanosoma brucei (P50098), Pneumocystis carinii (Q12658), Cryptosporidium parvum (Q8T6T2)
Maurya, S.K.; Gollapalli, D.R.; Kirubakaran, S.; Zhang, M.; Johnson, C.R.; Benjamin, N.N.; Hedstrom, L.; Cuny, G.D.
Triazole inhibitors of Cryptosporidium parvum inosine 5-monophosphate dehydrogenase
J. Med. Chem.
52
4623-4630
2009
Cryptosporidium parvum
Macpherson, I.S.; Kirubakaran, S.; Gorla, S.K.; Riera, T.V.; DAquino, J.A.; Zhang, M.; Cuny, G.D.; Hedstrom, L.
The structural basis of Cryptosporidium-specific IMP dehydrogenase inhibitor selectivity
J. Am. Chem. Soc.
132
1230-1231
2010
Cryptosporidium parvum (Q8T6T2), Cryptosporidium parvum
Riera, T.V.; Zheng, L.; Josephine, H.R.; Min, D.; Yang, W.; Hedstrom, L.
Allosteric activation via kinetic control: potassium accelerates a conformational change in IMP dehydrogenase
Biochemistry
50
8508-8518
2011
Cryptosporidium parvum (Q8T6T2)
Johnson, C.R.; Gorla, S.K.; Kavitha, M.; Zhang, M.; Liu, X.; Striepen, B.; Mead, J.R.; Cuny, G.D.; Hedstrom, L.
Phthalazinone inhibitors of inosine-5-monophosphate dehydrogenase from Cryptosporidium parvum
Bioorg. Med. Chem. Lett.
23
1004-1007
2013
Cryptosporidium parvum (Q8T6T2), Cryptosporidium parvum
Gorla, S.K.; Kavitha, M.; Zhang, M.; Liu, X.; Sharling, L.; Gollapalli, D.R.; Striepen, B.; Hedstrom, L.; Cuny, G.D.
Selective and potent urea inhibitors of cryptosporidium parvum inosine 5-monophosphate dehydrogenase
J. Med. Chem.
55
7759-7771
2012
Cryptosporidium parvum (Q8T6T2), Cryptosporidium parvum
Gorla, S.K.; Kavitha, M.; Zhang, M.; Chin, J.E.; Liu, X.; Striepen, B.; Makowska-Grzyska, M.; Kim, Y.; Joachimiak, A.; Hedstrom, L.; Cuny, G.D.
Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5-monophosphate dehydrogenase
J. Med. Chem.
56
4028-4043
2013
Cryptosporidium parvum (Q8T6T2), Cryptosporidium parvum
Kim, Y.; Makowska-Grzyska, M.; Gorla, S.K.; Gollapalli, D.R.; Cuny, G.D.; Joachimiak, A.; Hedstrom, L.
Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity
Acta Crystallogr. Sect. F
71
531-538
2015
Cryptosporidium parvum (Q8T6T2), Cryptosporidium parvum, Cryptosporidium parvum Iowa II (Q8T6T2)
Lee, S.; Ku, A.F.; Vippila, M.R.; Wang, Y.; Zhang, M.; Wang, X.; Hedstrom, L.; Cuny, G.D.
Mycophenolic anilides as broad specificity inosine-5-monophosphate dehydrogenase (IMPDH) inhibitors
Bioorg. Med. Chem. Lett.
30
127543
2020
Cryptosporidium parvum, Homo sapiens (P12268), Homo sapiens
Yu, R.; Kim, Y.; Maltseva, N.; Braunstein, P.; Joachimiak, A.; Hedstrom, L.
Oxanosine monophosphate is a covalent inhibitor of inosine 5'-monophosphate dehydrogenase
Chem. Res. Toxicol.
32
456-466
2019
Cryptosporidium parvum, Tritrichomonas foetus, Campylobacter jejuni (A0A2R4D3F6), Bacillus anthracis (A0A6L8P2U9), Homo sapiens (P12268)
Omolabi, K.F.; Iwuchukwu, E.A.; Agoni, C.; Olotu, F.A.; Soliman, M.E.S.
A probable means to an end exploring P131 pharmacophoric scaffold to identify potential inhibitors of Cryptosporidium parvum inosine monophosphate dehydrogenase
J. Mol. Model.
27
35
2021
Cryptosporidium parvum
Juvale, K.; Shaik, A.; Kirubakaran, S.
Inhibitors of inosine 5'-monophosphate dehydrogenase as emerging new generation antimicrobial agents
MedChemComm
10
1290-1301
2019
Bacillus anthracis, Bacillus anthracis (A0A6L8P2U9), Cryptosporidium parvum, Clostridium perfringens (A0A127ELD1), Campylobacter jejuni (A0A2R4D3F6), Mycolicibacterium thermoresistibile (G7CNL4), Mycobacterium tuberculosis (P9WKI7), Listeria monocytogenes (Q926Y9), Pseudomonas aeruginosa (Q9HXM5), Vibrio cholerae (Q9KTW3), Bacillus anthracis Ames, Mycolicibacterium thermoresistibile ATCC 19527 (G7CNL4), Listeria monocytogenes ATCC BAA-679 (Q926Y9), Mycobacterium tuberculosis H37Rv (P9WKI7), Vibrio cholerae ATCC 39315 (Q9KTW3)
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